Sample records for allyl alcohol cyclization

  1. Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds. (United States)

    Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming


    A novel and efficient tandem SN2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc)3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

  2. Synthesis of 3-Allyl-4-phosphachromones by Cyclized Coupling of Ethyl o-Hydroxyphenyl(ethynyl)phosphinate with Allyl Bromide

    Institute of Scientific and Technical Information of China (English)


    3-Allyl-4-phosphachromones as the phosphorus analogues of chromone were firstly prepared in good yields and high regioselectivity by the palladium(Ⅱ)-catalyzed cyclized coupling reaction of ethyl o-hydroxyphenyl(ethynyl)-phosphinate with allyl bromide.

  3. Fe(Ⅲ)催化的烯丙醇的Friedel-Crafts环化反应合成多取代茚%Synthesis of Multisubstituted Indenes by Fe(Ⅲ)-Catalyzed Friedel-Crafts Cyclization of Allylic Alcohols

    Institute of Scientific and Technical Information of China (English)

    张继坦; 张金花; 方旷; 束官莹; 谢美华


    在FeCl3·6H2O催化下,多取代的烯丙醇可以顺利进行分子内Friedel-Crafts环化反应,以中等到优良的产率得到一系列多取代茚化合物,该反应操作简单、反应条件温和.产物结构经IR,1H NMR,13C NMR,HR MS及X射线单晶衍射分析确证.%FeCl3·6H2O-catalyzed intramolecular Friedel-Crafts cyclization of multisubstituted allylic alcohols proceeded smoothly and a series of multisubstituted indenes were synthesized in moderate to high yields. The reaction has the advantages of simple manipulation and mild reaction conditions. The products were characterized by IR, 'H NMR, 13C NMR, HR MS and X-ray diffraction analysis.

  4. Palladium-catalyzed amination of allyl alcohols. (United States)

    Ghosh, Raju; Sarkar, Amitabha


    An efficient catalytic amination of aryl-substituted allylic alcohols has been developed. The complex [(η(3)-allyl)PdCl](2) modified by a bis phosphine ligand, L, has been used as catalyst in the reaction that afforded a wide range of allyl amines in good to excellent yield under mild conditions.

  5. Compound list: allyl alcohol [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available allyl alcohol AA 00010 ftp:/.../ ...

  6. Cp*Co(III)-Catalyzed Dehydrative C-H Allylation of 6-Arylpurines and Aromatic Amides Using Allyl Alcohols in Fluorinated Alcohols. (United States)

    Bunno, Youka; Murakami, Nanami; Suzuki, Yudai; Kanai, Motomu; Yoshino, Tatsuhiko; Matsunaga, Shigeki


    Cp*Co(III)-catalyzed C-H allylation of various aromatic C-H bonds using allyl alcohols as allylating reagents is described. Improved reaction conditions using fluorinated alcohol solvents afforded efficient directed C-H allylation of 6-arylpurines, benzamides, and a synthetically useful Weinreb amide with good functional group compatibility.

  7. Regio- and Stereospecific Formation of Protected Allylic Alcohols via Zirconium-Mediated SN2' Substitution of Allylic Chlorides


    Fox, Richard J; Lalic, Gojko; Bergman, Robert G.


    A new, highly regio- and stereospecific SN2' substitution reaction between a zirconium oxo complex and allylic chloride has been achieved. The resulting allylic alcohol or TBS-protected allylic ether products were isolated in good to excellent yields with a wide range of E-allylic chlorides. A mechanism for the SN2' allylic substitution consistent with kinetic, stereochemical and secondary isotope effect studies was proposed.

  8. Amination of allylic alcohols in water at room temperature. (United States)

    Nishikata, Takashi; Lipshutz, Bruce H


    The "trick" to carrying out regiocontrolled aminations of allylic alcohols in water as the only medium is use of a nanomicelle's interior as the organic reaction solvent. When HCO(2)Me is present, along with the proper base and source of catalytic Pd, allylic amines are cleanly formed at room temperature.

  9. Direct activation of allylic alcohols in palladium catalyzed coupling reactions


    Gümrükçü, Y.


    The direct use of allylic alcohols in substitution reactions without pre-activation of the hydroxyl-group into a better leaving group or the use of additional stoichiometric in situ activators remains challenging due to the poor leaving group ability of the hydroxyl-group. Hence, it is important to develop new methods to activate (bio-mass derived) allyl-alcohols, which allow ‘green’ chemical processes for a broad substrate range. This may have a considerable impact on the methodology for fin...

  10. The magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group and its application to a highly stereoselective synthesis of (+/-)-matatabiether. Allylmagnesium compounds by reductive magnesiation of allyl phenyl sulfides. (United States)

    Cheng, D; Zhu, S; Yu, Z; Cohen, T


    The first example of a magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group is demonstrated by a highly stereoselective synthesis of the bicyclic terpene matatabiether 10. The synthetic method is particularly valuable, not only because of the stereochemical control and the utility of the versatile hydroxyl group introduced into the product, but also because the precursor of the allylmagnesium is an allyl phenyl sulfide, which is more stable and more easily prepared in a connective fashion than the usual allyl halide precursor. Since the presence of lithium ions encourages undesirable proton transfer to the cyclized organometallic and is detrimental to the stereochemical control, the conversion of the allylic thioether to the allylmagnesium utilizes a lithium-free method involving direct reductive magnesiation in the presence of the magnesium-anthracene complex.

  11. Direct activation of allylic alcohols in palladium catalyzed coupling reactions

    NARCIS (Netherlands)

    Gümrükçü, Y.


    The direct use of allylic alcohols in substitution reactions without pre-activation of the hydroxyl-group into a better leaving group or the use of additional stoichiometric in situ activators remains challenging due to the poor leaving group ability of the hydroxyl-group. Hence, it is important to

  12. Radiation initiated copolymerization of allyl alcohol with acrylonitrile

    Energy Technology Data Exchange (ETDEWEB)

    Solpan, Dilek; Guven, Olgun [Hacettepe Univ., Ankara (Turkey). Dept. of Chemistry


    Copolymerization of allyl alcohol (AA) with acrylonitrile (AN) initiated by {gamma}-rays has been investigated to determine the respective reactivity ratios. Three different experimental techniques, namely Fourier Transform Infrared (FTIR), Ultraviolet (UV/vis) and elemental analysis (EA) have been used for the determination of copolymer compositions. Fineman-Ross (FR), Kelen-Tudos (KT), Non-Linear Least Square (NLLS) Analysis and Q-e methods have been applied to the three sets of experimental data. It has been concluded that data obtained from elemental analysis as applied to the Non-Linear Least Square approach gave the most reliable reactivity ratios as 2.09 and 0.40 for acrylonitrile and allyl alcohol, respectively. (Author).

  13. Radiation initiated copolymerization of allyl alcohol with acrylonitrile (United States)

    Şolpan, Dilek; Güven, Olgun


    Copolymerization of allyl alcohol (AA) with acrylonitrile (AN) initiated by γ-rays has been investigated to determine the respective reactivity ratios. Three different experimental techniques, namely Fourier Transform Infrared (FTIR), Ultraviolet (UV/vis) and elemental analysis (EA) have been used for the determination of copolymer compositions. Fineman-Ross (FR), Kelen-Tüdös (KT), Non-Linear Least Square (NLLS) Analysis and Q-e methods have been applied to the three sets of experimental data. It has been concluded that data obtained from elemental analysis as applied to the Non-Linear Least Square approach gave the most reliable reactivity ratios as 2.09 and 0.40 for acrylonitrile and allyl alcohol, respectively.

  14. A convenient procedure for the synthesis of allyl and benzyl ethers from alcohols and phenols

    Indian Academy of Sciences (India)

    H Surya Prakash Rao; S P Senthilkumar


    Allyl and benzyl ethers of alcohols can be prepared conveniently and in high yield with allyl and benzyl bromide in the presence of solid potassium hydroxide without use of any solvent. Phenols can be converted to allyl ethers but are inert to benzylation under above conditions.

  15. Divergent synthetic routes for ring expansion or cyclization from 1,4-allylic diol derivatives via gold(I) catalysis or zinc(II) mediation. (United States)

    Zhu, Li-Li; Li, Xiao-Xiao; Zhou, Wen; Li, Xin; Chen, Zili


    A new efficient method was developed to transform cyclic alkanols into one-carbon higher homologated ketones using various esters as the leaving groups through gold-catalyzed allylic cation-promoted pinacol-type rearrangement. This reaction, coupled with oxy-Cope rearrangement, provided a new strategy to synthesize five-carbon homologated ring ketones. In addition, using ZnBr(2), 2,5-dihydrofuran products were obtained in moderate to good yields via an intramolecular cyclization process.

  16. Gold(I)-Assisted α-Allylation of Enals and Enones with Alcohols. (United States)

    Mastandrea, Marco Michele; Mellonie, Niall; Giacinto, Pietro; Collado, Alba; Nolan, Steven P; Miscione, Gian Pietro; Bottoni, Andrea; Bandini, Marco


    The intermolecular α-allylation of enals and enones occurs by the condensation of variously substituted allenamides with allylic alcohols. Cooperative catalysis by [Au(ItBu)NTf2] and AgNTf2 enables the synthesis of a range of densely functionalized α-allylated enals, enones, and acyl silanes in good yield under mild reaction conditions. DFT calculations support the role of an α-gold(I) enal/enone as the active nucleophilic species.

  17. A Mechanistic Study of Direct Activation of Allylic Alcohols in Palladium Catalyzed Amination Reactions


    Yasemin Gumrukcu; Bas de Bruin; Reek, Joost N. H.


    We here report a computational approach on the mechanism of allylicamination reactions using allyl-alcohols and amines as the substrates and phosphoramidite palladium catalyst 1a, which operates in the presence of catalytic amount of 1,3-diethylurea as a co-catalyst. DFT calculations showed a cooperative hydrogen-bonding array between the urea moiety and the hydroxyl group of the allyl alcohol, which strengthens the hydrogen bond between the O-H moiety of the coordinated allyl-alcohol and th...

  18. Selective epoxidation of allylic alcohols with a titania-silica aerogel

    Energy Technology Data Exchange (ETDEWEB)

    Dusi, M.; Mallat, T.; Baiker, A. [Lab. of Technical Chemistry, Swiss Federal Inst. of Technology, ETH-Zentrum, Zuerich (Switzerland)


    An amorphous mesoporous titania-silica aerogel (20 wt%TiO{sub 2} - 80 wt% SiO{sub 2}) and tert.-butylhydroperoxide (TBHP) have been used for the epoxidation of various allylic alcohols. Allylic alcohols possessing an internal double bond were more reactive than those with a terminal C=C bond. Epoxide selectivities could be improved by addition of (basic) zeolite 4 A and NaHCO{sub 3} to the reaction mixture. (orig.)

  19. Direct use of allylic alcohols for platinum-catalyzed monoallylation of amines. (United States)

    Utsunomiya, Masaru; Miyamoto, Yoshiki; Ipposhi, Junji; Ohshima, Takashi; Mashima, Kazushi


    A new direct catalytic amination of allylic alcohols promoted by the combination of platinum and a large bite-angle ligand DPEphos was developed in which the allylic alcohol was effectively converted to a pi-allylplatinum intermediate without the use of an activating reagent. The use of the DPEphos ligand was essential for obtaining high catalyst activity and high monoallylation selectivity of primary amines, allowing the formation of a variety of monoallylation products in good to excellent yield.

  20. Cyclization by intramolecular carbolithiation of alkyl- and vinyllithiums prepared by the action of aromatic radical anions on phenyl thioethers. High stereoselectivity in the cyclization accelerated by an allylic lithium oxyanion. (United States)

    Deng, Kai; Bensari-Bouguerra, Ahlem; Whetstone, Joseph; Cohen, Theodore


    The reductive lithiation of alkyl and vinyl phenyl thioethers by aromatic radical anions is shown to be the most general method yet known for preparing organolithiums capable of intramolecular carbometalation of unactivated alkenes to produce five-membered rings and in one case a four-membered ring (in a far higher yield than known cases). The relative rates of cyclization for alkyllithiums are secondary > tertiary > primary, and the yields are very high. In the secondary case, the stereoselectivity is extremely high, producing a cyclopentylmethyllithium with a trans-2-alkyl substituent. A remarkable finding is that for all of the organolithiums a lithium oxyanionic group in the proximal allylic position to the alkene greatly accelerates the cyclization and leads almost exclusively to a trans relationship between the CH(2)Li group and the OLi group, the opposite relationship from that observed in intramolecular carbolithiations by allyllithiums. A mechanistic rationale for this divergence is discussed. One of the two types of proximal homoallylic lithium oxyanions exerts an analogous effect. An intriguing limitation, even occurring with the highly reactive secondary organolithium and in the presence of an allylic oxyanionic group, is the failure of intramolecular carbolithiation when a methyl group is at the terminus of the alkene.

  1. A Mechanistic Study of Direct Activation of Allylic Alcohols in Palladium Catalyzed Amination Reactions

    Directory of Open Access Journals (Sweden)

    Yasemin Gumrukcu


    Full Text Available We here report a computational approach on the mechanism of allylicamination reactions using allyl-alcohols and amines as the substrates and phosphoramidite palladium catalyst 1a, which operates in the presence of catalytic amount of 1,3-diethylurea as a co-catalyst. DFT calculations showed a cooperative hydrogen-bonding array between the urea moiety and the hydroxyl group of the allyl alcohol, which strengthens the hydrogen bond between the O-H moiety of the coordinated allyl-alcohol and the carbonyl-moiety of the ligand. This hydrogen bond pattern facilitates the (rate-limiting C-O oxidative addition step and leads to lower energy isomers throughout the catalytic cycle, clarifying the role of the urea-moiety.

  2. Transient overexpression of adh8a increases allyl alcohol toxicity in zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Nils Klüver

    Full Text Available Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L. Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1 during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos. Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L. Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes

  3. How phenyl makes a difference: mechanistic insights into the ruthenium( ii )-catalysed isomerisation of allylic alcohols

    KAUST Repository

    Manzini, Simone


    [RuCl(η5-3-phenylindenyl)(PPh3)2] (1) has been shown to be a highly active catalyst for the isomerisation of allylic alcohols to the corresponding ketones. A variety of substrates undergo the transformation, typically with 0.25-0.5 mol% of catalyst at room temperature, outperforming commonly-used complexes such as [RuCl(Cp)(PPh3) 2] and [RuCl(η5-indenyl)(PPh3) 2]. Mechanistic experiments and density functional theory have been employed to investigate the mechanism and understand the effect of catalyst structure on reactivity. These investigations suggest a oxo-π-allyl mechanism is in operation, avoiding intermediate ruthenium hydride complexes and leading to a characteristic 1,3-deuterium shift. Important mechanistic insights from DFT and experiments also allowed for the design of a protocol that expands the scope of the transformation to include primary allylic alcohols. © 2013 The Royal Society of Chemistry.

  4. Polystyrene-supported Selenides and Selenoxide:Versatile Routes to Synthesize Allylic Alcohols

    Institute of Scientific and Technical Information of China (English)

    Wei Ming XU; You Chu ZHANG; Xian HUANG


    Several polystyrene-supported selenides and selenoxide have been prepared firstly. These novel reagents were treated with LDA to produce selenium stabilized carbanions, which reacted with aldehydes and alkyl halides, followed by selenoxide syn-elimination and [2,3] sigmatropic rearrangement respectively to give Z-allylic alcohols stereoselectively.

  5. A Mechanistic Study of Direct Activation of Allylic Alcohols in Palladium Catalyzed Amination Reactions

    NARCIS (Netherlands)

    Gumrukcu, Y.; de Bruin, B.; Reek, J.N.H.


    We here report a computational approach on the mechanism of allylicamination reactions using allyl-alcohols and amines as the substrates and phosphoramidite palladium catalyst 1a, which operates in the presence of catalytic amount of 1,3-diethylurea as a co-catalyst. DFT calculations showed a cooper

  6. Cooperative catalysis by palladium and a chiral phosphoric acid: enantioselective amination of racemic allylic alcohols. (United States)

    Banerjee, Debasis; Junge, Kathrin; Beller, Matthias


    Cooperative catalysis by [Pd(dba)2] and the chiral phosphoric acid BA1 in combination with the phosphoramidite ligand L8 enabled the efficient enantioselective amination of racemic allylic alcohols with a variety of functionalized amines. This catalytic protocol is highly regio- and stereoselective (up to e.r. 96:4) and furnishes valuable chiral amines in almost quantitative yield.

  7. The Wacker oxidation of allyl alcohol along cyclic-intermediate routes: An ab initio molecular dynamics investigation (United States)

    Imandi, Venkataramana; Nair, Nisanth N.


    The absence of isotope scrambling observed by Henry and coworkers in the Wacker oxidation of deuterated allylic alcohol was used by them as support for the inner-sphere mechanism hydroxypalladation mechanism. One of the assumptions used to interpret their experimental data was that allyl alcohol oxidation takes place through non-cyclic intermediate routes as in the case of ethene. Here we verify this assumption through ab initio metadynamics simulations of the Wacker oxidation of allyl alcohol in explicit solvent. Importance of our results in interpreting the isotope scrambling experiments is discussed.

  8. Chemoenzymatic one-pot synthesis in an aqueous medium: combination of metal-catalysed allylic alcohol isomerisation-asymmetric bioamination. (United States)

    Ríos-Lombardía, Nicolás; Vidal, Cristian; Cocina, María; Morís, Francisco; García-Álvarez, Joaquín; González-Sabín, Javier


    The ruthenium-catalysed isomerisation of allylic alcohols was coupled, for the first time, with asymmetric bioamination in a one-pot process in an aqueous medium. In the cases involving prochiral ketones, the ω-TA exhibited excellent enantioselectivity, identical to that observed in the single step. As a result, amines were obtained from allylic alcohols with high overall yields and excellent enantiomeric excesses.

  9. Epoxidation of allyl alcohol to glycidol over the microporous TS-1 catalyst. (United States)

    Wróblewska, Agnieszka; Fajdek, Anna


    The results of the epoxidation of allyl alcohol with 30% hydrogen peroxide over the TS-1 catalyst have been presented. The studies were carried out under the atmospheric pressure and at the presence of methanol as a solvent. The influence of the following technological parameters on the course of epoxidation was examined: the temperature of 20-60 degrees C, the molar ratio of AA/H(2)O(2) 1:1-5:1, the methanol concentration of 5-90 wt%, the catalyst content of 0.1-5.0 wt% and the reaction time 5-300 min. The main functions describing the process were the selectivity to glycidol in relation to allyl alcohol consumed, the conversion of substrates, and the selectivity of transformation to organic compounds in relation to hydrogen peroxide consumed. The parameters at which the functions describing the process reached the highest values were determined.

  10. Highly Regioselective Palladium-Catalyzed Carboxylation of Allylic Alcohols with CO2. (United States)

    Mita, Tsuyoshi; Higuchi, Yuki; Sato, Yoshihiro


    Various allylic alcohols were carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using ZnEt2 as a stoichiometric transmetalation agent under a CO2 atmosphere (1 atm). This carboxylation proceeded in a highly regioselective manner to afford branched carboxylic acids predominantly. The β,γ-unsaturated carboxylic acid thus obtained was successfully converted into an optically active γ-butyrolactone, a known intermediate of (R)-baclofen.

  11. Iron(III) chloride catalyzed glycosylation of peracylated sugars with allyl/alkynyl alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Narayanaperumal, Senthil; Silva, Rodrigo Cesar da; Monteiro, Julia L.; Correa, Arlene G.; Paixao, Marcio W., E-mail: [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica


    In this work, the use of ferric chloride as an efficient catalyst in glycosylation reactions of sugars in the presence of allyl and alkynyl alcohols is described. The corresponding glycosides were obtained with moderate to good yields. This new procedure presented greater selectivity when compared to classic methods found in the literature. Principal features of this simple method include non-hazardous reaction conditions, low-catalyst loading, good yields and high anomeric selectivity (author)

  12. Non-thermal plasma destruction of allyl alcohol in waste gas: kinetics and modelling (United States)

    DeVisscher, A.; Dewulf, J.; Van Durme, J.; Leys, C.; Morent, R.; Van Langenhove, H.


    Non-thermal plasma treatment is a promising technique for the destruction of volatile organic compounds in waste gas. A relatively unexplored technique is the atmospheric negative dc multi-pin-to-plate glow discharge. This paper reports experimental results of allyl alcohol degradation and ozone production in this type of plasma. A new model was developed to describe these processes quantitatively. The model contains a detailed chemical degradation scheme, and describes the physics of the plasma by assuming that the fraction of electrons that takes part in chemical reactions is an exponential function of the reduced field. The model captured the experimental kinetic data to less than 2 ppm standard deviation.

  13. Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study. (United States)

    Barker, Graeme; Johnson, David G; Young, Paul C; Macgregor, Stuart A; Lee, Ai-Lan


    Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au-allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive.

  14. Nickel-catalyzed enantioselective hydrovinylation of silyl-protected allylic alcohols:An efficient access to homoallylic alcohols with a chiral quaternary center

    Institute of Scientific and Technical Information of China (English)


    Asymmetric hydrovinylation of silyl-protected allylic alcohols catalyzed by nickel complexes of chiral spiro phosphoramidite ligands was developed.A series of homoallylic alcohols with a chiral quaternary center were produced in high yields(up to 97%) and high enantioselectivities(up to 95% ee).The reaction provides an efficient method for preparing bifunctional compounds with a chiral quaternary carbon center.

  15. Direct Nucleophilic Substitution of Free Allylic Alcohols in Water Catalyzed by FeCl3⋅6 H2O: Which is the Real Catalyst?


    Trillo Alarcón, María Paz; Baeza, Alejandro; Nájera Domingo, Carmen


    The allylic substitution reaction, and particularly the direct allylic amination reaction, of free allylic alcohols in water catalyzed by FeCl3⋅6 H2O is described. This novel environmentally-friendly methodology allows the use of a wide variety of nitrogenated nucleophiles such as sulfonamides, carbamates, benzamides, anilines, benzotriazoles, and azides, generally giving good yields of the corresponding substitution products. The synthetic applicability of the process is also demonstrated be...

  16. Epoxidation of olefins and allylic alcohols with hydrogen peroxide catalyzed by heteropoly acids in the presence of cetylpyridinium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Okabayashi, Takuji; Yamawaki, Kazumasa; Nishihara, Hideki; Yamada, Hiroshi; Ura, Toshikazu; Ishii, Yasutaka; Ogawa, Masaya


    The epoxidation of olefins and allylic alcohols with aqueous hydrogen peroxide could be achieved in good yield when 12-tungustophosphoric acid(WPA) was used with two phase condition using chloroform as the solvent. From the epoxidation result by 12-molybdophosphoric acid(MPA) and WPA catalysts, epoxidation activity of WPA catalyst was found to be remarkably higher than that of MPA. The rate of epoxidation by heteropoly acids catalyst depended markedly upon the activity of the reaction medium. Epoxidation of allylic alcohols with hydrogen peroxide proceeded under mild conditions, resulting good yield of epoxi-alcohols. Epoxidation of olefins by WPA/cetylpyridium chloride was confirmed to be promoted selectively with cheap and pure hydrogen peroxide, resulting good yield. (3 figs, 2 tabs, 18 refs)

  17. Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls (United States)

    Liang, Tao; Zhang, Wandi; Chen, Te-Yu; Nguyen, Khoa D.; Krische, Michael J.


    The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo- and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k and 6m, respectively. Primary alcohols 2a, 2l and 2p were converted to the siloxy-crotylation products 3a, 3l and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes. PMID:26418572

  18. Fluorinated alcohols as promoters for the metal-free direct substitution reaction of allylic alcohols with nitrogenated, silylated, and carbon nucleophiles. (United States)

    Trillo, Paz; Baeza, Alejandro; Nájera, Carmen


    The direct allylic substitution reaction using allylic alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) as reaction media is described. The developed procedure is simple, works under mild conditions (rt, 50 and 70 °C), and proves to be very general, since different nitrogenated nucleophiles and carbon nucleophiles can be used achieving high yields, especially when HFIP is employed as solvent and aromatic allylic alcohols are the substrates. Thus, sulfonamides, carbamates, carboxamides, and amines can be successfully employed as nitrogen-based nucleophiles. Likewise, silylated nucleophiles such as trimethylsilylazide, allyltrimethylsilane, trimethylsilane, and trimethylsilylphenylacetylene give the corresponding allylic substitution products in high yields. Good results for the Friedel-Crafts adducts are also achieved with aromatic compounds (phenol, anisole, indole, and anilines) as nucleophiles. Particularly interesting are the results obtained with electron-rich anilines, which can behave as nitrogenated or carbon nucleophiles depending on their electronic properties and the solvent employed. In addition, 1,3-dicarbonyl compounds (acetylacetone and Meldrum's acid) are also successfully employed as soft carbon nucleophiles. Studies for mechanism elucidation are also reported, pointing toward the existence of carbocationic intermediates and two working reaction pathways for the obtention of the allylic substitution product.

  19. Synthesis of Oxacyclic Scaffolds via Dual Ruthenium Hydride/Brønsted Acid‐Catalyzed Isomerization/Cyclization of Allylic Ethers

    DEFF Research Database (Denmark)

    Ascic, Erhad; Ohm, Ragnhild Gaard; Petersen, Rico;


    A ruthenium hydride/Brønsted acid‐catalyzed tandem sequence is reported for the synthesis of 1,3,4,9‐tetrahydropyrano[3,4‐b]indoles (THPIs) and related oxacyclic scaffolds. The process was designed on the premise that readily available allylic ethers would undergo sequential isomerization, first ...

  20. Platinum-catalyzed direct amination of allylic alcohols under mild conditions: ligand and microwave effects, substrate scope, and mechanistic study. (United States)

    Ohshima, Takashi; Miyamoto, Yoshiki; Ipposhi, Junji; Nakahara, Yasuhito; Utsunomiya, Masaru; Mashima, Kazushi


    Transition metal-catalyzed amination of allylic compounds via a pi-allylmetal intermediate is a powerful and useful method for synthesizing allylamines. Direct catalytic substitution of allylic alcohols, which forms water as the sole coproduct, has recently attracted attention for its environmental and economical advantages. Here, we describe the development of a versatile direct catalytic amination of both aryl- and alkyl-substituted allylic alcohols with various amines using Pt-Xantphos and Pt-DPEphos catalyst systems, which allows for the selective synthesis of various monoallylamines, such as the biologically active compounds Naftifine and Flunarizine, in good to high yield without need for an activator. The choice of the ligand was crucial toward achieving high catalytic activity, and we demonstrated that not only the large bite-angle but also the linker oxygen atom of the Xantphos and DPEphos ligands was highly important. In addition, microwave heating dramatically affected the catalyst activity and considerably decreased the reaction time compared with conventional heating. Furthermore, several mechanistic investigations, including (1)H and (31)P{(1)H} NMR studies; isolation and characterization of several catalytic intermediates, Pt(xantphos)Cl(2), Pt(eta(2)-C(3)H(5)OH)(xantphos), etc; confirmation of the structure of [Pt(eta(3)-allyl)(xantphos)]OTf by X-ray crystallographic analysis; and crossover experiments, suggested that formation of the pi-allylplatinum complex through the elimination of water is an irreversible rate-determining step and that the other processes in the catalytic cycle are reversible, even at room temperature.

  1. A configurational switch based on iridium-catalyzed allylic cyclization: application in asymmetric total syntheses of prosopis, dendrobate, and spruce alkaloids. (United States)

    Gnamm, Christian; Brödner, Kerstin; Krauter, Caroline M; Helmchen, Günter


    A method for the stereoselective synthesis of 2,6-disubstituted piperidines has been developed that is based on the use of an intramolecular iridium-catalyzed allylic substitution as a configurational switch. The procedure allows the preparation of 2-vinylpiperidines with enantiomeric excesses (ee) of greater than 99%. As applications, total syntheses of piperidine alkaloids have been elaborated, most often by using Ru-catalyzed cross-metatheses as a key step for introduction of a side chain. Asymmetric total syntheses of the prosopis alkaloids (+)-prosopinine, (+)-prosophylline, (+)-prosopine, and of the dendrobate alkaloid (+)-241D and its C6 epimer are described.

  2. The utilization of the mesoporous Ti-SBA-15 catalyst in the epoxidation of allyl alcohol to glycidol and diglycidyl ether in the water medium

    Directory of Open Access Journals (Sweden)

    Wróblewska Agnieszka


    Full Text Available This work presents the studies on the optimization the process of allyl alcohol epoxidation over the Ti-SBA-15 catalyst. The optimization was carried out in an aqueous medium, wherein water was introduced into the reaction medium with an oxidizing agent (30 wt% aqueous solution of hydrogen peroxide and it was formed in the reaction medium during the processes. The main investigated technological parameters were: the temperature, the molar ratio of allyl alcohol/hydrogen peroxide, the catalyst content and the reaction time. The main functions the process were: the selectivity of transformation to glycidol in relation to allyl alcohol consumed, the selectivity of transformation to diglycidyl ether in relation to allyl alcohol consumed, the conversion of allyl alcohol and the selectivity of transformation to organic compounds in relation to hydrogen peroxide consumed. The analysis of the layer drawings showed that in water solution it is best to conduct allyl alcohol epoxidation in direction of glycidol (selectivity of glycidol 54 mol% at: the temperature of 10–17°C, the molar ratio of reactants 0.5–1.9, the catalyst content 2.9–4.0 wt%, the reaction time 2.7–3.0 h and in direction of diglycidyl ether (selectivity of diglycidyl ether 16 mol% at: the temperature of 18–33°C, the molar ratio of reactants 0.9–1.65, the catalyst content 2.0–3.4 wt%, the reaction time 1.7–2.6 h. The presented method allows to obtain two very valuable intermediates for the organic industry.

  3. Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols. (United States)

    Durán-Peña, M J; Flores-Giubi, M E; Botubol-Ares, J M; Harwood, L M; Collado, I G; Macías-Sánchez, A J; Hernández-Galán, R


    The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane.

  4. Exciton Coupling in Circular Dichroic Spectroscopy as a Tool for Establishing the Absolute Configuration of alpha,beta-Unsaturated Esters of Allylic Alcohols

    DEFF Research Database (Denmark)

    Lauridsen, A.; Cornett, Claus; Christensen, S. B.


    alpha-beta-Unsaturated esters of allylic alcohols have been shown to exhibit exciton coupling by circular dichroic spectroscopy. This coupling permits the establishment of the absolute configuration. The method was used to prove the absolute configuration at C-2 of archangelolide. Detailed NMR sp...

  5. Allylation of Aromatic Aldehyde under Microwave Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Yu-Mei; JIA,Xue-Feng; WANG,Jin-Xian


    @@ Allylation of carbonyl compounds is one of the most interesting processes for the preparation of homoallylic alcohols. Over the past few decades, many reagents have been developed for such reactions[1~3]. In this paper, we first report allylic zinc reagent 1, which can be prepared from zinc dust and allyl bromide conveniently in THF, and reacted with aromatic aldehyde to give homo-allylic alcohols under microwave irradiation.

  6. Improved synthesis of cyclic tertiary allylic alcohols by asymmetric 1,2-addition of AlMe3 to enones. (United States)

    Kolb, Andreas; Zuo, Wei; Siewert, Jürgen; Harms, Klaus; von Zezschwitz, Paultheo


    The development of an improved protocol for the enantioselective Rh(I) /binap-catalysed 1,2-addition of AlMe3 to cyclic enones is reported. (31)P NMR analysis of the reaction revealed that the catalyst in its resting state is a chloride-bridged dimer. This insight led to the use of AgBF4 as an additive for in situ activation of the dimeric precatalyst. Thus, the catalyst loading can now be reduced to only 1 mol% with respect to rhodium. Various 5-7-membered cyclic enones can be transformed into tertiary allylic alcohols with excellent levels of enantioselectivity and high yields. The obtained products are versatile synthetic building blocks, shown by a highly enantioselective formal total synthesis of the pheromone (-)-frontalin as well as formation of a bicyclic lactone that has the core structure of the natural flavour component "wine lactone".

  7. Stereochemistry of Pd(II)-Catalyzed THF Ring Formation of ε-Hydroxy Allylic Alcohols and Synthesis of 2,3,5-Trisubstituted and 2,3,4,5-Tetrasubstituted Tetrahydrofurans. (United States)

    Murata, Yuki; Uenishi, Jun'ichi


    Pd(II)-catalyzed ring formation of 2,3,5-trisubstituted and 2,3,4,5-tetrasubstituted tetrahydrofurans is described. Oxypalladation of a chiral ε-hydroxy allylic alcohol provides a 5-alkenyltetrahydrofuran ring in excellent yields via a 5-exo-trigonal process. Nine substrates including six secondary allylic alcohols and three primary allylic alcohols with or without an additional secondary hydroxy substituent at the γ-position have been examined. Their structures are restricted by a 2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocane ring. The stereochemistry of the resulting tetrahydrofuran products was determined by chemical transformation. The reaction mechanism is discussed on the basis of the stereochemical results. The steps in the chiral allylic alcohol directed or the nucleophilic alcohol directed facial selection for the formation of the alkene-Pd(II)-π-complex, the cis-oxypalladation, and a syn-elimination mechanism account for the observed stereochemistry of the reaction.

  8. Facile coupling of propargylic, allylic and benzylic alcohols with allylsilane and alkynylsilane, and their deoxygenation with Et3SiH, catalyzed by Bi(OTf)3 in [BMIM][BF4] ionic liquid (IL), with recycling and reuse of the IL. (United States)

    Kumar, G G K S Narayana; Laali, Kenneth K


    Allyltrimethylsilane (allyl-TMS) reacts with propargylic alcohols 1a-1d in the presence of 10% Bi(OTf)(3) in [BMIM][BF(4)] solvent to furnish the corresponding 1,5-enynes in respectable isolated yields (87-93%) at room temperature. The utility of Bi(OTf)(3) as a superior catalyst was demonstrated in a survey study on coupling of allyl-TMS with employing several metallic triflates (Bi, Ln, Al, Yb) as well as, B(C(6)F(5))(3), Zn(NTf(2))(2) and Bi(NO(3))(3)·5H(2)O. Coupling of cyclopropyl substituted propargylic alcohol with allyl-TMS gave the skeletally intact 1,5-enyne and a ring opened derivative as a mixture. Coupling of propargylic/allylic alcohol with allyl-TMS resulted in allylation at both benzylic (2 isomers) and propargylic positions, as major and minor products respectively. The scope of this methodology for allylation of a series of allylic and benzylic alcohols was explored. Chemoselective reduction of a host of propargylic, propagylic/allylic, bis-allylic, allylic, and benzylic alcohols with Et(3)SiH was achieved in high yields with short reaction times. The same approach was successfully applied to couple representative propargylic and allylic alcohols with 1-phenyl-2-trimethylsilylacetylene. The recovery and reuse of the ionic liquid (IL) was gauged in a case study with minimal decrease in isolated yields after six cycles.

  9. Mesoporous sol-gel WO{sub 3} thin films via poly(styrene-co-allyl-alcohol) copolymer templates

    Energy Technology Data Exchange (ETDEWEB)

    Ozkan Zayim, Esra [Department of Physics, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul 80626 (Turkey); Liu, Ping; Lee, Se-Hee; Tracy, C. Edwin; Pitts, J. Roland; Deb, Satyen K. [National Renewable Energy Laboratory, Golden, CO 80401 (United States); Turner, John A.


    In this study a copolymer poly(styrene-co-allyl-alcohol), [-CH{sub 2}CH(C{sub 6}H{sub 5})-]{sub x}[-CH{sub 2}CH-(CH{sub 2}OH)-]{sub y} has been employed as a novel template in a sol-gel synthesis process to direct the formation of mesoporous tungsten oxide. The copolymer, due to its rigid hydrophobic block of polystyrene, is a more effective surfactant in an alcohol solution than polypropylene oxide-polyethylene oxide based compounds. The films have been prepared by a spin-coating technique from an ethanol solution of tungsten hexachloride. At room temperature, ultraviolet illumination method has been found to be very suitable for removing the polymer template, leading to the formation of a high-quality mesoporous structure. The electrochromic and optical properties of the mesoporous films are described and compared to standard sol-gel tungsten oxide films. Mesoporous materials exhibit superior high-rate ion-insertion performance when used as electrochromic layers.

  10. Structure and stability of acrolein and allyl alcohol networks on Ag(111) from density functional theory based calculations with dispersion corrections (United States)

    Ferullo, Ricardo M.; Branda, Maria Marta; Illas, Francesc


    The interaction of acrolein and allyl alcohol with the Ag(111) surface has been studied by means of periodic density functional theory based calculations including explicitly dispersion terms. Different coverage values have been explored going from isolated adsorbed molecules to isolated dimers, interacting dimers or ordered overlayers. The inclusion of the dispersion terms largely affects the calculated values of the adsorption energy and also the distance between adsorbed molecule and the metallic surface but much less the adsorbate-adsorbate interactions. Owing to the large dipole moment of acrolein, the present calculations predict that at high coverage this molecule forms a stable extensive two-dimensional network on the surface, caused by the alignment of the adsorbate dipoles. For the case of allyl alcohol, dimers and complex networks exhibit similar stability.

  11. Structure formation of soil dispersions in the presence of polyelectrolytes on the basis of allyl alcohol and acryl acid derivatives

    Directory of Open Access Journals (Sweden)

    Amankait Asanov


    Full Text Available Some changes of structural composition and surface properties of soil dispersions in the presence of polyelectrolytes, based on allyl alcohol and acryl acid derivatives, have been studied. The results show, that the changes in the structure of soil dispersions composition are connected with the added concentration and pH value, that depend on mole ratio and nature of functional groups, as well as on the nature of counterions and concomitant electrolytes, changing with the conditions of polymer analogous conversion and neutralization reaction. Experimental data show, that the change in the conformational state and the length of the macromolecule has a significant impact on the structure-forming effect and the amount of polyelectrolyte, needed to achieve the same degree of structure-forming effect of soil dispersions. The causes for the revealed reasons are shown on the basis of the results of the experiment. Along with this, it was found that particular changes of structural composition and surface properties of the soil dispersions depend on the type and concentration of the added polyelectrolyte.

  12. Enantiodivergent Fluorination of Allylic Alcohols: Data Set Design Reveals Structural Interplay between Achiral Directing Group and Chiral Anion. (United States)

    Neel, Andrew J; Milo, Anat; Sigman, Matthew S; Toste, F Dean


    Enantioselectivity values represent relative rate measurements that are sensitive to the structural features of the substrates and catalysts interacting to produce them. Therefore, well-designed enantioselectivity data sets are information rich and can provide key insights regarding specific molecular interactions. However, if the mechanism for enantioselection varies throughout a data set, these values cannot be easily compared. This premise, which is the crux of free energy relationships, exposes a challenging issue of identifying mechanistic breaks within multivariate correlations. Herein, we describe an approach to addressing this problem in the context of a chiral phosphoric acid catalyzed fluorination of allylic alcohols using aryl boronic acids as transient directing groups. By designing a data set in which both the phosphoric and boronic acid structures were systematically varied, key enantioselectivity outliers were identified and analyzed. A mechanistic study was executed to reveal the structural origins of these outliers, which was consistent with the presence of several mechanistic regimes within the data set. While 2- and 4-substituted aryl boronic acids favored the (R)-enantiomer with most of the studied catalysts, meta-alkoxy substituted aryl boronic acids resulted in the (S)-enantiomer when used in combination with certain (R)-phosphoric acids. We propose that this selectivity reversal is the result of a lone pair-π interaction between the substrate ligated boronic acid and the phosphate. On the basis of this proposal, a catalyst system was identified, capable of producing either enantiomer in high enantioselectivity (77% (R)-2 to 92% (S)-2) using the same chiral catalyst by subtly changing the structure of the achiral boronic acid.

  13. A Novel One-Pot and One-Step Microwave-Assisted Cyclization-Methylation Reaction of Amino Alcohols and Acetylated Derivatives with Dimethyl Carbonate and TBAC (United States)

    Ochoa-Terán, Adrián; Guerrero, Leticia; Rivero, Ignacio A.


    A simple and efficient microwave-assisted methodology for the synthesis of 4-substituted-3-methyl-1,3-oxazolidin-2-ones from amino alcohols catalyzed by a ionic liquid was developed. This novel one-pot and one-step cyclization-methylation reaction represents an easier and faster method than any other reported protocols that can be used to obtain the desired products in good yields and high purity. Applying microwave irradiation at 130°C in the presence of TBAC, dimethyl carbonate acts simultaneously as carbonylating and methylating agent and surprisingly promotes an in situ basic trans esterification when a N-acetylated amino alcohol is used as starting material. Furthermore, dimethyl carbonate worked better than diethyl carbonate in performing this reaction. PMID:25692177

  14. Adsorption of acrolein, propanal, and allyl alcohol on Pd(111): a combined infrared reflection-absorption spectroscopy and temperature programmed desorption study. (United States)

    Dostert, Karl-Heinz; O'Brien, Casey P; Mirabella, Francesca; Ivars-Barceló, Francisco; Schauermann, Swetlana


    Atomistic-level understanding of the interaction of α,β-unsaturated aldehydes and their derivatives with late transition metals is of fundamental importance for the rational design of new catalytic materials with the desired selectivity towards C[double bond, length as m-dash]C vs. C[double bond, length as m-dash]O bond partial hydrogenation. In this study, we investigate the interaction of acrolein, and its partial hydrogenation products propanal and allyl alcohol, with Pd(111) as a prototypical system. A combination of infrared reflection-absorption spectroscopy (IRAS) and temperature programmed desorption (TPD) experiments was applied under well-defined ultrahigh vacuum (UHV) conditions to obtain detailed information on the adsorption geometries of acrolein, propanal, and allyl alcohol as a function of coverage. We compare the IR spectra obtained for multilayer coverages, reflecting the molecular structure of unperturbed molecules, with the spectra acquired for sub-monolayer coverages, at which the chemical bonds of the molecules are strongly distorted. Coverage-dependent IR spectra of acrolein on Pd(111) point to the strong changes in the adsorption geometry with increasing acrolein coverage. Acrolein adsorbs with the C[double bond, length as m-dash]C and C[double bond, length as m-dash]O bonds lying parallel to the surface in the low coverage regime and changes its geometry to a more upright orientation with increasing coverage. TPD studies indicate decomposition of the species adsorbed in the sub-monolayer regime upon heating. Similar strong coverage dependence of the IR spectra were found for propanal and allyl alcohol. For all investigated molecules a detailed assignment of vibrational bands is reported.

  15. Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat

    DEFF Research Database (Denmark)

    Tygstrup, N; Jensen, S A; Krog, B


    , doses producing no and about 30% mortality, respectively, within 2 days. In the morning 2, 6, 12, 24, and 36 h after intoxication, RNA was extracted from liver tissue. By slot blot hybridization mRNA levels were determined for acute phase proteins, enzymes involved in ammonia elimination and urea...... synthesis, and for proteins related to liver regeneration. RESULTS: After allyl alcohol, mRNA of "positive" acute phase proteins was higher than after acetaminophen and increased with the dose, whereas after acetaminophen it decreased with the dose. The mRNA of the urea cycle enzymes and glutamine...

  16. Metal-Free α-C(sp3–H Functionalized Oxidative Cyclization of Tertiary N,N-Diaryl Amino Alcohols: Theoretical Approach for Mechanistic Pathway

    Directory of Open Access Journals (Sweden)

    Zakir Ullah


    Full Text Available The mechanistic pathway of TEMPO/I2-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5, four types of reactive species (radical TEMPO, cationic TEMPO, TEMPO-I, and iodo radical, and three types of pathways ((1 SET/PCET mechanism; (2 HAT/1,6-H transfer mechanism; (3 ionic mechanism were assumed. Under the assumption, nine free energy diagrams were acquired through density functional theory calculations. From the comparison of solution-phase free energy, some possible mechanisms were excluded, and then the chosen plausible mechanisms were concretized using the more stable intermediate 7.

  17. Asymmetric Synthesis of Bicyclic Nitrocyclopropanes from Primary Nitro Compounds and Stereoselective Formation of Tetrahydro-2H-cyclopenta[b]furans via Ring Expansion/Cyclization Reaction. (United States)

    Kamimura, Akio; Moriyama, Takaaki; Ito, Yuji; Kawamoto, Takuji; Uno, Hidemitsu


    Optically active bicyclic nitrocyclopropanes are readily prepared from primary chiral nitro compounds, prepared by the conjugate addition of propionaldehyde to a nitro alkene in the presence of proline-derived organocatalysts. The one-step cyclopropanation took place smoothly in a highly stereoselective manner regardless of the stereogenic center adjacent to the allylic unit. Although the allylation reaction catalyzed by BF3·OEt2 provides a mixture of two possible diastereomers, subsequent oxidation of the alcoholic carbon after the formation of nitrocyclopropanes gave diastereomerically pure single products. As a result, separation of the diastereomers during the reaction sequence is unnecessary. Baeyer-Villiger oxidation of the bicyclic nitrocyclopropane ketones followed by enolization resulted in stereoselective formation of a novel cyclopenta[b]furan ring in good yield via ring expansion followed by transannular nucleophilic cyclization.

  18. Highly efficient redox isomerisation of allylic alcohols catalysed by pyrazole-based ruthenium(IV) complexes in water: mechanisms of bifunctional catalysis in water. (United States)

    Bellarosa, Luca; Díez, Josefina; Gimeno, José; Lledós, Agustí; Suárez, Francisco J; Ujaque, Gregori; Vicent, Cristian


    The catalytic activity of ruthenium(IV) ([Ru(η(3):η(3)-C(10)H(16))Cl(2)L]; C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl, L = pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, 3-methyl-5-phenylpyrazole, 2-(1H-pyrazol-3-yl)phenol or indazole) and ruthenium(II) complexes ([Ru(η(6)-arene)Cl(2)(3,5-dimethylpyrazole)]; arene = C(6)H(6), p-cymene or C(6)Me(6)) in the redox isomerisation of allylic alcohols into carbonyl compounds in water is reported. The former show much higher catalytic activity than ruthenium(II) complexes. In particular, a variety of allylic alcohols have been quantitatively isomerised by using [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)] as a catalyst; the reactions proceeded faster in water than in THF, and in the absence of base. The isomerisations of monosubstituted alcohols take place rapidly (10-60 min, turn-over frequency = 750-3000 h(-1)) and, in some cases, at 35 °C in 60 min. The nature of the aqueous species formed in water by this complex has been analysed by ESI-MS. To analyse how an aqueous medium can influence the mechanism of the bifunctional catalytic process, DFT calculations (B3LYP) including one or two explicit water molecules and using the polarisable continuum model have been carried out and provide a valuable insight into the role of water on the activity of the bifunctional catalyst. Several mechanisms have been considered and imply the formation of aqua complexes and their deprotonated species generated from [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)]. Different competitive pathways based on outer-sphere mechanisms, which imply hydrogen-transfer processes, have been analysed. The overall isomerisation implies two hydrogen-transfer steps from the substrate to the catalyst and subsequent transfer back to the substrate. In addition to the conventional Noyori outer-sphere mechanism, which involves the pyrazolide ligand, a new mechanism with a hydroxopyrazole complex as the active species can be at work in water. The


    Directory of Open Access Journals (Sweden)

    Veaceslav Kulciţki


    Full Text Available A review of diterpenoid cyclization initiated by electrophilic reagents is provided. Conventional protonic and Lewis acids are examined along with superacids as initiators of cyclization cascade. An emphasis is placed on the use of cyclization reactions as a tool for the synthesis of compounds with potential practical utility. The review contains 74 references.

  20. Transition metal catalysed Grignard-like allylic activation across tetragonal tin(II) oxide

    Indian Academy of Sciences (India)

    Pradipta Sinha; Moloy Banerjee; Abhijit Kundu; Sujit Roy


    The reaction of allyl halide and a carbonyl compound under the aegis of tetragonal tin(II) oxide and catalytic 8, 10 metal complexes provides the corresponding homoallylic alcohol, via a novel allyl tin intermediate.

  1. Cp*Rh(III)-Catalyzed Low Temperature C-H Allylation of N-Aryl-trichloro Acetimidamide. (United States)

    Debbarma, Suvankar; Bera, Sourav Sekhar; Maji, Modhu Sudan


    The readily synthesized trichloro acetimidamide was found to be an excellent directing group for the directed C-H-allylation reactions. Depending on the allylating agent used, selectively either mono- or diallylated products were readily synthesized. Moreover, the trichloro acetimidamide directing group was found to be highly efficient even at lower temperature for the C-H-allylation reaction. Due to mildness of the reaction conditions, double bond isomerization or cyclization to indole side product was not observed.

  2. Polymer-incarcerated gold-palladium nanoclusters with boron on carbon: a mild and efficient catalyst for the sequential aerobic oxidation-Michael addition of 1,3-dicarbonyl compounds to allylic alcohols. (United States)

    Yoo, Woo-Jin; Miyamura, Hiroyuki; Kobayashi, Shuū


    We have developed a polymer-incarcerated bimetallic Au-Pd nanocluster and boron as a catalyst for the sequential oxidation-addition reaction of 1,3-dicarbonyl compounds with allylic alcohols. The desired tandem reaction products were obtained in good to excellent yields under mild conditions with broad substrate scope. In the course of our studies, we discovered that the excess reducing agent, sodium borohydride, reacts with the polymer backbone to generate an immobilized tetravalent boron catalyst for the Michael reaction. In addition, we found bimetallic Au-Pd nanoclusters to be particularly effective for the aerobic oxidation of allylic alcohols under base- and water-free conditions. The ability to conduct the reaction under relatively neutral and anhydrous conditions proved to be key in maintaining good catalyst activity during recovery and reuse of the catalyst. Structural characterization (STEM, EDS, SEM, and N(2) absorption/desorption isotherm) of the newly prepared PI/CB-Au/Pd/B was performed and compared to PI/CB-Au/Pd. We found that while boron was important for the Michael addition reaction, it was found to alter the structural profile of the polymer-carbon black composite material to negatively affect the allylic oxidation reaction.

  3. Studies on the cyclization reaction of D-aspartic acid

    Institute of Scientific and Technical Information of China (English)

    Yu Chuan Li; Si Ping Pang; Yong Zhong Yu


    The cyclization reaction of D-aspartic acid was studied, the carboxyl groups of D-aspartic acid were protected by benzyl alcohol to give compound D-dibenzyl aspartate. Then (4R)-benzyl azetidine-2-one-4-carboxylate and meso-3,6-disubstituted piperazine2,5-diones were synthesized via intramolecular cyclization and intermolecular cyclization of D-dibenzyl aspartate, respectively, and their structures were confirmed by 1H NMR and MS. Both cyclization reaction conditions were also investigated in detail.

  4. Iodine - catalyzed prins cyclization of aliphatic and aromatic ketones

    Energy Technology Data Exchange (ETDEWEB)

    Kishore, K.R.; Reddy, K.; Silva Junior, Luiz F., E-mail: [Universidade de Sao Paulo (IQ/USP), SP (Brazil). Inst. de Quimica. Dept. de Quimica Fundamental


    Iodine-catalyzed Prins cyclization of homoallylic alcohols and ketones was investigated. Anhydrous conditions and inert atmosphere are not required in this metal-free protocol. The reaction of 2-(3,4-dihydronaphthalene-1-yl)propan-1-ol with six aliphatic symmetric ketones gave the desired products in 67-77% yield. Cyclization was performed with four aliphatic unsymmetric ketones, leading to corresponding pyrans in 66-76% yield. Prins cyclization was also accomplished with four aromatic ketones in 37-66% yield. Finally, Prins cyclization of the monoterpene isopulegol and acetone was successfully achieved. (author)

  5. 丙烯醇催化氨化合成3-甲基吡啶催化剂的制备及性能%Preparation and performance of Zn/H-ZSM-5 catalyst for catalytic amination of allyl alcohol to 3-picoline

    Institute of Scientific and Technical Information of China (English)

    马天奇; 魏天宇; 骈岩杰; 张月成; 赵继全


    采用浸渍法制备了一系列H-ZSM-5分子筛负载过渡金属锌催化剂,在固定床反应器上考察了这些催化剂对丙烯醇催化氨化合成3-甲基吡啶的催化性能。通过对 H-ZSM-5的硅铝比、锌负载量对催化剂催化性能影响的考察,发现硅铝比为80、锌负载量为12%时得到的催化剂Zn12/H-ZSM-5(80)的催化性能最佳。在常压、反应温度420℃、氨醇摩尔比3:1、空速300 h-1条件下,丙烯醇在该催化剂上的转化率和3-甲基吡啶的选择性分别达到97.8%和37.9%。利用X射线衍射(XRD)、X射线光电子能谱(XPS)以及吡啶吸附红外对催化剂进行了表征,结果表明,Zn12/H-ZSM-5(80)上负载的Zn2+为L酸;在丙烯醇生成3-甲基吡啶的反应过程中催化剂的脱氢活性物种为氧化锌,而加成和环合反应则主要是由催化剂中的L酸催化实现的。%H-ZSM-5 supported zinc catalysts were prepared by impregnation method, and their catalytic performances for amination of allyl alcohol to 3-picoline were evaluated in a fixed-bed reactor. It is found that the catalyst Zn12/H-ZSM-5(80) (H-ZSM-5 with 80 silicon/aluminum (Si/Al) ratio and zinc loading of 12%) shows the best performance among all the studied catalysts. 97.8%conversion of allyl alcohol and 37.9%selectivity toward 3-picoline are obtained on this catalyst using reaction conditions:atmospheric pressure, at 420℃, ammonia/allyl alcohol mole ratio 3:1 and gas hour space velocity 300 h-1. The characterization results, obtained by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and FT-IR of absorbed pyridine, indicate that zinc on Zn12/H-ZSM-5(80) is Zn2+, there is Lewis acid on HZSM-5. In 3-picoline formation, ZnO provides active sites of dehydrogenation reaction, and addition and cyclization reactions are mainly catalyzed by the Lewis acid.

  6. Iridium-Catalyzed Allylic Substitution (United States)

    Hartwig, John F.; Pouy, Mark J.

    Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

  7. An investigation of the Lewis acid mediated 1,3-dipolar cycloaddition between N-benzyl-C-(2-pyridyl)nitrone and allylic alcohol. Direct entry to isoxazolidinyl C-nucleosides. (United States)

    Merino, Pedro; Tejero, Tomas; Laguna, Mariano; Cerrada, Elena; Moreno, Ana; Lopez, Jose A


    The cycloaddition reaction of N-benzyl C-(2-pyridyl) nitrone with allylic alcohol has been carried out to obtain the corresponding 2-benzyl-3-(2-pyridyl)-5-hydroxymethylisoxazolidine. The influence of Lewis acids in the reaction has been studied and a complete 3,5-regioselectivity and cis diastereoselectivity was observed when the reaction was carried out with 1.0 equiv of AgOTf, [Ag(OClO3)(PPh2Me)] or Zn(OTf)2. Insight into the mechanism of the reaction has been obtained by isolating and characterizing (X-ray) the intermediate complexes. Also, a model based on both experimental and theoretical results is proposed.

  8. Tandem Reduction/Cyclization of O-Nitrophenyl Propargyl Alcohols-A Novel Synthesis of 2- & 2,4-Disubstituted Quinolines and Application to the Synthesis of Streptonigrin (United States)


    pathways: (1) cyclization by a distinctly different mechanism, propagated by the electonic nature of the pyridyl substituent, or (2) reductive...X-ray lab book No. 1575 Crystal ID DeShong/Sandelier MJS-I-85Y Empirical formula C7H6N2O6 Formula weight 214.14 Temperature...Soc. 2001, 123, 3239-3242. (22) Thayer, A. M. Chemical & Engineering News 2005, 83, 69-82. (23) Madrid, P. B.; Sherrill, J.; Liou, A

  9. Rationalizing Ring-Size Selectivity in Intramolecular Pd-Catalyzed Allylations of Resonance-Stabilized Carbanions

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Mader, Mary M.; Vitale, Maxime


    Computational methods were applied to the Pd-catalyzed intramolecular allylations of resonance-stabilized carbanions obtained from amide and ketone substrates, with the aim of rationalizing the endo- vs. exo-selectivity in the cyclizations. In addition, ester substrates were prepared and subjecte...


    NARCIS (Netherlands)

    Rispens, Minze T.; Zondervan, Charon; Feringa, Bernard


    Several chiral Cu(II)-complexes of cyclic amino acids catalyse the enantioselective allylic oxidation of cyclohexene to cyclohexenyl esters. Cyclohexenyl propionate was obtained in 86% yield with e.e.'s up to 61%.

  11. Phosphine-catalyzed [4 + 1] annulation between α,β-unsaturated imines and allylic carbonates: synthesis of 2-pyrrolines. (United States)

    Tian, Junjun; Zhou, Rong; Sun, Haiyun; Song, Haibin; He, Zhengjie


    In this report, a phosphine-catalyzed [4 + 1] annulation between α,β-unsaturated imines and allylic carbonates is described. This reaction represents the first realization of catalytic [4 + 1] cyclization of 1,3-azadienes with in situ formed phosphorus ylides, which provides highly efficient and diastereoselective synthesis of 2-pyrrolines.

  12. Allyl 4-hydroxyphenyl carbonate

    Directory of Open Access Journals (Sweden)

    Víctor Hugo Flores Ahuactzin


    Full Text Available The title molecule, C10H10O4, is a functionalized carbonate used in the synthetic route to organic glasses. The central CH fragment of the allyl group is disordered over two positions, with occupancies in a 0.758 (10:0.242 (10ratio. This disorder reflects the torsional flexibility of the oxygen–allyl group, although both disordered parts present the expected anticlinal conformation, with O—CH2—CH=CH2 torsion angles of −111 (2 and 119.1 (4°. The crystal structure is based on chains parallel to [010], formed by O...H—O hydrogen bonds involving hydroxyl and carbonyl groups as donors and acceptors, respectively. The molecular packing is further stabilized by two weak C—H...π contacts from the benzene ring of the asymmetric unit with two benzene rings of neighboring molecules.

  13. Nanoscaled copper metal-organic framework (MOF) based on carboxylate ligands as an efficient heterogeneous catalyst for aerobic epoxidation of olefins and oxidation of benzylic and allylic alcohols. (United States)

    Qi, Yue; Luan, Yi; Yu, Jie; Peng, Xiong; Wang, Ge


    Aerobic epoxidation of olefins at a mild reaction temperature has been carried out by using nanomorphology of [Cu3(BTC)2] (BTC = 1,3,5-benzenetricarboxylate) as a high-performance catalyst through a simple synthetic strategy. An aromatic carboxylate ligand was employed to furnish a heterogeneous copper catalyst and also serves as the ligand for enhanced catalytic activities in the catalytic reaction. The utilization of a copper metal-organic framework catalyst was further extended to the aerobic oxidation of aromatic alcohols. The shape and size selectivity of the catalyst in olefin epoxidation and alcohol oxidation was investigated. Furthermore, the as-synthesized copper catalyst can be easily recovered and reused several times without leaching of active species or significant loss of activity.

  14. γ‐ and δ-Lactams through Palladium-Catalyzed Intramolecular Allylic Alkylation: Enantioselective Synthesis, NMR Investigation, and DFT Rationalization

    DEFF Research Database (Denmark)

    Bantreil, Xavier; Prestat, Guillaume; Moreno, Aitor;


    the cyclization reactions to take place in up to 94:6 enantiomeric ratio. A model Pd-allyl complex has been prepared and studied through NMR spectroscopic analysis, which provided insight into the processes responsible for the observed enantiomeric ratios. DFT studies were used to characterize the diastereomeric...


    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhenfeng; HU Xingzhou; YAN Qing


    Photoinduced grafting of acrylic and allyl monomers on polyethylene surface was generally studied by using benzophenone (BP) as a photoinitiator. The grafting process was carried out either in vapor-phase or in solution of the monomers. In the vapor-phase reaction with a filter used to cut off the short wavelength UV light, allyl amine is the most reactive of the four monomers used and acrylic amide is comparatively more reactive than acrylic acid and allyl alcohol. Acetone, as a solvent and carrier for initiator and monomers, however, shows its reactivity to participate the reaction. The solution grafting with a filter is much faster than the corresponding vapor-phase reaction, and a fully covered surface by the grafted polymer can be achieved in this way.

  16. Catalyst-Free Imidation of Allyl Sulfides with Chloramine-T and Subsequent [2,3]-Sigmatropic Rearrangement

    Institute of Scientific and Technical Information of China (English)

    江玉波; 莫凡洋; 邱迪; 匡春香; 张艳; 王剑波


    A facile synthesis of various allyl sulfonamides based on imidation of allyl sulfides with chloramine-T and sub- sequent [2,3]-sigmatropic rearrangement has been achieved without metal catalysts. The reaction completes smoothly within 10 min, providing excellent yields in environment friendly solvent of alcohol. Functional groups such as bromine, hydroxyl, protected amido and aldehyde are tolerant under this condition.

  17. Scalable and sustainable electrochemical allylic C-H oxidation (United States)

    Horn, Evan J.; Rosen, Brandon R.; Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D.; Baran, Phil S.


    New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as “classics”. Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.

  18. The Lewis Acid-promoted Novel Cyclization Reactions Towards N-adn O-Containing Heterocycles

    Institute of Scientific and Technical Information of China (English)

    Shoko; Yamazaki


    1 Results Nitrogen and oxygen-containing heterocyclic systems are important structures in organic chemistry because of their presence in many biologically active compounds.In this work,a new zinc and indium-promoted conjugate addition-cyclization reaction to afford nitrogen and oxygen-containing five-membered heterocycles has been developed.A Lewis acid-catalyzed cyclization of an ethenetricarboxylate derivative with propargylamines or propargyl alcohols to give methylenepyrrolidines and methylenetetrah...

  19. Tsuji-Trost N-allylation with allylic acetates using cellulose-Pd catalyst (United States)

    Allylic amines are synthesized using heterogeneous cellulose-Pd catalyst via N-allylation of amines; aliphatic and benzyl amines undergo facile reaction with substituted and unsubstituted allyl acetates in high yields.

  20. [3,3]-sigmatropic rearrangements of fluorinated allyl (Thio)cyanates - a tool for the synthesis of fluorinated (Thio)ureas. (United States)

    Ramb, Daniel C; Kost, Lisa; Haufe, Günter


    The first (thio)cyanate to iso(thio)cyanate rearrangements based on 2-fluoroallylic alcohols are presented. Long-chain 2-fluoroallylic alcohols were converted to corresponding N-unsubstituted carbamates by treatment with trichloroacetyl isocyanate. Dehydration using trifluoroacetic anhydride in the presence of triethylamine formed intermediate allylic cyanates, which immediately underwent sigmatropic rearrangement to fluorinated allyl isocyanates. Without isolation the latter delivered fluorinated ureas by addition of amines. The thiocyanate to isothiocyanate rearrangements started from the same fluorinated allylic alcohols, which were first converted to mesylates. Heating in THF with potassium thiocyanate led to fluorinated allyl isothiocyanates, via [3,3]-sigmatropic rearrangement of intermediate allyl thiocyanates. The formed products were further reacted with amines to fluorinated thioureas.

  1. Chiral Phosphoric Acid Catalyzed Enantioselective Allylation of Aldehydes with Allyltrichlorosilane%Chiral Phosphoric Acid Catalyzed Enantioselective Allylation of Aldehydes with Allyltrichlorosilane

    Institute of Scientific and Technical Information of China (English)

    程柯; 范甜甜; 孙健


    Easily accessible chiral phosphoric acid lb has been applied as efficient organocatalyst for the asymmetric al- lylation of aldehydes with allyltrichlorosilane. In the presence of 20 mol% of lb, the allylation of a broad range of aldehydes proceeded smoothly to give the corresponding homoallylic alcohol with up to 87% ee and 97% yield.

  2. Alcohol (United States)

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  3. Alcohol (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  4. Green chemistry: solvent- and metal-free Prins cyclization. Application to sequential reactions. (United States)

    Clarisse, Damien; Pelotier, Béatrice; Piva, Olivier; Fache, Fabienne


    Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives.

  5. The allylic chalcogen effect in olefin metathesis

    Directory of Open Access Journals (Sweden)

    Yuya A. Lin


    Full Text Available Olefin metathesis has emerged as a powerful tool in organic synthesis. The activating effect of an allylic hydroxy group in metathesis has been known for more than 10 years, and many organic chemists have taken advantage of this positive influence for efficient synthesis of natural products. Recently, the discovery of the rate enhancement by allyl sulfides in aqueous cross-metathesis has allowed the first examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chemical biology. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic hydroxy groups, suggests that allyl chalcogens generally play an important role in modulating the rate of olefin metathesis. In this review, we discuss the effect of allylic chalcogens in olefin metathesis and highlight its most recent applications in synthetic chemistry and protein modifications.

  6. The allylic chalcogen effect in olefin metathesis (United States)

    Lin, Yuya A


    Summary Olefin metathesis has emerged as a powerful tool in organic synthesis. The activating effect of an allylic hydroxy group in metathesis has been known for more than 10 years, and many organic chemists have taken advantage of this positive influence for efficient synthesis of natural products. Recently, the discovery of the rate enhancement by allyl sulfides in aqueous cross-metathesis has allowed the first examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chemical biology. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic hydroxy groups, suggests that allyl chalcogens generally play an important role in modulating the rate of olefin metathesis. In this review, we discuss the effect of allylic chalcogens in olefin metathesis and highlight its most recent applications in synthetic chemistry and protein modifications. PMID:21283554

  7. Interplay of metal-allyl and metal-metal bonding in dimolybdenum allyl complexes

    Energy Technology Data Exchange (ETDEWEB)

    John, Kevin D [Los Alamos National Laboratory; Martin, Richard L [Los Alamos National Laboratory; Obrey, Steven J [Los Alamos National Laboratory; Scott, Brian L [Los Alamos National Laboratory


    Addition of PMe{sub 3} to Mo{sub 2}(allyl){sub 4} afforded Mo{sub 2}(allyl){sub 4}(PMe{sub 3}){sub 2}, in which two of the allyl groups adopt an unprecedented {mu}{sub 2{sup -}}{eta}{sup 1}, {eta}{sup 3} bonding mode; theoretical studies elucidate the role sof the {sigma}- and {pi}-donor ligands in the interplay of metal-allyl and metal-metal bonding.

  8. Process for the synthesis of unsaturated alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Maughon, Bob R.; Burdett, Kenneth A.; Lysenko, Zenon


    A process of preparing an unsaturated alcohol (olefin alcohol), such as, a homo-allylic mono-alcohol or homo-allylic polyol, involving protecting a hydroxy-substituted unsaturated fatty acid or fatty acid ester, such as methyl ricinoleate, derived from a seed oil, to form a hydroxy-protected unsaturated fatty acid or fatty acid ester; homo-metathesizing or cross-metathesizing the hydroxy-protected unsaturated fatty acid or fatty acid ester to produce a product mixture containing a hydroxy-protected unsaturated metathesis product; and deprotecting the hydroxy-protected unsaturated metathesis product under conditions sufficient to prepare the unsaturated alcohol. Preferably, methyl ricinoleate is converted by cross-metathesis or homo-metathesis into the homo-allylic mono-alcohol 1-decene-4-ol or the homo-allylic polyol 9-octadecene-7,12-diol, respectively.

  9. A Green Approach for Allylations of Aldehydes and Ketones: Combining Allylborate, Mechanochemistry and Lanthanide Catalyst

    Directory of Open Access Journals (Sweden)

    Viviane P. de Souza


    Full Text Available Secondary and tertiary alcohols synthesized via allylation of aldehydes and ketones are important compounds in bioactive natural products and industry, including pharmaceuticals. Development of a mechanochemical method using potassium allyltrifluoroborate salt and water, to successfully perform the allylation of aromatic and aliphatic carbonyl compounds is reported for the first time. By controlling the grinding parameters, the methodology can be selective, namely, very efficient for aldehydes and ineffective for ketones, but by employing lanthanide catalysts, the reactions with ketones can become practically quantitative. The catalyzed reactions can also be performed under mild aqueous stirring conditions. Considering the allylation agent and its by-products, aqueous media, energy efficiency and use of catalyst, the methodology meets most of the green chemistry principles.

  10. Alcohol

    NARCIS (Netherlands)

    Hendriks, H.F.; Tol, A. van


    Alcohol consumption affects overall mortality. Light to moderate alcohol consumption reduces the risk of coronary heart disease; epidemiological, physiological and genetic data show a causal relationship. Light to moderate drinking is also associated with a reduced risk of other vascular diseases an

  11. Highly enantio- and diastereoselective allylic alkylation of Morita-Baylis-Hillman carbonates with allyl ketones

    KAUST Repository

    Tong, Guanghu


    The asymmetric allylic alkylation of Morita-Baylis-Hillman (MBH) carbonates with allyl ketones has been developed. The α-regioselective alkylation adducts, containing a hexa-1,5-diene framework with important synthetic value, were achieved in up to 83% yield, >99% ee, and 50:1 dr by using a commercially available Cinchona alkaloid as the catalyst. From the allylic alkylation adduct, a cyclohexene bearing two adjacent chiral centers was readily prepared. © 2013 American Chemical Society.

  12. Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L. (United States)

    Luo, Dan; Callari, Roberta; Hamberger, Britta; Wubshet, Sileshi Gizachew; Nielsen, Morten T.; Andersen-Ranberg, Johan; Hallström, Björn M.; Cozzi, Federico; Lindberg Møller, Birger; Hamberger, Björn


    The seed oil of Euphorbia lathyris L. contains a series of macrocyclic diterpenoids known as Euphorbia factors. They are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis, a precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating the origin of the intramolecular carbon–carbon bonds present in lathyrane and ingenane diterpenoids. This unconventional cyclization describes the ring closure of the macrocyclic diterpene casbene. Through transcriptomic analysis of E. lathyris L. mature seeds and in planta functional characterization, we identified three enzymes involved in the cyclization route from casbene to jolkinol C, a lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71 clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio-specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation of the hydroxyl groups, leading to the subsequent rearrangement and cyclization. The discovery of this nonconventional cyclization may provide the key link to complete elucidation of the biosynthetic pathways of ingenol mebutate and other bioactive macrocyclic diterpenoids. PMID:27506796

  13. Alcohol (United States)

    ... changes that come from drinking alcohol can make people do stupid or embarrassing things, like throwing up or peeing on themselves. Drinking also gives people bad breath, and no one enjoys a hangover. ...

  14. Lewis base catalyzed enantioselective allylic hydroxylation of Morita-Baylis-Hillman carbonates with water

    KAUST Repository

    Zhu, Bo


    A Lewis base catalyzed allylic hydroxylation of Morita-Baylis-Hillman (MBH) carbonates has been developed. Various chiral MBH alcohols can be synthesized in high yields (up to 99%) and excellent enantioselectivities (up to 94% ee). This is the first report using water as a nucleophile in asymmetric organocatalysis. The nucleophilic role of water has been verified using 18O-labeling experiments. © 2011 American Chemical Society.

  15. Ruthenium Hydride/Brønsted Acid-Catalyzed Tandem Isomerization/N-Acyliminium Cyclization Sequence for the Synthesis of Tetrahydro-β-carbolines

    DEFF Research Database (Denmark)

    Hansen, Casper Lykke; Clausen, Janie Regitse Waël; Ohm, Ragnhild Gaard;


    This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Brønsted acid- catalyzed isomerization of allylic amides to N-acyliminium ion intermediates which are trapped by a tethered indolenucleophile. The methodol...... the Suzuki cross-coupling reaction to the isomerization/N-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively...

  16. Synthesis of allyl esters of fatty acids and their ovicidal effect on Cydia pomonella (L.). (United States)

    Escribà, Marc; Barbut, Montserrat; Eras, Jordi; Canela, Ramon; Avilla, Jesús; Balcells, Mercè


    Eight allyl esters of fatty acids were synthesized in moderate to high yields with a novel two-step procedure using glycerol as a starting material. The two-step methodology avoids the use of allyl alcohol. The first step consisted of heating at 80 degrees C for 48 h a 2:1:5 mmol mixture of glycerol, a fatty acid, and chlorotrimethylsilane in a solvent-free medium. The crude compound was then dissolved in butanone and heated at 115 degrees C in the presence of NaI. A tandem Finkelstein rearrangement-elimination reaction occurs, producing the corresponding allyl ester. The activity of these esters against Cydia pomonella (L.) (Lepidoptera: Tortricidae) eggs was tested in the laboratory by topical application of one 0.1 microL drop. All of the compounds showed a concentration-mortality response and caused 100% mortality at the highest concentration tested (10 mg/mL). There was an inverse relationship between the alkyl chain length and the ovicidal activity of the allyl ester; the LC(50) and the LC(90) of the two compounds that have the longer alkyl chains were significantly higher than those of the rest of the compounds. The ovicidal and IGR activities of this kind of compound appear to be unprecedented.

  17. [N-allyl-Dmt1]-endomorphins are micro-opioid receptor antagonists lacking inverse agonist properties. (United States)

    Marczak, Ewa D; Jinsmaa, Yunden; Li, Tingyou; Bryant, Sharon D; Tsuda, Yuko; Okada, Yoshio; Lazarus, Lawrence H


    [N-allyl-Dmt1]-endomorphin-1 and -2 ([N-allyl-Dmt1]-EM-1 and -2) are new selective micro-opioid receptor antagonists obtained by N-alkylation with an allyl group on the amino terminus of 2',6'-dimethyl-L-tyrosine (Dmt) derivatives. To further characterize properties of these compounds, their intrinsic activities were assessed by functional guanosine 5'-O-(3-[35S]thiotriphosphate) binding assays and forskolin-stimulated cyclic AMP accumulation in cell membranes obtained from vehicle, morphine, and ethanol-treated SK-N-SH cells and brain membranes isolated from naive and morphine-dependent mice; their mode of action was compared with naloxone or naltrexone, which both are standard nonspecific opioid-receptor antagonists. [N-allyl-Dmt1]-EM-1 and -2 were neutral antagonists under all of the experimental conditions examined, in contrast to naloxone and naltrexone, which behave as neutral antagonists only in membranes from vehicle-treated cells and mice but act as inverse agonists in membranes from morphine- and ethanol-treated cells as well as morphine-treated mice. Both endomorphin analogs inhibited the naloxone- and naltrexone-elicited withdrawal syndromes from acute morphine dependence in mice. This suggests their potential therapeutic application in the treatment of drug addiction and alcohol abuse without the adverse effects observed with inverse agonist alkaloid-derived compounds that produce severe withdrawal symptoms.

  18. Rh-Catalyzed Chemo- and Enantioselective Hydrogenation of Allylic Hydrazones. (United States)

    Hu, Qiupeng; Hu, Yanhua; Liu, Yang; Zhang, Zhenfeng; Liu, Yangang; Zhang, Wanbin


    A highly efficient P-stereogenic diphosphine-rhodium complex was applied to the chemo- and enantioselective hydrogenation of allylic hydrazones for the synthesis of chiral allylic hydrazines in 89-96 % yields and with 82-99 % ee values. This methodology was successfully applied to the preparation of versatile chiral allylic amine derivatives.

  19. Elementary reaction allyl radical with oxygen

    Institute of Scientific and Technical Information of China (English)

    DONG Feng; KONG Fanao


    The elementary reaction between allyl radical with oxygen molecule wasexperimentally investigated. The allyl radical was produced via laser photolysis of C3H5Br in gaseous phase. Nascent vibrational excited products HCO, CO2, CH3CHO and HCOOH were recorded by the time- resolved Fourier transform infrared spectroscopy. The product channels of C2H5+CO2, CH3CHO+HCO, and HCOOH + C2H3 have been identified. The vibrational populations of product CO2 are obtained by spectral simulation. A mechanism forming a series of three-membered ring-struc- ture intermediates is suggested.

  20. Study on the Preparation of Allyl-modified Starch in Isopropyl/Water Medium for Warp Sizing

    Institute of Scientific and Technical Information of China (English)

    LI Man-li; ZHU Zhi-feng; ZHANG Long-qiu


    A new method for the pretreatment of starch by etherification was developed to eliminate the problems of lower grafting efficiency associated with the preparation of starch graft copolymers as warp sizing agents.The etherification of starch with allyl chloride was investigated in order to effectively enhance the reaction efficiency.The technological variables of the reaction considered for evaluating the etherification included sodium hydroxide amount,water content in water-isopropyi alcohol medium,allyl cldoride concentration,reaction temperature and reaction time.The experimental result demonstrated that the variables considered showed evident effect on the reaction efficiency.For the etherification,a condition of 20% for the water content,1.5:1 for the molar ratio of sodium hydroxide to allyl chloride.and at 30℃ under 24h reaction is Sufficient to retain the reaction efficiency above 50%.Furthermore,a contrast test demonstrated that the graft efficiency can be increased with the etherification pretreatment.

  1. Palladacyclic imidazoline-naphthalene complexes: synthesis and catalytic performance in Pd(II)-catalyzed enantioselective reactions of allylic trichloroacetimidates. (United States)

    Cannon, Jeffrey S; Frederich, James H; Overman, Larry E


    A new family of air- and moisture-stable enantiopure C,N-palladacycles (PIN-acac complexes) were prepared in good overall yield in three steps from 2-iodo-1-naphthoic acid and enantiopure β-amino alcohols. Three of these PIN complexes were characterized by single-crystal X-ray analysis. As anticipated, the naphthalene and imidazoline rings of PIN-acac complexes 18a and 18b were canted significantly from planarity and projected the imidazoline substituents R(1) and R(2) on opposite faces of the palladium square plane. Fifteen PIN complexes were evaluated as catalysts for the rearrangement of prochiral (E)-allylic trichloroacetimidate 19 (eq 2) and the S(N)2' allylic substitution of acetic acid with prochiral (Z)-allylic trichloroacetimidate 23. Although these complexes were kinetically poor catalysts for the Overman rearrangement, they were good catalysts for the allylic substitution reaction, providing branched allylic esters in high yield. However, enantioselectivities were low to moderate and significantly less than that realized with palladacyclic complexes of the COP family. Computational studies support an anti-acetoxypalladation/syn-deoxypalladation mechanism analogous to that observed with COP catalysts. The computational study further suggests that optimizing steric influence in the vicinity of the carbon ligand of a chiral C,N-palladacycle, rather than near the nitrogen heterocycle, is the direction to pursue in future development of improved enantioselective catalysts of this motif.

  2. Knottin cyclization: impact on structure and dynamics

    Directory of Open Access Journals (Sweden)

    Gracy Jérôme


    Full Text Available Abstract Background Present in various species, the knottins (also referred to as inhibitor cystine knots constitute a group of extremely stable miniproteins with a plethora of biological activities. Owing to their small size and their high stability, knottins are considered as excellent leads or scaffolds in drug design. Two knottin families contain macrocyclic compounds, namely the cyclotides and the squash inhibitors. The cyclotide family nearly exclusively contains head-to-tail cyclized members. On the other hand, the squash family predominantly contains linear members. Head-to-tail cyclization is intuitively expected to improve bioactivities by increasing stability and lowering flexibility as well as sensitivity to proteolytic attack. Results In this paper, we report data on solution structure, thermal stability, and flexibility as inferred from NMR experiments and molecular dynamics simulations of a linear squash inhibitor EETI-II, a circular squash inhibitor MCoTI-II, and a linear analog lin-MCoTI. Strikingly, the head-to-tail linker in cyclic MCoTI-II is by far the most flexible region of all three compounds. Moreover, we show that cyclic and linear squash inhibitors do not display large differences in structure or flexibility in standard conditions, raising the question as to why few squash inhibitors have evolved into cyclic compounds. The simulations revealed however that the cyclization increases resistance to high temperatures by limiting structure unfolding. Conclusion In this work, we show that, in contrast to what could have been intuitively expected, cyclization of squash inhibitors does not provide clear stability or flexibility modification. Overall, our results suggest that, for squash inhibitors in standard conditions, the circularization impact might come from incorporation of an additional loop sequence, that can contribute to the miniprotein specificity and affinity, rather than from an increase in conformational rigidity

  3. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives. (United States)

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E


    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products.

  4. Pressure Dependent Product Formation in the Photochemically Initiated Allyl + Allyl Reaction

    Directory of Open Access Journals (Sweden)

    Thomas Zeuch


    Full Text Available Photochemically driven reactions involving unsaturated radicals produce a thick global layer of organic haze on Titan, Saturn’s largest moon. The allyl radical self-reaction is an example for this type of chemistry and was examined at room temperature from an experimental and kinetic modelling perspective. The experiments were performed in a static reactor with a volume of 5 L under wall free conditions. The allyl radicals were produced from laser flash photolysis of three different precursors allyl bromide (C3H5Br, allyl chloride (C3H5Cl, and 1,5-hexadiene (CH2CH(CH22CHCH2 at 193 nm. Stable products were identified by their characteristic vibrational modes and quantified using FTIR spectroscopy. In addition to the (re- combination pathway C3H5+C3H5 → C6H10 we found at low pressures around 1 mbar the highest final product yields for allene and propene for the precursor C3H5Br. A kinetic analysis indicates that the end product formation is influenced by specific reaction kinetics of photochemically activated allyl radicals. Above 10 mbar the (re- combination pathway becomes dominant. These findings exemplify the specificities of reaction kinetics involving chemically activated species, which for certain conditions cannot be simply deduced from combustion kinetics or atmospheric chemistry on Earth.


    Directory of Open Access Journals (Sweden)

    Gagik Torosyan


    Full Text Available It has been established the possibility for phenol allylation on natural zeolites and them analogs. Here is demonstrated the synthesis of allyl phenol, which has wide industrial applications. The offered method in comparison with the traditional methods has more advantages – higher selectivity, smaller material and power resources consumption. It has been obtained the mixture of allylating phenols (30% in general with allyl phenyl ether (1 with 80% yields. At 600 K is obtained allylphenyl ether, at 700 K beginning the formation of allyl phenols, which is the result of direct C-allylation of the aromatic ring. It has been investigated the possibility of Claisen rearrangement in the same conditions. All of that are established by gas-liquid chromatography and liquid chromatography data.

  6. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (-)-linalyl pyrophosphate to (+)- and (-)-pinene and (+)- and (-)-camphene

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.; Satterwhite, D.M.; Cane, D.E.; Chang, C.C.


    Cyclase I from Salvia officinalis leaf catalyzes the conversion of geranyl pyrophosphate to the stereo-chemically related bicyclic monoterpenes (+)-alpha-pinene and (+)-camphene and to lesser quantities of monocyclic and acyclic olefins, whereas cyclase II from this plant tissue converts the same acyclic precursor to (-)-alpha-pinene, (-)-beta-pinene and (-)-camphene as well as to lesser amounts of monocyclics and acyclics. These antipodal cyclizations are considered to proceed by the initial isomerization of the substrate to the respective bound tertiary allylic intermediates (-)-(3R)- and (+)-(3S)-linalyl pyrophosphate. ((3R)-8,9-14C,(3RS)-1E-3H)Linalyl pyrophosphate (3H:14C = 5.14) was tested as a substrate with both cyclases to determine the configuration of the cyclizing intermediate. This substrate with cyclase I yielded alpha-pinene and camphene with 3H:14C ratios of 3.1 and 4.2, respectively, indicating preferential, but not exclusive, utilization of the (3R)-enantiomer. With cyclase II, the doubly labeled substrate gave bicyclic olefins with 3H:14C ratios of from 13 to 20, indicating preferential, but not exclusive, utilization of the (3S)-enantiomer in this case. (3R)- and (3S)-(1Z-3H)linalyl pyrophosphate were separately compared to the achiral precursors (1-3H)geranyl pyrophosphate and (1-3H)neryl pyrophosphate (cis-isomer) as substrates for the cyclizations. With cyclase I, geranyl, neryl, and (3R)-linalyl pyrophosphate gave rise exclusively to (+)-alpha-pinene and (+)-camphene, whereas (3S)-linayl pyrophosphate produced, at relatively low rates, the (-)-isomers. With cyclase II, geranyl, neryl, and (3S)-linalyl pyrophosphate yielded exclusively the (-)-isomer series, whereas (3R)-linalyl pyrophosphate afforded the (+)-isomers at low rates.

  7. Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX(5-)[3,3] Rearrangement. (United States)

    Fleming, Fraser F; Ravikumar, P C; Yao, Lihua


    Sequential addition of vinylmagnesium bromide and NbCl(5), or NbBr(5), to a series of aldehydes and ketones directly provides homologated, allylic halides. Transposition of the intermediate vinyl alkoxide is envisaged through a metalla-halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal carbon. The [3,3] rearrangement is equally effective for the conversion of a propargyllic alcohol to the corresponding allenyl bromide.

  8. Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX5-[3,3] Rearrangement (United States)

    Fleming, Fraser F.; Ravikumar, P. C.; Yao, Lihua


    Sequential addition of vinylmagnesium bromide and NbCl5, or NbBr5, to a series of aldehydes and ketones directly provides homologated, allylic halides. Transposition of the intermediate vinyl alkoxide is envisaged through a metalla-halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal carbon. The [3,3] rearrangement is equally effective for the conversion of a propargyllic alcohol to the corresponding allenyl bromide. PMID:20046989

  9. Nano-Aluminum Powder Mediated Allylation of Carbonyl Compounds in Aqueous Media

    Institute of Scientific and Technical Information of China (English)

    YUAN Shi-Zhen; LIU Jin


    A new and effective Barbier-Grignard allylation of aldehydes or ketones has been carried out with nano-aluminum powder in aqueous 0.1 mol·L-1 NH4Cl (aq.) under an atmosphere of nitrogen. Aromatic carbonyl compounds gave homoallylic alcohols in good yields. The effectiveness of reaction was strongly influenced by the steric environment surrounding the carbonyl group. Aliphatic carbonyl compounds proceeded in low yields. The dominant stereoisomer was an erythro-isomer when an ortho-hydroxyl carbonyl compound was reacted under such a reaction condition.

  10. Side Chain Cyclized Aromatic Amino Acids

    DEFF Research Database (Denmark)

    Van der Poorten, Olivier; Knuhtsen, Astrid; Sejer Pedersen, Daniel


    Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute...... the peptide pharmacophore is equally important. Control of χ-space utilizes conformationally constrained amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected...... to the peptide backbone to provide control of χ(1)- and χ(2)-space. The manifold applications for cyclized analogues of the aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry are showcased herein with examples of enzyme inhibitors and ligands for G protein-coupled receptors....

  11. Green synthesis of allyl isobornyl ether%烯丙基异冰片基醚绿色合成研究

    Institute of Scientific and Technical Information of China (English)

    王士康; 徐徐; 兰蓝; 樊媛媛; 王石发


    以莰烯和烯丙醇为原料,研究了烯丙基异冰片基醚的绿色合成工艺,探讨了催化剂种类及用量、反应温度、反应时间,以及烯丙醇与莰烯物质的量之比对莰烯醚化反应选择性及烯丙基异冰片基醚产物得率的影响.采用正交试验方法确定了烯丙基异冰片基醚的最适工艺条件:A-15型阳离子树脂为催化剂,催化剂用量为烯丙醇和莰烯原料总质量的5%,烯丙醇与莰烯物质的量之比为1.5:1,反应温度75℃,反应时间7h.在此条件下工业莰烯转化率为85.5%,反应选择性为97.5%,烯丙基异冰片基醚得率为83.4%.最后采用GC-MS、IR等分析技术对合成所得产物的结构进行了分析测定.%Green synthetic method of allyl isobornyl ether was investigated by using camphene and allyl alcohol as the raw materials in this paper. Influence of catalysts and their usages, reaction temperature, reaction time, and the molar ratio of allyl alcohol to camphene on the selectivity of etherification and the yield of allyl isobornyl ether were examined, and the optimum synthesis conditions were determined based on the orthogonal test results as follows: A-15 resin was used as the catalyst for etherification, and the amount of A-15 cationic exchange resin was 5 % (based on the total weight of camphene and allyl alcohol) ; molar ratio of allyl alcohol to camphene was 1. 5-1; reaction temperature and reaction time were 75 ℃ and 7 h, respectively. The conversion ratio of camphene and the reaction selectivity reached 85. 5 % and 97. 5 % respectively, and the yield of allyl isobornyl ether also reached 83. 4 %. The structure of allyl isobornyl ether was identified by GC-MS and IR spectra.

  12. Use of Cyclic Allylic Bromides in the Zinc–Mediated Aqueous Barbier–Grignard Reaction

    Directory of Open Access Journals (Sweden)

    Suzanne M. Perala


    Full Text Available The zinc–mediated aqueous Barbier–Grignard reaction of cyclic allylic bromide substrates with various aldehydes and ketones to afford homoallylic alcohols was investigated. Aromatic aldehydes and ketones afforded adducts in good yields (66–90% and with good diastereoselectivities. Non–aromatic aldehydes also reacted well under these conditions, but only poor yields were obtained with non–aromatic ketones. Regioselectivity was high when some substituted cyclic allylic bromides were investigated.

  13. Allyl borates: a novel class of polyhomologation initiators

    KAUST Repository

    Wang, De


    Allyl borates, a new class of monofunctional polyhomologation initiators, are reported. These monofunctional initiators are less sensitive and more effective towards polymethylene-based architectures. As an example, the synthesis of α-vinyl-ω-hydroxypolymethylenes is given. By designing/synthesizing different allylic borate initiators, and using 1H and 11B NMR spectroscopy, the initiation mechanism was elucidated.

  14. Radiation and thermal polymerization of allyl(p-allylcarbonate) benzoate

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-V, D., E-mail: dlopez@siu.buap.m [Facultad de Ciencias Quimicas, Benemerita Universidad Autonoma de Puebla, Antiguo Edificio de la Fac. de Cs., Quimica. Av. San Claudio y Boulevard de la 14 sur, Col. San Manuel, Puebla, Pue., CP 72500 (Mexico); Herrera-G, A.M., E-mail: mherrera@uaeh.reduaeh.m [Centro de Inv. en Materiales y Metalurgia, UAEH. Km 4.5, C.U., CP 42184, Pachuca de S. Hidalgo (Mexico); Castillo-Rojas, S., E-mail: castillo@nucleares.unam.m [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, 04510 DF (Mexico)


    Bulk polymerization of novel allyl(p-allylcarbonate) benzoate was investigated using different sources of energy, such as gamma rays, ultraviolet rays as well as thermal polymerization. The poly(allyl(p-allylcarbonate) benzoate) obtained is a cross-linking, transparent, thermoset polycarbonate. Compositions of the monomer and the polycarbonate were analyzed by infrared spectroscopy, elemental analysis, and {sup 1}H NMR spectroscopy.

  15. Structural determinants of reductive terpene cyclization in iridoid biosynthesis

    DEFF Research Database (Denmark)

    Kries, Hajo; Caputi, Lorenzo; Stevenson, Clare E M;


    The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a ...... to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are highlighted....

  16. Direct aerobic oxidation of primary alcohols to methyl esters catalyzed by a heterogeneous gold catalyst

    DEFF Research Database (Denmark)

    Nielsen, Inger Staunstrup; Taarning, Esben; Egeblad, Kresten


    Methyl esters can be produced in high yield by oxidising methanolic solutions of primary alcohols with dioxygen over a heterogeneous gold catalyst. The versatility of this new methodology is demonstrated by the fact that alkylic, benzylic and allylic alcohols, as well as alcohols containing...

  17. Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

    Directory of Open Access Journals (Sweden)

    Christine Basmadjian


    Full Text Available The dehydration and subsequent cyclization reactions of 1-styrylpropargyl alcohols was examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold.

  18. Novel carbocationic rearrangements of 1-styrylpropargyl alcohols. (United States)

    Basmadjian, Christine; Zhang, Fan; Désaubry, Laurent


    The dehydration and subsequent cyclization reactions of 1-styrylpropargyl alcohols was examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold.

  19. Novel carbocationic rearrangements of 1-styrylpropargyl alcohols


    Christine Basmadjian; Fan Zhang; Laurent Désaubry


    The dehydration and subsequent cyclization reactions of 1-styrylpropargyl alcohols was examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold.

  20. Novel carbocationic rearrangements of 1-styrylpropargyl alcohols (United States)

    Basmadjian, Christine; Zhang, Fan


    Summary The dehydration and subsequent cyclization reactions of 1-styrylpropargyl alcohols was examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold. PMID:26199656

  1. Alcoholism and Alcohol Abuse (United States)

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  2. Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Courtney; Pluth, Michael; Bergman, Robert; Raymond, Kenneth


    A primary goal in the design and synthesis of molecular hosts has been the selective recognition and binding of a variety of guests using non-covalent interactions. Supramolecular catalysis, which is the application of such hosts towards catalysis, has much in common with many enzymatic reactions, chiefly the use of both spatially appropriate binding pockets and precisely oriented functional groups to recognize and activate specific substrate molecules. Although there are now many examples which demonstrate how selective encapsulation in a host cavity can enhance the reactivity of a bound guest, all have failed to reach the degree of increased reactivity typical of enzymes. We now report the catalysis of the Nazarov cyclization by a self-assembled coordination cage, a carbon-carbon bond-forming reaction which proceeds under mild, aqueous conditions. The acceleration in this system is over a million-fold, and represents the first example of supramolecular catalysis that achieves the level of rate enhancement comparable to that observed in several enzymes. We explain the unprecedented degree of rate increase as due to the combination of (a) preorganization of the encapsulated substrate molecule, (b) stabilization of the transition state of the cyclization by constrictive binding, and (c) increase in the basicity of the complexed alcohol functionality.

  3. Zinc Mediated Tandem Fragmentation-Allylation of Methyl 5-Iodopentofuranosides

    DEFF Research Database (Denmark)

    Hyldtoft, Lene; Madsen, Robert


    In the presence of zinc and allyl bromide methyl 5-iodopentofuranosides undergo a tandem fragmentation alkylation to give functionalized dienes. These can undergo ring-closing olefin metathesis to produce cyclohexenes which on dihydroxylation give quercitols....

  4. Chiral allylic and allenic metal reagents for organic synthesis. (United States)

    Marshall, James A


    This account traces the evolution of our work on the synthesis of chiral allylic and allenic organometal compounds of tin, silicon, zinc, and indium and their application to natural product synthesis over the past quarter century.

  5. Copper-catalyzed regioselective allylic substitution reactions with indium organometallics. (United States)

    Rodríguez, David; Sestelo, José Pérez; Sarandeses, Luis A


    The first nucleophilic allylic substitution reactions of triorganoindium compounds with allylic halides and phosphates are reported. The reactions of trialkyl- and triarylindium reagents with cinnamyl and geranyl halides and phosphates, with the aid of copper catalysis [Cu(OTf)(2)/P(OEt)(3)], are described. In general, the reaction proceeds efficiently to give good yields and regioselectively to afford the S(N)2' product.

  6. Molecular Mechanics and Quantum Chemistry Based Study of Nickel-N-Allyl Urea and N-Allyl Thiourea Complexes

    Directory of Open Access Journals (Sweden)

    P. D. Sharma


    Full Text Available Eigenvalue, eigenvector and overlap matrix of nickel halide complex of N-allyl urea and N-allyl thiourea have been evaluated. Our results indicate that ligand field parameters (Dq, B’ and β evaluated earlier by electronic spectra are very close to values evaluated with the help of eigenvalues and eigenvectors. Eigenvector analysis and population analysis shows that in bonding 4s, 4p, and 3dx2-y2, 3dyz orbitals of nickel are involved but the coefficient values differ in different complexes. Out of 4px, 4py, 4pz the involvement of either 4pz or 4py, is noticeable. The theoretically evaluated positions of infrared bands indicate that N-allyl urea is coordinated to nickel through its oxygen and N-allyl thiourea is coordinated to nickel through its sulphur which is in conformity with the experimental results.

  7. BF3 x Et2O-mediated cascade cyclizations: synthesis of schweinfurthins F and G. (United States)

    Mente, Nolan R; Neighbors, Jeffrey D; Wiemer, David F


    The total synthesis of the natural stilbene (+)-schweinfurthin G (8) has been accomplished through a sequence based on an efficient cationic cascade cyclization. This cascade process is initiated by Lewis acid promoted ring opening of an epoxide and terminated through a novel reaction with a phenolic oxygen "protected" as its MOM ether. Several Lewis acids have been examined for their ability to induce this new reaction, and BF3 x Et2O was found to be the most effective. The only major byproduct under these conditions was one where the expected secondary alcohol was found as its MOM ether derivative (e.g., 30). While this byproduct could be converted to the original target compound through hydrolysis, it also could be employed as a protected alcohol to allow preparation of a benzylic phosphonate (43) without dehydration of the secondary alcohol. The resulting phosphonate was employed in a Horner-Wadsworth-Emmons condensation with an aldehyde representing the right half of the target compounds, an approach complementary to previous studies based on condensation of a right-half phosphonate and a left-half aldehyde.

  8. Catalytic enantioselective cyclization and C3-fluorination of polyenes. (United States)

    Cochrane, Nikki A; Nguyen, Ha; Gagne, Michel R


    (Xylyl-phanephos)Pt(2+) in combination with XeF(2) mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates. Isolated yields were typically in the 60-69% range while enantioselectivities reached as high as 87%. The data are consistent with a stereoretentive fluorination of a P(2)Pt-alkyl cation intermediate.

  9. Polyphosphorous acid catalyzed cyclization in the synthesis of cryptolepine derivatives

    Institute of Scientific and Technical Information of China (English)


    11-Oxo-10,11-dihydroxy-5H-indolo[3,2,b]quinoline7-carboxylic acid was obtained specifically by polyphosphorous acid catalyzed cyclization with optimal reaction conditions. Biological assays showed that it potentially inhibits the proteasomal chymotrypsin-like activity in vitro and suppresses breast cancer cell growth.

  10. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. (United States)

    Crawford, Jason M; Korman, Tyler P; Labonte, Jason W; Vagstad, Anna L; Hill, Eric A; Kamari-Bidkorpeh, Oliver; Tsai, Shiou-Chuan; Townsend, Craig A


    Polyketides are a class of natural products with diverse structures and biological activities. The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs) results from regiospecific cyclizations of reactive poly-beta-keto intermediates. How poly-beta-keto species are synthesized and stabilized, how their chain lengths are determined, and, in particular, how specific cyclization patterns are controlled have been largely inaccessible and functionally unknown until recently. A product template (PT) domain is responsible for controlling specific aldol cyclization and aromatization of these mature polyketide precursors, but the mechanistic basis is unknown. Here we present the 1.8 A crystal structure and mutational studies of a dissected PT monodomain from PksA, the NR-PKS that initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B(1) in Aspergillus parasiticus. Despite having minimal sequence similarity to known enzymes, the structure displays a distinct 'double hot dog' (DHD) fold. Co-crystal structures with palmitate or a bicyclic substrate mimic illustrate that PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies reveal residues important for substrate binding and catalysis, and identify a phosphopantetheine localization channel and a deep two-part interior binding pocket and reaction chamber. Sequence similarity and extensive conservation of active site residues in PT domains suggest that the mechanistic insights gleaned from these studies will prove general for this class of IPKSs, and lay a foundation for defining the molecular rules controlling NR-PKS cyclization specificity.

  11. SnCl2/Cu-Mediated Carbonyl Allylation Reaction in Water:Scope,Selectivity and Mechanism

    Institute of Scientific and Technical Information of China (English)

    TAN,Xiang-Hui(谭翔晖); HOU,Yong-Quan(侯永泉); LIU,Lei(刘磊); GUO,Qing-Xiang(郭庆祥)


    Copper was found to be able to promote the SnC12-mediated carbonyl allylation reactions in water,giving the corresponding homoallylic alcohol products in very high yields.Detailed studies showed that the reaction could be applied to a variety of carbonyl compounds including those with hydroxyl,amino and nitro groups.It was also found that this reaction showed good regioselectivities for some substrates.Furthermore,carefully controled experiments and in situ NMR measurements provided important insights into the mechanism of the newly developed reaction.

  12. Structurally defined allyl compounds of main group metals: coordination and reactivity. (United States)

    Lichtenberg, Crispin; Okuda, Jun


    Organometallic allyl compounds are important as allylation reagents in organic synthesis, as polymerization catalysts, and as volatile metal precursors in material science. Whereas the allyl chemistry of synthetically relevant transition metals such as palladium and of the lanthanoids is well-established, that of main group metals has been lagging behind. Recent progress on allyl complexes of Groups 1, 2, and 12-16 now provides a more complete picture. This is based on a fundamental understanding of metal-allyl bonding interactions in solution and in the solid state. Furthermore, reactivity trends have been rationalized and new types of allyl-specific reactivity patterns have been uncovered. Key features include 1) the exploitation of the different types of metal-allyl bonding (highly ionic to predominantly covalent), 2) the use of synergistic effects in heterobimetallic compounds, and 3) the adjustment of Lewis acidity by variation of the charge of allyl compounds.

  13. Catalytic Enantioselective Allylic Amination of Olefins for the Synthesis of ent-Sitagliptin. (United States)

    Bao, Hongli; Bayeh, Liela; Tambar, Uttam K


    The presence of nitrogen atoms in most chiral pharmaceutical drugs has motivated the development of numerous strategies for the synthesis of enantioenriched amines. Current methods are based on the multi-step transformation of pre-functionalized allylic electrophiles into chiral allylic amines. The enantioselective allylic amination of unactivated olefins represents a more direct and attractive strategy. We report the enantioselective synthesis of ent-sitagliptin via an allylic amination of an unactivated terminal olefin.

  14. Redox-Neutral Rh(III)-Catalyzed Olefination of Carboxamides with Trifluoromethyl Allylic Carbonate. (United States)

    Park, Jihye; Han, Sangil; Jeon, Mijin; Mishra, Neeraj Kumar; Lee, Seok-Yong; Lee, Jong Suk; Kwak, Jong Hwan; Um, Sung Hee; Kim, In Su


    The rhodium(III)-catalyzed olefination of various carboxamides with α-CF3-substituted allylic carbonate is described. This reaction provides direct access to linear CF3-allyl frameworks with complete trans-selectivity. In particular, a rhodium catalyst provided Heck-type γ-CF3-allylation products via the β-O-elimination of rhodacycle intermediate and subsequent olefin migration process.

  15. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide. (United States)


    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  16. Tribromoisocyanuric acid/triphenylphosphine: a new system for conversion of alcohols into alkyl bromides

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Vitor S.C. de; Mattos, Marcio C.S. de, E-mail: [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Quimica. Departamento de Quimica Organica


    An efficient and facile method has been developed for the conversion of alcohols into alkyl bromides under neutral conditions using tribromoisocyanuric acid and triphenylphosphine (molar ratio 1.0:0.7:2.0, alcohol/tribromoisocyanuric acid/triphenylphosphine) in dichloromethane at room temperature. This method can be applied for the conversion of primary, secondary, benzilic and allylic alcohols, and their corresponding bromides are obtained in 67-82 % yield. Tertiary alcohols do not react under these conditions. (author)

  17. Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene (United States)

    Seidl, Frederick J


    Summary The scope of a recently reported method for the catalytic enantioselective bromochlorination of allylic alcohols is expanded to include a specific homoallylic alcohol. Critical factors for optimization of this reaction are highlighted. The utility of the product bromochloride is demonstrated by the first total synthesis of an antibacterial polyhalogenated monoterpene, (−)-anverene. PMID:27559385

  18. Sulfonium-based Ionic Liquids Incorporating the Allyl Functionality

    Directory of Open Access Journals (Sweden)

    Paul J. Dyson


    Full Text Available A series of sulfonium halides bearing allyl groups have been prepared andcharacterized. Anion metathesis with Li[Tf2N] and Ag[N(CN2] resulted in sulfonium-basedionic liquids which exhibit low viscosities at room temperature. The solid state structure ofone of the halide salts was determined by single crystal X-ray diffraction.

  19. Single pulse shock tube study of allyl radical recombination. (United States)

    Fridlyand, Aleksandr; Lynch, Patrick T; Tranter, Robert S; Brezinsky, Kenneth


    The recombination and disproportionation of allyl radicals has been studied in a single pulse shock tube with gas chromatographic measurements at 1-10 bar, 650-1300 K, and 1.4-2 ms reaction times. 1,5-Hexadiene and allyl iodide were used as precursors. Simulation of the results using derived rate expressions from a complementary diaphragmless shock tube/laser schlieren densitometry study provided excellent agreement with precursor consumption and formation of all major stable intermediates. No significant pressure dependence was observed at the present conditions. It was found that under the conditions of these experiments, reactions of allyl radicals in the cooling wave had to be accounted for to accurately simulate the experimental results, and this unusual situation is discussed. In the allyl iodide experiments, higher amounts of allene, propene, and benzene were found at lower temperatures than expected. Possible mechanisms are discussed and suggest that iodine containing species are responsible for the low temperature formation of allene, propene, and benzene.

  20. Electrochemical Allylic Oxidation of Olefins: Sustainable and Safe. (United States)

    Waldvogel, Siegfried R; Selt, Maximilian


    The power you're supplying: With the application of an optimized electrochemical approach, the allylic oxidation of olefins, which is an important C-H activation process that provides access to enones, becomes a sustainable, versatile, and potent key reaction for organic synthesis.

  1. 1-Allyl-5-chloroindoline-2,3-dione

    Directory of Open Access Journals (Sweden)

    Zineb Tribak


    Full Text Available In the title compound, C11H8ClNO2, the allyl side chain is almost perpendicular to the 5-chloroindoline-2,3-dione ring system, with a dihedral angle of 88.0 (3°. In the crystal, C—H...O interactions link the molecules into layers lying parallel to the bc plane.

  2. Pseudoprolines as removable turn inducers: tools for the cyclization of small peptides. (United States)

    Skropeta, Danielle; Jolliffe, Katrina A; Turner, Peter


    The cyclization of small peptides which do not incorporate turn inducers is often difficult. We have developed a method involving the use of removable turn inducers, in the form of pseudoprolines, for the cyclization of difficult peptide sequences. The pseudoprolines induce a cisoid amide bond in the peptide backbone which facilitates cyclization. They are then readily removed to yield a cyclic peptide that does not contain any turn inducers.

  3. Cyclization strategies to polyenes using Pd(II)-catalyzed couplings of pinacol vinylboronates. (United States)

    Iafe, Robert G; Chan, Daniel G; Kuo, Jonathan L; Boon, Byron A; Faizi, Darius J; Saga, Tomomi; Turner, Jonathan W; Merlic, Craig A


    As a complement to Pd(0)-catalyzed cyclizations, seven Pd(II)-catalyzed cyclization strategies are reported. α,ω-Diynes are selectively hydroborated to bis(boronate esters), which cyclize under Pd(II)-catalysis producing a diverse array of small, medium, and macrocyclic polyenes with controlled E,E, Z,Z, or E,Z stereochemistry. Various functional groups are tolerated including aryl bromides, and applications are illustrated.

  4. [Cu]-catalyzed domino Sonogashira coupling followed by intramolecular 5-exo-dig cyclization: synthesis of 1,3-dihydro-2-benzofurans. (United States)

    Mahendar, Lodi; Reddy, Alavala Gopi Krishna; Krishna, Jonnada; Satyanarayana, Gedu


    An efficient [Cu]-catalyzed domino Sonogashira coupling of o-bromobenzyl tertiary alcohols with terminal aryl acetylenes followed by an intramolecular anti-5-exo-dig cyclization is presented. The terminal aryl acetylenes were identified as ideal coupling partners that permit in situ intramolecular oxacyclization by the hydroxyl group as a pre-existing nucleophile of the alcohol. Notably, the intramolecular nucleophilic attack of the hydroxyl group took place on the alkyne moiety in a highly regio- and stereoselective manner. Interestingly, this method was amenable to a wide variety of o-bromobenzyl tertiary alcohols and furnished the corresponding cyclic ethers. On the other hand, when terminal alkyl acetylenes were used as the coupling partners, the reaction was impeded after the Sonogashira coupling.


    Kennedy, J.


    An ion exchange resin having a relatively high adsorption capacity tor uranyl ion as compared with many common cations is reported. The resin comprises an alphyl-allyl hydrogen phosphate polymer, the alphyl group being either allyl or a lower alkyl group having up to 5 carbon atoins. The resin is prepared by polymerizing compounds such as alkyl-diallyl phosphate and triallyl phosphate in the presence of a free radical generating substance and then partially hydrolyzing the resulting polymer to cause partial replacement of organic radicals by cations. A preferred free radical gencrating agent is dibenzoyl peroxide. The partial hydrolysis is brought about by refluxing the polymer with concentrated aqueous NaOH for three or four hours.

  6. Rh2(esp)2-catalyzed allylic and benzylic oxidations. (United States)

    Wang, Yi; Kuang, Yi; Wang, Yuanhua


    The dirhodium(II) catalyst Rh2(esp)2 allows direct solvent-free allylic and benzylic oxidations by T-HYDRO with a remarkably low catalyst loading. This method is operationally simple and scalable at ambient temperature without the use of any additives. The high catalyst stability in these reactions may be attributed to a dirhodium(II,II) catalyst resting state, which is less prone to decomposition.

  7. Experimental and Quantum-mechanical Investigation of the Vinylsilane-Iminium Ion Cyclization

    DEFF Research Database (Denmark)

    Kværnø, Lisbet; Norrby, Per-Ola; Tanner, David Ackland


    )-vinylsilanes cyclize via a silicon-stabilized b-carbocation, and that any formal aza-Cope rearrangement of the starting material to an allylsilane-iminium species does not take place in a concerted fashion. However, the calculations show that the aza-Cope rearrangement precedes cyclization for the corresponding (E...

  8. α-Carbonyl Radical Cyclization for the Total Synthesis of Natural Products

    Institute of Scientific and Technical Information of China (English)

    SHA Chin-Kang; CHIU Rei-Torng; LIH Shinn-Horng; SANTHOSH K. C.; CHANG Ching-Jung; TSENG Wei-Hong; HO Wen-Yueh


    @@ Intramolecular radical cyclization reactions are now used routinely to synthesize carbocyclic and heterocyclicstructures. We have reported that α-carbonyl radicals 1, generated from the corresponding iodo ketones or enones,underwent intramolecular radical cyclization smoothly to afford products 2. [1,2

  9. Total synthesis of (+/-)-cytisine via the intramolecular heck cyclization of activated N-alkyl glutarimides. (United States)

    Coe, J W


    [reaction:see text] A synthesis of racemic cytisine 1 has been developed utilizing an intramolecular Heck cyclization to prepare the bridged tricyclic intermediate 2. The cyclization employs activated glutarimide-derived ketene aminals 3 (X = P(O)OEt(2) or SO(2)CF(3)) and represents the first use of such intermediates in metal-catalyzed processes.

  10. An Unexpected Reaction of Allylic Propynoate under Palladium(Ⅱ) Catalysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Zhao-Guo(张兆国); LU,Xi-Yan(陆熙炎); LANG,Shen-Hui(郎深慧)


    Palladium (Ⅱ) catalyzed reactions of allyl propynoate in the presence of excess halide ions with or without allyl halide or acrolein were studied, yielding (E)-3-halo-2-allyl-acrylic acid as the sole product. A mechanism involving halopalladation, carbopalladation, ring opening and β-heteroatom elimination was prioposed and was further justified by the reaction with deuterated substrate.keywords palladium, enyne, halopalladation, carbopalladation,β-heteroatom elimination was proposed and was further justified by the reaction with deuterated substrate.

  11. Silver-Catalyzed Decarboxylative Allylation of Aliphatic Carboxylic Acids in Aqueous Solution. (United States)

    Cui, Lei; Chen, He; Liu, Chao; Li, Chaozhong


    Direct decarboxylative radical allylation of aliphatic carboxylic acids is described. With K2S2O8 as the oxidant and AgNO3 as the catalyst, the reactions of aliphatic carboxylic acids with allyl sulfones in aqueous CH3CN solution gave the corresponding alkenes in satisfactory yields under mild conditions. This site-specific allylation method is applicable to all primary, secondary, and tertiary alkyl acids and exhibits wide functional group compatibility.

  12. Allyl strontium compounds: synthesis, molecular structure and properties. (United States)

    Jochmann, Phillip; Davin, Julien P; Maslek, Stefanie; Spaniol, Thomas P; Sarazin, Yann; Carpentier, Jean-Francois; Okuda, Jun


    The synthesis and attempted isolation of neutral bis(allyl)strontium [Sr(C(3)H(5))(2)] (1) resulted in the isolation of potassium tris(allyl)strontiate K[Sr(C(3)H(5))(3)] (2). In situ generated 1 shows a pronounced Brønsted basicity, inducing polymerisation of THF. Ate complex 2 crystallises as [K(THF)(2){Sr(C(3)H(5))(3)}(THF)](∞) (2·(THF)(3)). The salt-like solid state structure of 2·(THF)(3) comprises a two-dimensional network of (μ(2)-η(3):η(3)-C(3)H(5))(-) bridged potassium and strontium centres. Synthesis of allyl complexes 1 and 2 utilised SrI(2), [Sr(TMDS)(2)] (3) (TMDS = tetramethyldisilazanide), and [Sr(HMDS)(2)] (HMDS = hexamethyldisilazanide) as strontium precursors. The solid state structure of previously reported [Sr(TMDS)(2)] (3) was established by X-ray single crystal analysis as a dissymmetric dimer of [Sr(2)(TMDS)(4)(THF)(3)] (3·(THF)(3)) with multiple Si-HSr agostic interactions. The presence of ether ligands (THF, 18-crown-6) influenced the Si-HSr resonances in the NMR spectra of the amido complex 3.

  13. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)


    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  14. Catalyst-free synthesis of skipped dienes from phosphorus ylides, allylic carbonates, and aldehydes via a one-pot SN2' allylation-Wittig strategy. (United States)

    Xu, Silong; Zhu, Shaoying; Shang, Jian; Zhang, Junjie; Tang, Yuhai; Dou, Jianwei


    A catalyst-free allylic alkylation of stabilized phosphorus ylides with allylic carbonates via a regioselective SN2' process is presented. Subsequent one-pot Wittig reaction with both aliphatic and aromatic aldehydes as well as ketenes provides structurally diverse skipped dienes (1,4-dienes) in generally high yields and moderate to excellent stereoselectivity with flexible substituent patterns. This one-pot SN2' allylation-Wittig strategy constitutes a convenient and efficient synthetic method for highly functionalized skipped dienes from readily available starting materials.

  15. Direct Substitution of the Hydroxy Group at the Allylic/propargylic Position with Carbon-and Heteroatomcentered Nucleophiles Catalyzed by Yb(OTf)3

    Institute of Scientific and Technical Information of China (English)

    HUANG Wen; SHEN Quan-Sheng; WANG Jia-Liang; ZHOU Xi-Geng


    An efficient and highly selective Yb(OTf)3-catalyzed direct substitution of the hydroxy group at the allylic and propargylic positions with a variety of heteroatom- and carbon-centered nucleophiles, such as alcohols, thiols,amines, amides and active methylene compounds has been developed. The advantages of the present catalytic system are wide availability of the starting materials, especially for tolerance to thiols, no need for dried solvents and additives, mild conditions, short time of reaction, simple manipulation and environmentally friendly catalyst that can be recovered and reused at least ten times without significant reduction of activity.

  16. Alcohol Alert (United States)

    ... main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & ... on a single aspect of alcohol abuse and alcoholism. Please click on the desired publication for full ...

  17. Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl-B(pin) Compounds to Ketones and α-Ketoesters. (United States)

    Robbins, Daniel W; Lee, KyungA; Silverio, Daniel L; Volkov, Alexey; Torker, Sebastian; Hoveyda, Amir H


    A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

  18. Proline-catalysed asymmetric ketol cyclizations: The template mechanism revisited

    Indian Academy of Sciences (India)

    R Malathi; D Rajagopal; Zoltan G Hajos; S Swaminathan


    A modified template mechanism based on modelling studies of energy minimised complexes is presented for the asymmetric proline-catalysed cyclization of triketones 1, 2 and 3 to the 2, 3-ketols 1a, 2a and 3a respectively. The template model involves a three-point contact as favoured in enzyme-substrate interactions. Our minimisation studies are in agreement with the divergent behaviour of the 6,5-, 6,6- and 6,7-bicyclic systems. They support the high 93.4% ee observed with the 6,5-bicyclic ketol and the lower 73% ee found with the 6,6-bicyclic ketol. The calculations also explain the lack of asymmetric induction with the 6,7-bicyclic system.

  19. Catalytic membrane-installed microchannel reactors for one-second allylic arylation. (United States)

    Yamada, Yoichi M A; Watanabe, Toshihiro; Torii, Kaoru; Uozumi, Yasuhiro


    A variety of catalytic membranes of palladium-complexes with linear polymer ligands were prepared inside a microchannel reactor via coordinative and ionic molecular convolution to provide catalytic membrane-installed microdevices, which were applied to the instantaneous allylic arylation reaction of allylic esters and aryl boron reagents under microflow conditions to afford the corresponding coupling products within 1 second of residence time.

  20. Copper-Catalyzed SN2'-Selective Allylic Substitution Reaction of gem-Diborylalkanes. (United States)

    Zhang, Zhen-Qi; Zhang, Ben; Lu, Xi; Liu, Jing-Hui; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao


    A Cu/(NHC)-catalyzed SN2'-selective substitution reaction of allylic electrophiles with gem-diborylalkanes is reported. Different substituted gem-diborylalkanes and allylic electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. The asymmetric version of this reaction was initially researched with chiral N-heterocyclic carbene (NHC) ligands.

  1. Allyl sulphides in olefin metathesis: catalyst considerations and traceless promotion of ring-closing metathesis. (United States)

    Edwards, Grant A; Culp, Phillip A; Chalker, Justin M


    Allyl sulphides are reactive substrates in ruthenium-catalysed olefin metathesis reactions, provided each substrate is matched with a suitable catalyst. A profile of catalyst activity is described, along with the first demonstration of allyl sulphides as traceless promoters in relayed ring-closing metathesis reactions.

  2. Memory effects in palladium-catalyzed allylic Alkylations of 2-cyclohexen-1-yl acetate

    DEFF Research Database (Denmark)

    Svensen, Nina; Fristrup, Peter; Tanner, David Ackland;


    The objective of this work was to characterize the enantiospecificity of the allylic alkylation of enantioenriched 2-cyclohexen-1-yl acetate with the enolate ion of dimethyl malonate catalyzed by unsymmetrical palladium catalysts. The precatalysts employed were (eta(3)-allyl)PdLCl, where L is a m...

  3. Corn oil and milk enhance the absorption of orally administered allyl isothiocyanate in rats. (United States)

    Ippoushi, Katsunari; Ueda, Hiroshi; Takeuchi, Atsuko


    Allyl isothiocyanate, a chief component of mustard oil, exhibits anticancer effects in both cultured cancer cells and animal models. The accumulation of the N-acetylcysteine conjugate of allyl isothiocyanate, the final metabolite of allyl isothiocyanate, in urine was evaluated in rats that were orally coadministered allyl isothiocyanate with fluids (e.g., water, green tea, milk, and 10% ethanol) or corn oil. The N-acetylcysteine conjugate of allyl isothiocyanate content in urine when allyl isothiocyanate (2 or 4μmol) was coadministered with corn oil or milk showed a greater increase (1.4±0.22 or 2.7±0.34μmol or 1.2±0.32 or 2.5±0.36μmol, 1.6- to 1.8-fold or 1.5-fold, respectively) than when allyl isothiocyanate (2 or 4μmol) was coadministered with water (0.78±0.10 or 1.7±0.17μmol). This result demonstrates that corn oil and milk enhance the absorption of allyl isothiocyanate in rats.

  4. Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

    Directory of Open Access Journals (Sweden)

    Florian Boeck


    Full Text Available (E-Alkyl ortho-hydroxycinnamates cyclize to coumarins at elevated temperatures of 140–250 °C. We find that the use of tri-n-butylphosphane (20 mol % as a nucleophilic organocatalyst in MeOH solution allows cyclization to take place under much milder conditions (60–70 °C. Several coumarins were prepared, starting from ortho-hydroxyarylaldehydes, by Wittig reaction with Ph3P=CHCO2Me to (E-methyl ortho-hydroxycinnamates, followed by the phosphane catalyzed cyclization.

  5. Autocatalytic cyclization of an excised intervening sequence RNA is a cleavage-ligation reaction. (United States)

    Zaug, A J; Grabowski, P J; Cech, T R

    The intervening sequence (IVS) of the Tetrahymena ribosomal RNA precursor is excised as a linear RNA molecule which subsequently cyclizes itself in a protein-independent reaction. Cyclization involves cleavage of the linear IVS RNA 15 nucleotides from its 5' end and formation of a phosphodiester bond between the new 5' phosphate and the original 3'-hydroxyl terminus of the IVS. This recombination mechanism is analogous to that by which splicing of the precursor RNA is achieved. The circular molecules appear to have no direct function in RNA splicing, and we propose the cyclization serves to prevent unwanted RNA from driving the splicing reactions backwards.

  6. Green Synthesis and Regioselective Control of Sn/I2 Mediated Allylation of Carbonyl Compounds with Crotyl Halide in Water

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Yan; ZHA,Zhang-Gen; ZHOU,Yu-Qing; WANG,Zhi-Yong


    @@ Barbier-type carbonyl allylation is particularly useful due to ease of operation and the availability and tractability of allylic substrates,[1] Metals such as indium, zinc and tin are often used as the mediator. Here we present a green approach toward the synthesis, that is, Sn/I2 mediated allylation of carbonyl compounds with crotyl halide in water.

  7. Release and antibacterial activity of allyl isothiocyanate/β-cyclodextrin complex encapsulated in electrospun nanofibers. (United States)

    Aytac, Zeynep; Dogan, Sema Y; Tekinay, Turgay; Uyar, Tamer


    Allyl isothiocyanate (AITC) is known as an efficient antibacterial agent but it has a very high volatility. Herein, AITC and AITC/β-cyclodextrin (CD)-inclusion complex (IC) incorporated in polyvinyl alcohol (PVA) nanofibers were produced via electrospinning. SEM images elucidated that incorporation of AITC and AITC/β-CD-IC into polymer matrix did not affect the bead-free fiber morphology of PVA nanofibers. (1)H-NMR and headspace GC-MS analyses revealed that very low amount of AITC was remained in PVA/AITC-NF because of the rapid evaporation of AITC during the electrospinning process. Nevertheless, much higher amount of AITC was preserved in the PVA/AITC/β-CD-IC-NF due to the CD inclusion complexation. The sustained release of AITC from nanofibers was evaluated at 30°C, 50°C and 75°C via headspace GC-MS. When compared to PVA/AITC-NF, PVA/AITC/β-CD-IC-NF has shown higher antibacterial activity against Escherichia coli and Staphylococcus aureus due to the presence of higher amount of AITC in this sample which was preserved by CD-IC.

  8. Construction of an Asymmetric Quaternary Carbon Center via Allylation of Hydrazones

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Bum; Satyender, Apuri; Jang, Doo Ok [Yonsei Univ., Wonju (Korea, Republic of)


    Asymmetric indium-mediated allylation of imine derivatives bearing a chiral auxiliary is a reliable strategy for the synthesis of chiral homoallylic amines. Various techniques for indium-mediated stereoselective allylation of imines bearing a chiral auxiliary have been reported. In 1997 Loh and co-workers reported indium-mediated allylation with imines derived from L-valine methyl ester. Since then, many forms of indium-mediated allylation bearing a chiral auxiliary have been reported, including imines derived from (S)-valinol, (R)-phenylglycinol, uracil, (R)-phenylglycinol methyl ester, N-tert-butanesufinamide, and (1R,2S)-1-amino-2-indanol. However, the synthesis of chiral auxiliaries often involves a laborious multi-step synthesis with expensive reagents. Therefore, the development of readily accessible chiral auxiliaries for asymmetric indium-mediated all-ylation is in high demand.

  9. Tungstosilicic Acid: An Efficient and Ecofriendly Catalyst for the Conversion of Alcohols to Alkyl Iodides

    Directory of Open Access Journals (Sweden)

    Masoud Mokhtary


    Full Text Available Treatment of a range of benzylic, allylic, and secondary aliphatic alcohols with potassium iodides in the presence of H4SiW12O40 affords the corresponding alkyl iodides in good to excellent yield with straightforward purification at room temperature in CH3CN.

  10. Polymer-support Selenium-induced Electrophilic Cyclization: Solid-phase Synthesis of Flavonoids

    Institute of Scientific and Technical Information of China (English)

    Jian CAO; E TANG; Xuan HUANG; Lu Ling WU; Xian HUANG


    The Lewis acid mediated polystyrene supported selenium induced intramolecular cyclization of chalcones and oxidative cleavage of selenium resins gave the corresponding flavonoids in good yields and purities have been reported.

  11. The Total Synthesis of 14-Deoxycrassin and Pseudoplexaurol: A Convergent Synthesis of Cyclization Precursor

    Institute of Scientific and Technical Information of China (English)


    The synthesis of epoxy aldehyde 4, a cyclization precursor for the total synthesis of 14-deoxycrassin and pseudoplexaurol, starting from geraniol in a convergent and stereoselective manner, is described.

  12. Palladium-catalyzed Cascade Cyclization-Coupling Reaction of Benzyl Halides with N,N-Diallylbenzoylamide

    Institute of Scientific and Technical Information of China (English)

    Yi Min HU; Yu ZHANG; Jian Lin HAN; Cheng Jian ZHU; Yi PAN


    A novel type of palladium-catalyzed cascade cyclization-coupling reaction has been found. Reaction of N, N-diallylbenzoylamide 1 with benzyl halides 2 afforded the corresponding dihydropyrroles 3 in moderate to excellent yields.

  13. Do garlic-derived allyl sulfides scavenge peroxyl radicals? (United States)

    Amorati, Riccardo; Pedulli, Gian Franco


    The chain-breaking antioxidant activities of two garlic-derived allyl sulfides, i.e. diallyl disulfide (1), the main component of steam-distilled garlic oil, and allyl methyl sulfide (3) were evaluated by studying the thermally initiated autoxidation of cumene or styrene in their presence. Although the rate of cumene oxidation was reduced by addition of both 1 and 3, the dependence on the concentration of the two sulfides could not be explained on the basis of the classic antioxidant mechanism as with phenolic antioxidants. The rate of oxidation of styrene, on the other hand, did not show significant changes upon addition of either 1 or 3. This unusual behaviour was explained in terms of the co-oxidant effect, consisting in the decrease of the autoxidation rate of a substrate forming tertiary peroxyl radicals (i.e. cumene) upon addition of little amounts of a second oxidizable substrate giving rise instead to secondary peroxyl radicals. The relevant rate constants for the reaction of ROO(.) with 1 and 3 were measured as 1.6 and 1.0 M(-1) s(-1), respectively, fully consistent with the H-atom abstraction from substituted sulfides. It is therefore concluded that sulfides 1 and 3 do not scavenge peroxyl radicals and therefore cannot be considered chain-breaking antioxidants.

  14. Synthesis and mechanism of formation of oxadeazaflavines by microwave thermal cyclization of ortho-halobenzylidene barbiturates

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa-Villar, J. Daniel; Oliveira, Sandra C.G. de, E-mail: [Grupo de Quimica Medicinal, Departamento de Quimica, Instituto Militar de Engenharia, Rio de Janeiro, RJ (Brazil)


    The thermal cyclization reaction of o-halobenzylidene barbiturates was developed as an efficient and simple method for the preparation of oxadeazaflavines. The use of solid state reaction conditions with microwave irradiation afforded the products in 5 min with 47 to 98% yield. Experimental synthetic results and thermogravimetric reaction analyses agree with the molecular modeling mechanism simulation, indicating that this reaction occurs through an intramolecular hetero-Diels-Alder cyclization followed by fast re-aromatization. (author)

  15. Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution. (United States)

    Bu, Xianzhang; Wu, Xiaoming; Xie, Guiyang; Guo, Zhihong


    [reaction: see text] Head-to-tail cyclization of peptides is a multistep process involving tedious C-terminal activation and side chain protection. Here we report a facile, quantitative cyclization method in aqueous ammonia solution for the total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its analogues from their fully deprotected linear thioester precursors on a solid support. This novel aqueous method is conformation-dependent and may be applicable to syntheses of other natural cyclic peptides.

  16. Organic Photocatalytic Cyclization of Polyenes: A Visible-Light-Mediated Radical Cascade Approach. (United States)

    Yang, Zhongbo; Li, Han; Zhang, Long; Zhang, Ming-Tian; Cheng, Jin-Pei; Luo, Sanzhong


    A visible-light-mediated, organic photocatalytic stereoselective radical cascade cyclization of polyprenoids is described. The desired cascade cyclization products are achieved in good yields and high stereoselectivities with eosin Y as photocatalyst in hexafluoro-2-propanol. The catalyst system is also suitable for 1,3-dicarbonyl compounds, which require only catalytic amounts of LiBr to promote the formation of the corresponding enols.

  17. T4 DNA ligase is more than an effective trap of cyclized dsDNA. (United States)

    Yuan, Chongli; Lou, Xiong Wen; Rhoades, Elizabeth; Chen, Huimin; Archer, Lynden A


    T4 DNA ligase is used in standard cyclization assays to trap double-stranded DNA (dsDNA) in low-probability, cyclic or highly bent conformations. The cyclization probability, deduced from the relative yield of cyclized product, can be used in conjunction with statistical mechanical models to extract the bending stiffness of dsDNA. By inserting the base analog 2-aminopurine (2-AP) at designated positions in 89 bp and 94 bp dsDNA fragments, we find that T4 DNA ligase can have a previously unknown effect. Specifically, we observe that addition of T4 ligase to dsDNA in proportions comparable to what is used in the cyclization assay leads to a significant increase in fluorescence from 2-AP. This effect is believed to originate from stabilization of local base-pair opening by formation of transient DNA-ligase complexes. Non-specific binding of T4 ligase to dsDNA is also confirmed using fluorescence correlation spectroscopy (FCS) experiments, which reveal a systematic reduction of dsDNA diffusivity in the presence of ligase. ATP competes with regular DNA for non-covalent binding to the T4 ligase and is found to significantly reduce DNA-ligase complexation. For short dsDNA fragments, however, the population of DNA-ligase complexes at typical ATP concentrations used in DNA cyclization studies is determined to be large enough to dominate the cyclization reaction.

  18. Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C., E-mail: [Beckman Research Institute of City of Hope, 1710 Flower Street, Duarte, CA 91010 (United States)


    An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex.

  19. Is an iodine atom almighty as a leaving group for Bu(3)SnH-mediated radical cyclization? The effect of a halogen atom on the 5-endo-trig radical cyclization of N-vinyl-alpha-halo amides. (United States)

    Tamura, Osamu; Matsukida, Hana; Toyao, Atsushi; Takeda, Yoshifumi; Ishibashi, Hiroyuki


    The effect of a halogen atom as a leaving group on Bu(3)SnH-mediated 5-endo-trig radical cyclization of N-(cyclohex-1-enyl) alpha-halo amides was examined. The cyclization of alpha-chloro amides occurred with a high degree of efficiency, whereas the corresponding alpha-iodo congeners gave only limited quantities of cyclization products. A detailed study revealed that these phenomena could be attributed to the initial conformations of alpha-halo amides. The cyclizing ability of alpha-iodo amides can be restored with Bu(3)SnCl or Bu(3)SnF as an additive. The cyclization of an alpha-iodo amide in the presence of Bu(3)SnF could be applied to a short-step synthesis of lycoranes featuring sequential 5-endo-trig and 6-endo-trig radical cyclizations.

  20. Alcohol Intolerance (United States)

    ... beer-alcohol.aspx. Accessed Jan. 16, 2015. Alcohol angioedema and uticaria. American Academy of Allergy, Asthma & Immunology. Accessed Jan. 16, 2015. Alcohol and ...

  1. Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter


    We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso......Asp and Asp. Detailed analysis using synthetic peptides confirmed that the cyclization forms between the N-terminus and its neighboring Asn residue, and the reaction shares the same succinimide intermediate with the Asn deamidation event. As a result, we, here, propose a molecular mechanism for this specific...

  2. Highly stereoselective synthesis of functionalized 1,3-dienes from a new allyl bromide

    Directory of Open Access Journals (Sweden)

    Asma Fray


    Full Text Available New and highly functionalized 1,3-dienes 3 and 4 have been synthesized via two different pathways starting from allyl bromide 1. Firstly, the reaction of allyl bromide 1 with triethylphosphite leads to an allylphosphonate 2, which undergoes the Wittig-Horner reaction with a range of saturated and unsaturated aldehydes gives rise to the corresponding 1,3-dienes 3. Secondly, a highly stereoselective reaction between allyl bromide 1 and nitroalkane salts, offers the possibility to obtaining functionalized (E-1,3-dienes 4.

  3. Engineering yield and rate of reductive biotransformation in Escherichia coli by partial cyclization of the pentose phosphate pathway and PTS-independent glucose transport. (United States)

    Siedler, Solvej; Bringer, Stephanie; Blank, Lars M; Bott, Michael


    Optimization of yields and productivities in reductive whole-cell biotransformations is an important issue for the industrial application of such processes. In a recent study with Escherichia coli, we analyzed the reduction of the prochiral β-ketoester methyl acetoacetate by an R-specific alcohol dehydrogenase (ADH) to the chiral hydroxy ester (R)-methyl 3-hydroxybutyrate (MHB) using glucose as substrate for the generation of NADPH. Deletion of the phosphofructokinase gene pfkA almost doubled the yield to 4.8 mol MHB per mole of glucose, and it was assumed that this effect was due to a partial cyclization of the pentose phosphate pathway (PPP). Here, this partial cyclization was confirmed by (13)C metabolic flux analysis, which revealed a negative net flux from glucose 6-phosphate to fructose 6-phosphate catalyzed by phosphoglucose isomerase. For further process optimization, the genes encoding the glucose facilitator (glf) and glucokinase (glk) of Zymomonas mobilis were overexpressed in recombinant E. coli strains carrying ADH and deletions of either pgi (phosphoglucose isomerase), or pfkA, or pfkA plus pfkB. In all cases, the glucose uptake rate was increased (30-47%), and for strains Δpgi and ΔpfkA also, the specific MHB production rate was increased by 15% and 20%, respectively. The yield of the latter two strains slightly dropped by 11% and 6%, but was still 73% and 132% higher compared to the reference strain with intact pgi and pfkA genes and expressing glf and glk. Thus, metabolic engineering strategies are presented for improving yield and rate of reductive redox biocatalysis by partial cyclization of the PPP and by increasing glucose uptake, respectively.

  4. beta-Cyclodextrin production by simultaneous fermentation and cyclization. (United States)

    Lima, H O; De Moraes, F F; Zanin, G M


    Production of beta-cyclodextrin (CD) with high-dextrose equivalent (DE) starch hydrolysates by simultaneous fermentation and cyclization (SFC) gives higher yields than using only the enzyme CGTase, because fermentation eliminates glucose and maltose that inhibit CD production, while at the same time, produces ethanol that increases yield. A 10% (w/v) solution of cassava starch, liquefied with alpha-amylase, was incubated with CGTase using: only the enzyme, added ethanol (from 1 to 5%), and added yeast S. cerevisiae (12% w/v), plus nutrients, the latter being the SFC process. Reaction conditions were: 38 degrees C, pH 6.0, DE from 2 to 25, and 3.3 mL of CGTase/L. The yield of beta-CD has decreased with an increase in DE, and maximum reaction yields were found for DE equal to 3.54, reaching 5.6, 14.7, and 11.5 mM beta-CD, respectively. For an increase of DE, of approx 6 times (from 3.54 to 23.79), beta-CD yield decreased 6 times for the first, and second reaction media with 3% (v/v) ethanol, and only approx 3 times for SFC (from 11.5 to 3.73 mM), showing that this process is less sensitive to variations in the DE.

  5. Solvent-Dependent Pyranopterin Cyclization in Molybdenum Cofactor Model Complexes. (United States)

    Williams, Benjamin R; Gisewhite, Douglas; Kalinsky, Anna; Esmail, Alisha; Burgmayer, Sharon J Nieter


    The conserved pterin dithiolene ligand that coordinates molybdenum (Mo) in the cofactor (Moco) of mononuclear Mo enzymes can exist in both a tricyclic pyranopterin dithiolene form and as a bicyclic pterin-dithiolene form as observed in protein crystal structures of several bacterial molybdoenzymes. Interconversion between the tricyclic and bicyclic forms via pyran scission and cyclization has been hypothesized to play a role in the catalytic mechanism of Moco. Therefore, understanding the interconversion between the tricyclic and bicyclic forms, a type of ring-chain tautomerism, is an important aspect of study to understand its role in catalysis. In this study, equilibrium constants (K(eq)) as well as enthalpy, entropy, and free energy values are obtained for pyran ring tautomerism exhibited by two Moco model complexes, namely, (Et4N)[Tp*Mo(O)(S2BMOPP)] (1) and (Et4N)[Tp*Mo(O)(S2PEOPP)] (2), as a solvent-dependent equilibrium process. Keq values obtained from (1)H NMR data in seven deuterated solvents show a correlation between solvent polarity and tautomer form, where solvents with higher polarity parameters favor the pyran form.

  6. Gold-Catalyzed Cyclization Processes: Pivotal Avenues for Organic Synthesis. (United States)

    Kumar, Amit; Singh, Sukhdev; Sharma, Sunil K; Parmar, Virinder S; Van der Eycken, Erik V


    Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium-sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo-, regio-, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry.

  7. Targeting of single stranded oligonucleotides through metal-induced cyclization of short complementary strands : Targeting of single stranded oligonucleotides


    Freville, Fabrice; Richard, Tristan; Bathany, Katell; Moreau, Serge


    International audience; A new strategy to cyclize a short synthetic oligonucleotide on a DNA or a RNA target strand is described. This one relies on a metal-mediated cyclization of short synthetic oligonucleotides conjugated with two chelating 2,2':6',2”-terpyridine moieties at their 3' and 5' ends. Cyclization following metal addition (Zn2+, Fe2+) was demonstrated using UV monitored thermal denaturation experiments, mass spectrometry analysis and gel shift assays. NMR experiments were used t...

  8. Chemoselective allylation of ketones in ionic liquids containing sulfonate anions. (United States)

    Galletti, Paola; Moretti, Fabio; Samorì, Chiara; Tagliavini, Emilio


    The chemoselective addition of tetraallyltin to dialkyl, alkenyl-alkyl, and alkynyl-alkyl ketones can be performed with high yields in N-methyl-N-butylpyrrolidinium trifuoromethansulfonate (MBP-Tf). Other room temperature ionic liquids (RTILs) can also be successfully employed if some sulfonic acid is added. The reaction is very sensitive to the electronic properties of the substrate. Aryl alkyl ketones bearing electron-withdrawing substituents behave like dialkyl ketones and react promptly; on the contrary, electron-rich aryl alkyl ketones react sluggishly, which allows selective competitive allylation of dialkyl substrates to occur. The ionic liquid solvent can be easily recycled, which meets the green chemistry principles of selectivity and reuse of chemicals. NMR spectroscopic data support the formation of tin-triflate catalysts in situ.

  9. Aerobic Linear Allylic C-H Amination: Overcoming Benzoquinone Inhibition. (United States)

    Pattillo, Christopher C; Strambeanu, Iulia I; Calleja, Pilar; Vermeulen, Nicolaas A; Mizuno, Tomokazu; White, M Christina


    An efficient aerobic linear allylic C-H amination reaction is reported under palladium(II)/bis-sulfoxide/Brønsted base catalysis. The reaction operates under preparative, operationally simple conditions (1 equiv of olefin, 1 atm O2 or air) with reduced Pd(II)/bis-sulfoxide catalyst loadings while providing higher turnovers and product yields than systems employing stoichiometric benzoquinone (BQ) as the terminal oxidant. Pd(II)/BQ π-acidic interactions have been invoked in various catalytic processes and are often considered beneficial in promoting reductive functionalizations. When such electrophilic activation for functionalization is not needed, however, BQ at high concentrations may compete with crucial ligand (bis-sulfoxide) binding and inhibit catalysis. Kinetic studies reveal an inverse relationship between the reaction rate and the concentration of BQ, suggesting that BQ is acting as a ligand for Pd(II) which results in an inhibitory effect on catalysis.

  10. Synthesis of acrylic and allylic bifunctional cross-linking monomers derived from PET waste (United States)

    Cruz-Aguilar, A.; Herrera-González, A. M.; Vázquez-García, R. A.; Navarro-Rodríguez, D.; Coreño, J.


    An acrylic and two novel allylic monomers synthesized from bis (hydroxyethyl) terephthalate, BHET, are reported. This was obtained by glycolysis of post-consumer PET with boiling ethylene glycol. The bifunctional monomer bis(2-(acryloyloxy)ethyl) terephthalate was obtained from acryloyl chloride, while the allylic monomers 2-(((allyloxi)carbonyl)oxy) ethyl (2-hydroxyethyl) terephthalate and bis(2-(((allyloxi)carbonyl)oxy)ethyl) terephthalate, from allyl chloroformate. Cross-linking was studied in bulk polymerization using two different thermal initiators. Monomers were analyzed by means of 1H NMR and the cross-linked polymers by infrared spectroscopy. Gel content higher than 90% was obtained for the acrylic monomer. In the case of the mixture of the allylic monomers, the cross-linked polymer was 80 % using BPO initiator, being this mixture 24 times less reactive than the acrylic monomer.

  11. Biomarkers derived from heterolytic and homolytic cleavage of allylic hydroperoxides resulting from alkenone autoxidation

    Digital Repository Service at National Institute of Oceanography (India)

    Rontania, J.F.; Harji, R.; Volkmanc, J.K.

    , hydroxyacids and alkyldiols resulted from the reduction during the NaBH4 treatment of the corresponding aldehydes, ketoxyacids and ketoxyaldehydes formed from heterolytic or hemolytic cleavages of allylic hydroperoxyl groups resulting from the oxidation...

  12. Facile synthesis of allyl resinate monomer in an aqueous solution under microwave irradiation

    Indian Academy of Sciences (India)

    Yanju Lu; Mixia Wang; Zhendong Zhao; Yuxiang Chen; Shichao Xu; Jing Wang; Liangwu Bi


    We have developed a facile method for production of allyl resinate monomer (allyl rosin ester) via a phase transfer reaction under microwave irradiation. The synthesis of allyl resinate was conducted using allyl chloride and sodium resinate as starting materials in aqueous solution at 50°C for 30 min with a yield of 94.7%, which is 20% higher than conventional heating method. The products precipitated spontaneously from the aqueous phase after reaction, which significantly facilitated the subsequent separation of monomer products. The synthesized monomer product appeared as a viscous liquid, with a viscosity of 460 mPa·s at 25°C and a density of 1.0469 g/cm3. The physical and chemical properties suggested that the synthesized monomer has great potential for free radical polymerization.

  13. A New Route to Preparations of Silyl Ethers by Reactions of Silyl Triflimides with Alcohol or Ether

    Institute of Scientific and Technical Information of China (English)

    TANG Zi-Long


    A few of acyclic and cyclic silyl ethers were firstly synthesized in good yields by reactions of silyl triflimides with alcohol or ether. The corresponding silyl triflimides were easily produced by protodesilylation of phenyl or allyl silanes with HNTf2. All new compounds were characterized by 1H NMR, 13C NMR, MS, IR and HRMS.

  14. Cyclization strategies of meditopes: affinity and diffraction studies of meditope-Fab complexes. (United States)

    Bzymek, Krzysztof P; Ma, Yuelong; Avery, Kendra A; Horne, David A; Williams, John C


    Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic `pocket' and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope-Fab complex.

  15. Effect of allyl isothiocyanate on developmental toxicity in exposed Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    John Russell Williams


    Full Text Available The pungent natural compound allyl isothiocyanate isolated from the seeds of Cruciferous (Brassica plants such as mustard is reported to exhibit numerous beneficial health-promoting antimicrobial, antifungal, anticarcinogenic, cardioprotective, and neuroprotective properties. Because it is also reported to damage DNA and is toxic to aquatic organisms, the objective of the present study was to determine whether it possesses teratogenic properties. The frog embryo teratogenesis assay-Xenopus (FETAX was used to determine the following measures of developmental toxicity of the allyl isothiocyanate: (a 96-h LC50, defined as the median concentration causing 50% embryo lethality; (b 96-h EC50, defined as the median concentration causing 50% malformations of the surviving embryos; and (c teratogenic malformation index (TI, equal to 96-h LC50/96-h EC50. The quantitative results and the photographs of embryos before and after exposure suggest that allyl isothiocyanate seems to exhibit moderate teratogenic properties. The results also indicate differences in the toxicity of allyl isothiocyanate toward exposed embryos observed in the present study compared to reported adverse effects of allyl isothiocyanate in fish, rodents, and humans. The significance of the results for food safety and possible approaches to protect against adverse effects of allyl isothiocyanate are discussed.


    Institute of Scientific and Technical Information of China (English)

    Jie Liu; Feng Lian; Zhao-kun Ma; Jie-ying Liang


    Orientation of copolymer polyacrylonitrile (PAN) chains during their deformation prior to stabilization and the further effect on the stabilization were investigated in detail.Results reveal that the orientation of PAN chains presents a saturation point of 69.51% when the deformation ratio reaches approximately 1.07,meanwhile the cyclization rather than the oxidation has a stronger dependence on the orientation of PAN chains during stabilization.The cyclization is facilitated that the cyclization degree is increasing while the activation energy is decreasing obviously as a consequence of the developing orientation of PAN fibers before the saturation point; however,it is restrained during the further deformation of PAN fibers after the point.The resulting carbon fibers obtained from the PAN fibers prepared at the saturation point possess the highest mechanical properties of 4.07 GPa in tensile strength and 249.0 GPa in tensile modulus.

  17. Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

    Directory of Open Access Journals (Sweden)

    Jungho Jun


    Full Text Available Gold-catalyzed intermolecular couplings of sulfonylacetylenes with allyl ethers are reported. A cooperative polarization of alkynes both by a gold catalyst and a sulfonyl substituent resulted in an efficient intermolecular tandem carboalkoxylation. Reactions of linear allyl ethers are consistent with the [3,3]-sigmatropic rearrangement mechanism, while those of branched allyl ethers provided [3,3]- and [1,3]-rearrangement products through the formation of a tight ion–dipole pair.

  18. 40 CFR 721.990 - 1,4-Benzedicarboxylic acid, dimethyl ester, polymer with 1,4 - butanediol, cyclized. (United States)


    ... ester, polymer with 1,4 - butanediol, cyclized. 721.990 Section 721.990 Protection of Environment..., dimethyl ester, polymer with 1,4 - butanediol, cyclized. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,4-benzedicarboxylic acid, dimethyl...

  19. Lewis Acid-Promoted Mukaiyama Aldol-Prins (MAP) Cyclizations of Acetals, Ketals, α-Acetoxy Ethers, and Orthoformates. (United States)

    Gesinski, Michael R; Van Orden, Lori J; Rychnovsky, Scott D


    The Mukaiyama aldol-Prins (MAP) cyclization of acetals stereoselectively provided substituted tetrahydropyrans. The scope of the reaction has been expanded to include other electrophiles, including ketals and α-acetoxy ethers. Finally, a double MAP cyclization with orthoformates is described.

  20. Lewis Acid-Promoted Mukaiyama Aldol–Prins (MAP) Cyclizations of Acetals, Ketals, α-Acetoxy Ethers, and Orthoformates (United States)

    Gesinski, Michael R.; Van Orden, Lori J.; Rychnovsky, Scott D.


    The Mukaiyama aldol–Prins (MAP) cyclization of acetals stereoselectively provided substituted tetrahydropyrans. The scope of the reaction has been expanded to include other electrophiles, including ketals and α-acetoxy ethers. Finally, a double MAP cyclization with orthoformates is described. PMID:20936058

  1. Robust, Chiral, and Porous BINAP-Based Metal–Organic Frameworks for Highly Enantioselective Cyclization Reactions

    Energy Technology Data Exchange (ETDEWEB)

    Sawano, Takahiro; Thacker, Nathan C.; Lin, Zekai; McIsaac, Alexandra R.; Lin, Wenbin (UC)


    We report here the design of BINAP-based metal–organic frameworks and their postsynthetic metalation with Rh complexes to afford highly active and enantioselective single-site solid catalysts for the asymmetric cyclization reactions of 1,6-enynes. Robust, chiral, and porous Zr-MOFs of UiO topology, BINAP-MOF (I) or BINAP-dMOF (II), were prepared using purely BINAP-derived dicarboxylate linkers or by mixing BINAP-derived linkers with unfunctionalized dicarboxylate linkers, respectively. Upon metalation with Rh(nbd)2BF4 and [Rh(nbd)Cl]2/AgSbF6, the MOF precatalysts I·Rh(BF4) and I·Rh(SbF6) efficiently catalyzed highly enantioselective (up to 99% ee) reductive cyclization and Alder-ene cycloisomerization of 1,6-enynes, respectively. I·Rh catalysts afforded cyclization products at comparable enantiomeric excesses (ee’s) and 4–7 times higher catalytic activity than the homogeneous controls, likely a result of catalytic site isolation in the MOF which prevents bimolecular catalyst deactivation pathways. However, I·Rh is inactive in the more sterically encumbered Pauson–Khand reactions between 1,6-enynes and carbon monoxide. In contrast, with a more open structure, Rh-functionalized BINAP-dMOF, II·Rh, effectively catalyzed Pauson–Khand cyclization reactions between 1,6-enynes and carbon monoxide at 10 times higher activity than the homogeneous control. II·Rh was readily recovered and used three times in Pauson–Khand cyclization reactions without deterioration of yields or ee’s. Our work has expanded the scope of MOF-catalyzed asymmetric reactions and showed that the mixed linker strategy can effectively enlarge the open space around the catalytic active site to accommodate highly sterically demanding polycyclic metallocycle transition states/intermediates in asymmetric intramolecular cyclization reactions.

  2. Tandem Olefin Metathesis/Oxidative Cyclization: Synthesis of Tetrahydrofuran Diols from Simple Olefins. (United States)

    Dornan, Peter K; Lee, Daniel; Grubbs, Robert H


    A tandem olefin metathesis/oxidative cyclization has been developed to synthesize 2,5-disubstituted tetrahydrofuran (THF) diols in a stereocontrolled fashion from simple olefin precursors. The ruthenium metathesis catalyst is converted into an oxidation catalyst in the second step and is thus responsible for both catalytic steps. The stereochemistry of the 1,5-diene intermediate can be controlled through the choice of catalyst and the type of metathesis conducted. This olefin stereochemistry then controls the THF diol stereochemistry through a highly stereospecific oxidative cyclization.

  3. “Cation-Stitching Cascade”: exquisite control of terpene cyclization in cyclooctatin biosynthesis (United States)

    Sato, Hajime; Teramoto, Kazuya; Masumoto, Yui; Tezuka, Noriyuki; Sakai, Kenta; Ueda, Shota; Totsuka, Yusuke; Shinada, Tetsuro; Nishiyama, Makoto; Wang, Chao; Kuzuyama, Tomohisa; Uchiyama, Masanobu


    Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding the origin and mechanism of the selectivity of terpene cyclization is challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin biosynthesis by means of theoretical calculations combined with experimental methods. We show that the main framework of cyclooctatin is formed through domino-type carbocation transportation along the terpene chain, which we call a “cation-stitching cascade”, including multiple hydrogen-shifts and a ring rearrangement that elegantly determine the stereoselectivity.

  4. Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

    Directory of Open Access Journals (Sweden)

    Mostafa Kiamehr


    Full Text Available The cyclization of cyclohexane-1,3-diones with various substituted pyridinium salts afforded functionalized 8-oxa-10-aza-tricyclo[,7]trideca-2(7,11-dienes. The reaction proceeds by regioselective attack of the central carbon atom of the 1,3-dicarbonyl unit to 4-position of the pyridinium salt and subsequent cyclization by base-assisted proton migration and nucleophilic addition of the oxygen atom to the 2-position, as was elucidated by DFT computations. Fairly extensive screening of bases and additives revealed that the presence of potassium cations is essential for formation of the product.

  5. Selective synthesis of indazoles and indoles via triazene-alkyne cyclization switched by different metals. (United States)

    Fang, Yan; Wang, Chengming; Su, Shengqin; Yu, Haizhu; Huang, Yong


    We described two orthogonal heterocycle syntheses, where an arene bearing both an alkyne and a triazene functionality underwent two distinct cyclization pathways mediated by different transition metals. Starting from the same substrates, a synthesis of 2H-indazole was accomplished by a Cu(II) salt promoted oxidative cyclization, while 2-substituted indoles could be accessed via a Ag(I) salt mediated N-N bond cleavage. This method represents the first synthesis of indoles from alkynyl triazenes. Computational analysis was performed for both reaction pathways, supporting a Lewis acid role for Cu and a π-acid catalysis for Ag.

  6. Mesoporous Metal Complex–Silica Aerogels for Environmentally Friendly Amination of Allylic Alcohols


    Grau Atienza, Aida; Baeza, Alejandro; Serrano, Elena; Garcia-Martinez, Javier; Nájera Domingo, Carmen


    Two series of mesoporous hybrid iron(III) complex–silica aerogels were prepared in one-pot synthesis by using the sol–gel coordination chemistry approach. The use of the ligands 3-(2-aminoethylamino)propyltrimethoxysilane and 2-(diphenylphosphino)ethyltriethoxysilane, both with terminal triethoxysilyl groups, were used to incorporate metal complexes in situ into the framework of silica, through their co-condensation with a silicon alkoxide during the aerogel formation. This methodology yielde...

  7. SN2 reactions with allylic substrates--Trends in reactivity (United States)

    Ochran, Richard A.; Uggerud, Einar


    The gas-phase identity SN2 reactions of allylic substrates has been studied by systematic altering of the nucleophile/nucleofuge X, the remote substituent Y, and the number of methyl substituents at the reaction centre: X- + YCHCHCZ2X --> YCHCHCZ2X + X- (X = H, CH3, NH2, F, Cl; Y = F, OH, H, CHO, BH2; Z = H, CH3). Key regions of the potential energy surfaces have been explored by MP2, B3LYP, G3B3 and G3 calculations; the latter two methods providing accurate estimates of the reaction barrier. The calculations show that irrespective of theoretical level, for the second row of the periodic table (X = CH3, NH2, OH, and F), the tendency is that the barrier height decreases in going from left to right in agreement with the previously observed trend for identity SN2 reactions at methyl. The barrier height decreases by introduction a [pi] electron withdrawing substituents, Y, remote 6rom the reaction centre. The barrier height increases by introducing methyl groups (Z = CH3) next to the reaction centre, but the effect is less than half of that of changing the remote substituent from Y = CHO to Y = OH. The trends cannot be explained by simplified valence bond theory and are discussed in light of a simple electrostatic bonding model of the transition structure.

  8. Allyl isothiocyanate induced stress response in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Saini AkalRachna K


    Full Text Available Abstract Background Allyl isothiocyanate (AITC from mustard is cytotoxic; however the mechanism of its toxicity is unknown. We examined the effects of AITC on heat shock protein (HSP 70 expression in Caenorhabditis elegans. We also examined factors affecting the production of AITC from its precursor, sinigrin, a glucosinolate, in ground Brassica juncea cv. Vulcan seed as mustard has some potential as a biopesticide. Findings An assay to determine the concentration of AITC in ground mustard seed was improved to allow the measurement of AITC release in the first minutes after exposure of ground mustard seed to water. Using this assay, we determined that temperatures above 67°C decreased sinigrin conversion to AITC in hydrated ground B. juncea seed. A pH near 6.0 was found to be necessary for AITC release. RT-qPCR revealed no significant change in HSP70A mRNA expression at low concentrations of AITC ( 1.0 μM resulted in a four- to five-fold increase in expression. A HSP70 ELISA showed that AITC toxicity in C. elegans was ameliorated by the presence of ground seed from low sinigrin B. juncea cv. Arrid. Conclusions • AITC induced toxicity in C. elegans, as measured by HSP70 expression. • Conditions required for the conversion of sinigrin to AITC in ground B. juncea seed were determined. • The use of C. elegans as a bioassay to test AITC or mustard biopesticide efficacy is discussed.

  9. New amidines from intramolecular cyclization in triflic acid of nitroketene aminals with a tethered phenyl ring

    Indian Academy of Sciences (India)

    Soro Yaya; Bamba Fanté; Siaka Sorho; Coustard Jean-Marie; Adima A Augustin


    Nitroketene aminals with a tethered phenyl group underwent an intramolecular cyclization in trifluoromethanesulfonic acid to afford the corresponding N-(3-ethyl-hydrohydroxyiminobenzocycloalkenylidene) methylamine trifluoromethanesulfonate. The yields were fair to good excepted for the starting compound 1-[N-ethyl-N-(2-phenylethyl)amino]-1-methylamino-2-nitroethene.

  10. Solvent-free cyclization of linear dienes using olefin metathesis and the Thorpe-Ingold effect

    Energy Technology Data Exchange (ETDEWEB)

    Forbees, M.D.E.; Myers, T.L.; Maynard, H.D.; Schulz, G.R. (Univ. of North Carolina, Chapel Hill (United States)); Patton, J.T.; Smith, D.W. Jr.; Wagener, K.B. (Univ. of Florida, Gainesville (United States))


    The olefin metathesis reaction is of great synthetic utility in polymer chemistry. The recent development of ring-opening (ROMP) and acyclic diene (ADMET) metathesis polymerization reactions has opened new avenues for the synthesis of novel polymeric materials. Recently the authors used ADMET to synthesize several photochemically active poly(keto olefins) using the catalyst Mo(CHCMe[sub 2]Ph)(NAr)(OCMe(CF[sub 3])[sub 2])[sub 2] (Ar = 2,6-diisopropylphenyl) (1) developed by Schrock and co-workers in 1990. In the course of that work, they discovered that neat samples of highly substituted dienes will cyclize quantitatively via metathesis to give difunctional five- and seven-membered rings instead of the expected linear polymer. Examples of substituted diene cyclizations by metathesis even in the presence of a solvent are rare. Their systematic exploitation in organic synthesis has therefore been limited to two recent studies by Fu and Grubbs, who cyclized several substituted diene ethers, amines, and amides to unsaturated oxygen and nitrogen heterocycles. Cyclization of unsubstituted dienes in various solvents has been reported, but complete conversion occurred in only a few cases. Formation of cyclic alkene oligomers from back-biting during the ROMP reaction is also known. The reactions reported here are unusual in that they are intermolecular between catalyst and substrate, yet can give 100% yield of product solely from the monomer in the absence of solvent. 13 refs.

  11. Epimerization-free C-terminal peptide activation, elongation and cyclization

    NARCIS (Netherlands)

    Popović, S.


    C-terminal peptide activation and cyclization reactions are generally accompanied with epimerization (partial loss of C‐terminal stereointegrity). Therefore, the focus of this thesis was to develop epimerization-free methods for C-terminal peptide activation to enable C-terminal peptide elongation a

  12. Stereoselective synthesis of 2,3-disubstituted dihydrobenzofuran using alkyne Prins type cyclization to vinylogous carbonates

    Indian Academy of Sciences (India)

    Santosh J Gharpure; V Prasath


    An intramolecular, alkyne Prins type cyclization of vinylogous carbonates derived from -alkynyl phenols is developed for the stereoselective construction of trans-2,3-disubstituted dihydrobenzofuran derivatives. Strong Lewis acids like TMSOTf catalyse this reaction efficiently. The presence of mildly electron donating groups on aryl rings increases the efficiency of the reaction.

  13. Molecular Iodine-Mediated Cyclization of Tethered Heteroatom-Containing Alkenyl or Alkynyl Systems

    Directory of Open Access Journals (Sweden)

    Malose Jack Mphahlele


    Full Text Available Molecular iodine has established itself as a readily available and easy-to-handle electrophilic and oxidizing reagent used in various organic transformations. In this review attention is focused on the use of molecular iodine in promoting cyclization (iodocyclization and cyclodehydroiodination of tethered heteroatom-containing alkenyl or alkynyl systems.

  14. An Efficient Cationic Cyclization Approach for the Construction of Labdane Diterpenoid Decalin Ring Skeleton

    Institute of Scientific and Technical Information of China (English)

    Jin Hui YANG; Wei Dong Z.LI


    An effective approach for the construction of the decalin ring skeleton of labdane diterpenoids was developed based on a key biomimetic cationic polyene cyclization of an epoxy allylsilane precursor. The synthetic approach demonstrated here would be useful in the enantioselective and diastereoselective total synthesis of natural labdane diterpenoids in general.

  15. Enantioselective Cascade Cyclization/Protodemetalation of Polyenes with N3Pt(2+) Catalysts. (United States)

    Nguyen, Ha; Gagné, Michel R


    The combination of the N-based pincer ligand PyBOX with Pt(2+) leads to new catalysts for the enantioselective cycloisomerization of dienyl- and trienyl-ols. The mechanistic combination of electrophilic cyclization followed by rapid protodemetalation is surprising and leads to a powerful construct for developing new reactions.

  16. Studies on Synthesis of a Cycloheptapeptide and Effects of Different Metal Ions on the Cyclization

    Institute of Scientific and Technical Information of China (English)

    LIU,Mian(刘勉); YE,Yun-Hua(叶蕴华)


    A cyclic heptapeptide, c(Gly-Ile-Pro-Tyr-Ile-Ala-Ala), which was isolated and identified from Stellaria yunnanensis Franch (M), was synthesized by solution method for the first tine.Protected heptapeptide Z-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OBzl was synthesized with 3-(diethoxy-phosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) as a coupling reagent. After deprotection of benzyl and benzyloxycarbonyl groups, a free linear heptapeptide H-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OH was cyclized in DMF (2× 10-3 mol/L) in the presence of nine different metal ions, i.e., Li+, Na+, K+, Cs+, Mg2+, Ca2+,Ba2+, Ni2++ and Cr3+ respectively, using DEPBT as a coupling reagent. Univalent metal ion Cs + enhanced both the cyclization yield and cyclization rate of H-Gly-Ile- Pro-Tyr-Ile-Ala-AlaOH, while some bivalent metal ions, such as Mg2+, Ca2+ and Ni2+ decreased the yields of c (Gly-Ile-Pro-Tyr-Ile-Ala-Ala)drastically. Trivalent metal ion Cr3 + even inhibited the cyclization reaction completely.

  17. National Institute on Alcohol Abuse and Alcoholism (United States)

    Skip to main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use ...

  18. An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides. (United States)

    Dekorver, Kyle A; North, Troy D; Hsung, Richard P


    A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of α-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones.

  19. Allyl isothiocyanate sensitizes TRPV1 to heat stimulation. (United States)

    Alpizar, Yeranddy A; Boonen, Brett; Gees, Maarten; Sanchez, Alicia; Nilius, Bernd; Voets, Thomas; Talavera, Karel


    The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca(2+) imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current-voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca(2+) imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat.

  20. Synthesis and Triethylamine-catalyzed Cyclization Reaction of 4-Pentyne-1,3-dione System Having Various Substituents

    Institute of Scientific and Technical Information of China (English)

    KURODA,Hirofumi; IZAWA,Hironori


    4-Pentyne-1,3-dione system having various substituents was synthesized in two steps and the cyclization behavior of the obtained 1 ,3-dicarbonyl compounds was examined. y-Pyrones and 2-alkylidene-2,3-dihydro-3-fu-ranones were obtained by the triethylamine-catalyzed cyclization of the 4-pentyne-l,3-dione system having a dike-tone moiety. Furthermore, a phenol derivative was obtained in the case of 4-pentyne-1,3-dione system having an ester moiety. Thus, it was found that the kind of substituents in the 4-pentyne-1,3-dione system remarkably influenced the selectivity in the cyclization.

  1. Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

    Directory of Open Access Journals (Sweden)

    Antonio Monopoli


    Full Text Available The Pd–benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand is also proposed.

  2. Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles. (United States)

    Kljajic, Marko; Puschnig, Johannes G; Weber, Hansjörg; Breinbauer, Rolf


    An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement.

  3. Alcohol Abuse (United States)

    ... even small amounts of alcohol may hurt an unborn child)Drink alcohol while you are looking after ... shakes, being very suspicious), and can even include death. This is why you need your doctor’s care ...

  4. Highly enantio- and diastereoselective synthesis of β-methyl-γ- monofluoromethyl-substituted alcohols

    KAUST Repository

    Yang, Wenguo


    Enanatiopure β-methyl-γ-monofluoromethyl alcohols were prepared from the allylic alkylation between fluorobis(phenylsulfonyl)methane with Morita-Baylis-Hillman carbonates. The reaction was catalyzed by using the Cinchona alkaloid derivative, (DHQD)2AQN. The origin of the stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed stereoselectivity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Stereoselective Functionalization at C-2 and C-3 of the Gibberellin via an Intramolecular Free Radical Cyclization Approach

    Institute of Scientific and Technical Information of China (English)


    Stereoselective functionalization at C-2 and C-3 of the gibberellin skeleton was achieved via an intramolecular free radical cyclization approach using a tethered C-19 halomethyl ester as the radical precursor.

  6. Alcohol Test

    Institute of Scientific and Technical Information of China (English)


    The recent alcohol tax increase poses a challenge to China’s white spirits makers Alcohol, rather than wine, is an in-dispensable component to Chinese table culture. The financial crisis has failed to affect white spirits sales, but an alcohol tax increase might.

  7. Alcohol Poisoning (United States)

    ... t be awakened is at risk of dying. Alcohol poisoning is an emergency If you suspect that someone has alcohol poisoning — even if you don't see the ... immediately. Never assume the person will sleep off alcohol poisoning. Be prepared to provide information. If you ...

  8. SmI(2)-induced reductive cyclizations for the synthesis of cyclic ethers and applications in natural product synthesis. (United States)

    Nakata, Tadashi


    This tutorial review covers SmI(2)-induced reductive cyclizations of beta-alkoxyacrylate, beta-alkoxyvinyl sulfone, and beta-alkoxyvinyl sulfoxide, as methods for efficient construction of cyclic ethers. These cyclizations were developed as tools to aid in the total synthesis of marine polycyclic ethers, whose complex, synthetically challenging structures and potent bioactivities have attracted the attention of numerous synthetic organic chemists. Applications of the methods to total syntheses of various natural products containing cyclic ether are also described.

  9. Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

    Directory of Open Access Journals (Sweden)

    Hang Zhang


    Full Text Available The investigation of a Lewis base catalyzed asymmetric allylic amination of Morita–Baylis–Hillman carbonates derived from isatins afforded an electrophilic pathway to access multifunctional oxindoles bearing a C3-quaternary stereocenter, provided with good to excellent enantioselectivity (up to 94% ee and in high yields (up to 97%.

  10. Method of preparing water purification membranes. [polymerization of allyl amine as thin films in plasma discharge (United States)

    Hollahan, J. R.; Wydeven, T. J., Jr. (Inventor)


    Allyl amine and chemically related compounds are polymerized as thin films in the presence of a plasma discharge. The monomer compound can be polymerized by itself or in the presence of an additive gas to promote polymerization and act as a carrier. The polymerized films thus produced show outstanding advantages when used as reverse osmosis membranes.

  11. Facile Formation of Ytterbium Diiodide and Its Use in the Synthesis of Allyl Selenides

    Institute of Scientific and Technical Information of China (English)

    SU,Wei-Ke(苏为科); ZHANG,Yong-Min(张永敏); ZHENG,Yun-Fa(郑云法); LI,Yong-Shu(李永曙)


    Ytterbium metal reacts with iodine to generate ytterbium diiodide directly, which can react with diselenides to form ytterbium selenolates (RSeYbI2). These species reacted smoothly with allyl bromide to give allylselenides in moderate to good yields under neutral conditions.

  12. Combined experimental and theoretical mechanistic investigation of the Barbier allylation in aqueous media

    DEFF Research Database (Denmark)

    Dam, Johan Hygum; Fristrup, Peter; Madsen, Robert


    -determining step. For Zn, In, Sn, Sb, and Bi, an inverse secondary kinetic isotope effect was found (k(H)/k(D) = 0.75-0.95), which was compatible with the formation of a discrete organometallic species prior to allylation via a closed six-membered transition state. With Mg, a significantly larger build...

  13. Unusual selectivity-determining factors in the phosphine-free Heck arylation of allyl ethers

    DEFF Research Database (Denmark)

    Ambrogio, I.; Fabrizi, G.; Cacchi, S.


    The Heck reaction of aryl iodides and bromides with allyl ethers has been investigated. Using phosphinefree Pd(OAc)(2) in DNIF at 90 degrees C in the presence of Bu4NOAc, the reaction gave cinnamyl derivatives, usually in good to high yields, with a wide range of aryl halides. The reaction tolera...

  14. Zirconium-allyl complexes as resting states in zirconocene-catalyzed α-olefin polymerization. (United States)

    Panchenko, Valentina N; Babushkin, Dmitrii E; Brintzinger, Hans H


    UV-vis spectroscopic data indicate that zirconocene cations with Zr-bound allylic chain ends are generally formed during olefin polymerization with zirconocene catalysts. The rates and extent of their formation and of their re-conversion to the initial pre-catalyst cations depend on the types of zirconocene complexes and activators used.

  15. In(OTf)3 catalyzed allylation reaction of imines with tetraallyltin

    Institute of Scientific and Technical Information of China (English)

    Xiao Ning Wei; Ling Yan Liu; Bing Wang; Wei Xing Chang; Jing Li


    In the presence of catalytic amount of In(OTf)3 (10 mol%), a series of aldimines reacted with tetraallyltin in a 2:1 molar ratio to afford the corresponding homoallylic amines in good yields. The good atom efficiency was achieved under mild reaction conditions and a new protocol (allyl)4Sn/In(OTf)3 for simple imines was developed.

  16. Electrochemical studies and self diffusion coefficients in cyclic ammonium based ionic liquids with allyl substituents

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tzi-Yi [Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Polymer Materials, Kun Shan University, Tainan 71003, Taiwan (China); Su, Shyh-Gang [Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan (China); Wang, H. Paul [Department of Environmental Engineering, National Cheng Kung University, Tainan, Taiwan (China); Lin, Yuan-Chung [Institute of Environmental Engineering, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Gung, Shr-Tusen; Lin, Ming-Wei [Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan (China); Sun, I.-Wen, E-mail: [Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan (China)


    Research highlights: Cyclic ammonium-based ionic liquids with allyl substituent have high conductivity. Ionic liquids with allyl substituent have wide electrochemical window. Electrochemical and self diffusion coefficients are available for comparison. The Stokes-Einstein plots of DT{sup -1} vs. {eta}{sup -1} for redox couples in ILs are evaluated. Stokes-Einstein product of ferrocene is larger than that of cobaltocenium in ILs. - Abstract: Several cyclic ammonium-based ionic liquids (ILs) with allyl substituent are synthesized, these allyl substituent ILs have high ionic conductivity (up to 4.72 mS cm{sup -1} at 30 {sup o}C) and wide electrochemical window of 5 V. The electrochemical behaviors of two organometallic redox couples Fc/Fc{sup +} (ferrocene/ferrocenium) and Cc/Cc{sup +} (cobaltocene/cobaltocenium) have been studied in these ILs, the calculated Stokes-Einstein product (D{eta} T{sup -1}) of ferrocene in ILs is larger than that of cobaltocenium in ILs. The self-diffusion coefficients of cation and anion in these ILs are studied using pulsed gradient spin-echo NMR technique. There are very few reports where electrochemically derived diffusion coefficients and self diffusion coefficients are available for comparison, so a new key concept in electrochemistry could be developed in this paper.

  17. Palladium-catalyzed cross-coupling reactions of allylic halides and acetates with indium organometallics. (United States)

    Rodríguez, David; Pérez Sestelo, José; Sarandeses, Luis A


    The palladium(0)-catalyzed cross-coupling reaction of allylic halides and acetates with indium organometallics is reported. In this synthetic transformation, triorganoindium compounds and tetraorganoindates (aryl, alkenyl, and methyl) react with cinnamyl and geranyl halides and acetates to afford the S(N)2 product regioselectively and in good yield. The reaction proceeds with net inversion of the stereochemical configuration.

  18. Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions

    DEFF Research Database (Denmark)

    Pedersen, Torben Møller; Hansen, E. Louise; Kane, John


    A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different $alpha@-oxygen-substituted, racemic aldehydes were initially transformed...

  19. Surprisingly Mild Enolate-Counterion-Free Pd(0)-Catalyzed Intramolecular Allylic Alkylations

    DEFF Research Database (Denmark)

    Madec, David; Prestat, Guillaume; Martini, Elisabetta;


    Palladium-catalyzed intramolecular allylic alkylations of unsaturated EWG-activated amides can take place under phase-transfer conditions or in the presence of a crown ether. These new reaction conditions are milder and higher yielding than those previously reported. A rationalization for such an...

  20. A Novel, One-Step Palladium and Phenylsilane Activated Amidation from Allyl Ester on Solid Support

    Directory of Open Access Journals (Sweden)

    Zheming Ruan


    Full Text Available The direct conversion of solid-supported carboxylic acid allyl esters to carboxamides through the use of phenylsilane and catalytic Pd(PPh34 under mild reaction conditions is reported. The use of this methodology for the generation of a 48 compound solid-phase array is described herein.

  1. Catalytic allylation of phenols : chloride-free route towards epoxy resins

    NARCIS (Netherlands)

    Rijn, Jimmy Antonius van


    An industrially applicable process was developed for the synthesis of epoxy resin components. A catalytic reaction was explored towards allyl phenyl ethers that prevents the use of chloride-containing starting materials and thus formation of chloride-containing side products. The preferred allylatin

  2. Copper-catalyzed asymmetric allylic substitution reactions with organozinc and Grignard reagents

    NARCIS (Netherlands)

    Geurts, Koen; Fletcher, Stephen P.; van Zijl, Anthoni W.; Minnaard, Adriaan J.; Feringa, Ben L.; Bignall, H. E.; Jauncey, D. L.; Lovell, J. E. J.; Tzioumis, A. K.; Kedziora-Chudczer, L. L.; MacQuart, J. P.; Tingay, S. J.; Rayner, D. P.; Clay, R. W.


    Asymmetric allylic alkylations (AAAs) are among the most powerful C-C bond-forming reactions. We present a brief overview of copper-catalyzed AAAs with organometallic reagents and discuss our own contributions to this field. Work with zinc reagents and phosphoramidite ligands provided a framework fo

  3. Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides. (United States)

    Ames, Brian Douglas; Korman, Tyler Paz; Zhang, Wenjun; Smith, Peter; Vu, Thanh; Tang, Yi; Tsai, Shiou-Chuan


    Polyketides are a class of natural products with highly diverse chemical structures and pharmaceutical activities. Polyketide cyclization, promoted by the aromatase/cyclase (ARO/CYC), helps diversify aromatic polyketides. How the ARO/CYC promotes highly specific cyclization is not well understood because of the lack of a first-ring ARO/CYC structure. The 1.9 A crystal structure of Tcm ARO/CYC reveals that the enzyme belongs to the Bet v1-like superfamily (or STAR domain family) with a helix-grip fold, and contains a highly conserved interior pocket. Docking, mutagenesis, and an in vivo assay show that the size, shape, and composition of the pocket are important to orient and specifically fold the polyketide chain for C9-C14 first-ring and C7-C16 second-ring cyclizations. Two pocket residues, R69 and Y35, were found to be essential for promoting first- and second-ring cyclization specificity. Different pocket residue mutations affected the polyketide product distribution. A mechanism is proposed based on the structure-mutation-docking results. These results strongly suggest that the regiospecific cyclizations of the first two rings and subsequent aromatizations take place in the interior pocket. The chemical insights gleaned from this work pave the foundation toward defining the molecular rules for the ARO/CYC cyclization specificity, whose rational control will be important for future endeavors in the engineered biosynthesis of novel anticancer and antibiotic aromatic polyketides.

  4. Nucleophilic addition/double cyclization cascade processes between enynyl Fischer carbene complexes and alkynyl malonates. (United States)

    Álvarez-Fernández, Ana; Suárez-Rodríguez, Tatiana; Suárez-Sobrino, Ángel L


    Two new selective cascade processes for enynyl Fischer carbene complexes 1 are described in their reaction with alkynyl malonates. When carbene complexes 1 react with the sodium enolate of homopropargyl malonates 3 a consecutive Michael-type addition/cyclopentannulation/6-exo cyclization takes place leading, in a regio- and stereoselective way, to n/5/6 angular tricyclic compounds 5. Furthermore, when propargylic malonates are used, a delayed protonation of the reaction mixture allows intermediate 1,4-addition adduct Ia to evolve through a 5-exo cyclization, consisting of an intramolecular nucleophilic attack from the central carbon of the allenylmetallate over the triple C-C bond. Further spontaneous cyclopentannulation of the resulting metallatriene gives rise to bicyclic and linear polycyclic compounds 6 and 7, some of them bearing a polyquinane framework.

  5. Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization (United States)

    Johnston, Craig P.; Kothari, Abhishek; Sergeieva, Tetiana; Okovytyy, Sergiy I.; Jackson, Kelvin E.; Paton, Robert S.; Smith, Martin D.


    5-Endo-trig cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo-trig cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-endo-trig Michael reaction over the formally favoured 5-exo-trig Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions.

  6. One pot synthesis of 1-substituted tetrahydro--carbolines by Bischler–Napieralski cyclization

    Indian Academy of Sciences (India)

    Thokchom Prasanta Singh; Okram Mukherjee Singh


    A novel and facile one-pot synthesis of 1-substituted tetrahydro--carbolines by cyclocondensation of ketene ,–acetals with tryptamine in presence of InCl3 and TFA as co-catalysts by Bischler-Napieralski cyclization is described. The reaction involves formation of one C-N bond, one C-C bond and a new ring annulation over an indole moiety.

  7. Radical Oxidative Cyclization of Spiroacetals to Bis-spiroacetals: An Overview

    Directory of Open Access Journals (Sweden)

    Margaret A. Brimble


    Full Text Available The use of iodobenzene diacetate and iodine under photolytic conditions provides and efficient method for the oxidative cyclization of spiroacetals bearing an hydroxyalkyl side chain to bis-spiroacetals. An overview is provided of the use of this reaction for the synthesis of several bis-spiroacetal containing natural products such as the polyether antibiotics salinomycin and CP44,161 and the shellfish toxins, the spirolides.

  8. Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium-mediated SN2' cyclizations. (United States)

    Banfi, Luca; Basso, Andrea; Cerulli, Valentina; Guanti, Giuseppe; Riva, Renata


    A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO2Me) SN2' cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.

  9. Gold(I-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

    Directory of Open Access Journals (Sweden)

    Mathieu Morin


    Full Text Available Gold(I complexes have emerged as powerful and useful catalysts for the formation of new C–C, C–O and C–N bonds. Taking advantage of the specificity of [IPrAuNCMe][SbF6] complexes to favor the 5-exo-dig cyclization over the 6-endo-dig pathway, we report a high yielding and efficient method to generate substituted polyaromatic heterocycles under remarkably mild reaction conditions.

  10. Cyclization increases the antimicrobial activity and selectivity of arginine- and tryptophan-containing hexapeptides. (United States)

    Dathe, Margitta; Nikolenko, Heike; Klose, Jana; Bienert, Michael


    Arginine- and tryptophan-rich motifs have been identified in antimicrobial peptides with various secondary structures. We synthesized a set of linear hexapeptides derived from the sequence AcRRWWRF-NH(2) by substitution of tryptophan (W) by tyrosine (Y) or naphthylalanine (Nal) and by replacement of arginine (R) by lysine (K) to investigate the role of cationic charge and aromatic residues in membrane activity and selectivity. A second set of corresponding head-to-tail cyclic analogues was prepared to analyze the role of conformational constraints. The biological activity of the linear peptides followed the order Nal- > W- > Y-containing compounds and slightly decreased upon R-K substitution. A pronounced activity-improving and bacterial selectivity-enhancing effect was found upon cyclization of the R- and W-bearing parent peptide, whereas the activity-modifying effect of cyclization of Y- and Nal-containing peptides was low. The analysis of the driving forces of peptide interaction with model membranes showed that the activities correlated with the partition coefficients and the depths of peptide insertion into neutral and negatively charged lipid bilayers. Spectroscopic studies, RP-HPLC, and titration calorimetry implied that the combination of cationic and aromatic amino acid composition and conformational rigidity afforded a membrane-active, amphipathic structure with a highly charged face opposed by a cluster of aromatic side chains. However, threshold values of low and high hydrophobicity seemed to exist beyond which the activity-enhancing effect of cyclization was negligible. The results suggest that cyclization of small peptides of an appropriate amino acid composition may serve as a promising strategy in the design of antimicrobial peptides.

  11. α-Haloarylsulfonamides: Multiple Cyclization Pathways to Skeletally Diverse Benzofused Sultams


    Rayabarapu, Dinesh Kumar; Zhou, Aihua; Jeon, Kyu Ok; Samarakoon, Thiwanka; Rolfe, Alan; Siddiqui, Hina; Hanson, Paul R.


    The development of new methods to skeletally diverse sultams based on a central α-halo benzene sulfonamide building block is reported. Several salient features of this building block are utilized in multiple reaction pathways, including the Heck reaction, C- and O-arylation, Sonogashira-Pauson-Khand, Sonogashira-intramolecular hydroamination, lithiative cyclization and domino aza-Michael Heck for the generation of 5-, 6- and 7-membered benzofused bicyclic and tricyclic sultams.

  12. Enantioselective palladium-catalyzed dearomative cyclization for the efficient synthesis of terpenes and steroids. (United States)

    Du, Kang; Guo, Pan; Chen, Yuan; Cao, Zhen; Wang, Zheng; Tang, Wenjun


    A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (-)-totaradiol.

  13. Alcoholic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Gonzalo; Guzzo-Merello; Marta; Cobo-Marcos; Maria; Gallego-Delgado; Pablo; Garcia-Pavia


    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy(ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM.

  14. Synthesis, Characterization, and Some Properties of Cp*W(NO)(H)(η(3)-allyl) Complexes. (United States)

    Baillie, Rhett A; Holmes, Aaron S; Lefèvre, Guillaume P; Patrick, Brian O; Shree, Monica V; Wakeham, Russell J; Legzdins, Peter; Rosenfeld, Devon C


    Sequential treatment at low temperatures of Cp*W(NO)Cl2 in THF with 1 equiv of a binary magnesium allyl reagent, followed by an excess of LiBH4, affords three new Cp*W(NO)(H)(η(3)-allyl) complexes, namely, Cp*W(NO)(H)(η(3)-CH2CHCMe2) (1), Cp*W(NO)(H)(η(3)-CH2CHCHPh) (2), and Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3). Complexes 1-3 are isolable as air-stable, analytically pure yellow solids in good to moderate yields by chromatography or fractional crystallization. In solutions, complex 1 exists as two coordination isomers in an 83:17 ratio differing with respect to the endo/exo orientation of the allyl ligand. In contrast, complexes 2 and 3 each exist as four coordination isomers, all differing by the orientation of their allyl ligands which can have either an endo or an exo orientation with the phenyl or methyl groups being either proximal or distal to the nitrosyl ligand. A DFT computational analysis using the major isomer of Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3a) as the model complex has revealed that its lowest-energy thermal-decomposition pathway involves the intramolecular isomerization of 3a to the 16e η(2)-alkene complex, Cp*W(NO)(η(2)-CH2═CHCH2Me). Such η(2)-alkene complexes are isolable as their 18e PMe3 adducts when compounds 1-3 are thermolyzed in neat PMe3, the other organometallic products formed during these thermolyses being Cp*W(NO)(PMe3)2 (5) and, occasionally, Cp*W(NO)(H)(η(1)-allyl)(PMe3). All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by single-crystal X-ray crystallographic analyses.

  15. Role of Heavy Atom Tunneling in Myers-Saito Cyclization of Cyclic Enyne-Cumulene Systems. (United States)

    Karmakar, Sharmistha; Datta, Ayan


    Direct dynamics calculation using canonical variational transtition state theory (CVT) inclusive of small curvature tunneling (SCT) reveals heavy atom tunneling in Myers-Saito cyclization of 10- and 9-membered cyclic enyne-cumulene systems like 1,6-didehydro[10]annulene and derivative of neocarzinostatin, respectively. The pure density functional theory functional, BLYP at a 6-31+G (d,p) basis set reproduce the observed reaction energies and barriers within 1.0 kcal/mol. The calculated rate constants of cyclization inclusive of heavy atom tunneling (k(CVT+SCT) = 3.26 × 10(-4) s(-1) at 222 K; t1/2 = 35 min) are in excellent agreement with experiments (t1/2 ∼ 21-31 min). Both primary and secondary kinetic isotope effect (KIE) become enhanced significantly upon inclusion of quantum mechanical tunneling. An Arrhenius plot of KIE shows measurable curvature at the experimental temperature of 222 K. The translation vector for the cyclization reactions in the transition-states (TS) show significant motion of primary and secondary carbon atoms explaining the origin of large KIE.

  16. Deconvoluting the memory effect in Pd-catalyzed allylic alkylation; effect of leaving group and added chloride

    DEFF Research Database (Denmark)

    Fristrup, Peter; Jensen, Thomas; Hoppe, Jakob;


    An analysis of product distributions in the Tsuji-Trost reaction indicates that several instances of reported memory effects can be attributed to slow interconversion of the initially formed syn- and anti-[Pd(eta3-allyl)] complexes. Addition of chloride triggers a true memory effect, in which...... the allylic terminus originally bearing the leaving group has a higher reactivity. The latter effect, termed regioretention, can be rationalized by ionization from a palladium complex bearing a chloride ion, forming an unsymmetrically substituted [Pd(eta3-allyl)] complex. DFT calculations verify...

  17. Alcohol and pregnancy (United States)

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... When a pregnant woman drinks alcohol, the alcohol travels through her blood and into the baby's blood, tissues, and organs. Alcohol breaks down much more slowly in ...

  18. Utilizing redox-mediated Bergman cyclization toward the development of dual-action metalloenediyne therapeutics. (United States)

    Lindahl, Sarah E; Park, Hyunsoo; Pink, Maren; Zaleski, Jeffrey M


    Reaction of 2 equiv of 1,2-bis((diphenylphosphino)ethynyl)benzene (dppeb, 1) with Pt(cod)Cl2 followed by treatment with N2H4 yields the reduced Pt(0) metalloenediyne, Pt(dppeb)2, 2. This complex is stable to both air oxidation and metal-mediated Bergman cyclization under ambient conditions due to the nearly idealized tetrahedral geometry. Reaction of 2 with 1 equiv of I2 in the presence of excess 1,4-cyclohexadiene (1,4-CHD) radical trap rapidly and near-quantitatively generates the cis-Bergman-cyclized, diiodo product 3 ((31)P: δ = 41 ppm, J(Pt-P) = 3346 Hz) with concomitant loss of 1 equiv of uncyclized phosphine chelate ((31)P: δ = -33 ppm). In contrast, addition of 2 equiv of I2 in the absence of additional radical trap instantaneously forms a metastable Pt(dppeb)2(2+) intermediate species, 4, that is characterized by δ = 51 ppm in the (31)P NMR (J(Pt-P) = 3171 Hz) and ν(C≡C) = 2169 cm(-1) in the Raman profile, indicating that it is an uncyclized, bis-ligated complex. Over 24 h, 4 undergoes ligand exchange to form a neutral, square planar complex that spontaneously Bergman cyclizes at ambient temperature to give the crystalline product Pt(dppnap-I2)I2 (dppnap-I2 = (1,4-diiodonaphthalene-2,3-diyl)bis(diphenylphosphine)), 5, in 52% isolated yield. Computational analysis of the oxidation reaction proposes two plausible flattened tetrahedral structures for intermediate 4: one where the phosphine core has migrated to a trans-spanning chelate geometry, and a second, higher energy structure (3.3 kcal/mol) with two cis-chelating phosphine ligands (41° dihedral angle) via a restricted alkyne-terminal starting point. While the energies are disparate, the common theme in both structures is the elongated Pt-P bond lengths (>2.4 Å), indicating that nucleophilic ligand substitution by I(-) is on the reaction trajectory to the cyclized product 5. The efficiency of the redox-mediated Bergman cyclization reaction of this stable Pt(0) metalloenediyne prodrug and

  19. Synthetic Applications of Chiral Unsaturated Epoxy Alcohols Prepared by Sharpless Asymmetric Epoxidation

    Directory of Open Access Journals (Sweden)

    María Moreno


    Full Text Available An overview of the synthesis and applications of chiral 2,3-epoxy alcohols containing unsaturated chains is presented. One of the fundamental synthetic routes to these compounds is Sharpless asymmetric epoxidation, which is reliable, highly chemoselective and enables easy prediction of the product enantioselectivity. Thus, unsaturated epoxy alcohols are readily obtained by selective oxidation of the allylic double bond in the presence of other carbon-carbon double or triple bonds. The wide availability of epoxy alcohols with unsaturated chains, the versatility of the epoxy alcohol functionality (e.g. regio- and stereo-selective ring opening; oxidation; and reduction, and the arsenal of established alkene chemistries, make unsaturated epoxy alcohols powerful starting materials for the synthesis of complex targets such as biologically active molecules. The popularization of ring-closing metathesis has further increased their value, making them excellent precursors to cyclic compounds.

  20. From the tunneling dimer to the onset of microsolvation: Infrared spectroscopy of allyl radical water aggregates in helium nanodroplets (United States)

    Leicht, Daniel; Kaufmann, Matin; Pal, Nitish; Schwaab, Gerhard; Havenith, Martina


    The infrared spectrum of allyl:water clusters embedded in helium nanodroplets was recorded. Allyl radicals were produced by flash vacuum pyrolysis and trapped in helium droplets. Deuterated water was added to the doped droplets, and the infrared spectrum of the radical water aggregates was recorded in the frequency range 2570-2820 cm-1. Several absorption bands are observed and assigned to 1:1 and 1:2 allyl:D2O clusters, based on pressure dependent measurements and accompanying quantum chemical calculations. The analysis of the 1:1 cluster spectrum revealed a tunneling splitting as well as a combination band. For the 1:2 cluster, we observe a water dimer-like motif that is bound by one π-hydrogen bond to the allyl radical.

  1. Synthesis, characterization and evaluation of antioxidant and anticancer activities of novel benzisoxazole-substituted-allyl derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Anand, Mohanam [Kingston Engineering College, Vellore (India); Selvaraj, Vaithialingam [University College of Engineering-Villupuram, Villupuram (India); Alagar, Muthukaruppan [Anna University, Chennai (India)


    A novel series of various 2-allylbenzo[d]isoxazol-3(2H)-ones were synthesized using benzo[d]isoxazol-3(2H)-one treated with different allyl bromides/chlorides in the presence of water-mediated cesium carbonate as a new catalyst 3(a-h). The structures of the newly synthesized Benzisoxazole-substituted-allyl derivatives were characterized by spectroscopic methods and mass spectrometry. These synthesized compounds were evaluated for their in vitro antioxidant and anticancer activity. Compounds 3b, d, f, h were identified as the best hit against HT-29 Human colon cancer cells. Similarly, compounds like 3b, d, f, h showed significant antioxidant activity compared to the standard drug butylated hydroxy toluene (BHT)

  2. Recent Advances in the Application of Chiral Phosphine Ligands in Pd-Catalysed Asymmetric Allylic Alkylation

    Directory of Open Access Journals (Sweden)

    Erika Martin


    Full Text Available One of the most powerful approaches for the formation of simple and complex chiral molecules is the metal-catalysed asymmetric allylic alkylation. This reaction has been broadly studied with a great variety of substrates and nucleophiles under different reaction conditions and it has promoted the synthesis of new chiral ligands to be evaluated as asymmetric inductors. Although the mechanism as well as the active species equilibria are known, the performance of the catalytic system depends on the fine tuning of factors such as type of substrate, nucleophile nature, reaction medium, catalytic precursor and type of ligand used. Particularly interesting are chiral phosphines which have proved to be effective asymmetric inductors in several such reactions. The present review covers the application of phosphine-donor ligands in Pd-catalysed asymmetric allylic alkylation in the last decade.

  3. Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso-ene mechanism. (United States)

    Porter, David; Poon, Belinda M-L; Rutledge, Peter J


    Iron(II) complexes of the tetradentate amines tris(2-pyridylmethyl)amine (TPA) and N,N'-bis(2-pyridylmethyl)-N,N'-dimethylethane-1,2-diamine (BPMEN) are established catalysts of C-O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C-N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with either FeTPA (1 mol %) or FeBPMEN (10 mol %) converts cyclohexene to the allylic hydroxylamine (tert-butyl cyclohex-2-en-1-yl(hydroxy)carbamate) in moderate yields. Spectroscopic studies and trapping experiments suggest the reaction proceeds via a nitroso-ene mechanism, with involvement of a free N-Boc-nitroso intermediate. Asymmetric induction is not observed using the chiral tetramine ligand (+)-(2R,2'R)-1,1'-bis(2-pyridylmethyl)-2,2'-bipyrrolidine ((R,R')-PDP).

  4. [Surface modification of poly methyl methacrylate intraocular lens by alpha-allyl glucoside]. (United States)

    Qu, Chao; Yao, Ke; Kou, Ruiqiang; Xu, Zhikang


    A method for improving the biocompatibility of the intraocular lens (IOL) and reducing the cell attachment was adopted in this study. The alpha-Allyl glucoside was used for the surface modification of the poly methyl methacrylate (PMMA) IOL by way of plasma-induced in situ polymerization. The surfaces of the control and treatment IOLs were characterized by contact angle estimation and ESCA techniques. The resolution, diopter and anti-fatigue of loops were determined by physical and optical methods. Cell attachment on the surfaces was examined by light microscopy. The results indicated that all of the treatment groups had excellent physical and optical properties. The modification with the use of alpha-Allyl glucoside could improve the hydrophilicity of the anterior surface of the PMMA IOLs and reduce the cell attachment.

  5. Crystal structure of (E-3-allyl-2-sulfanylidene-5-[(thiophen-2-ylmethylidene]thiazolidin-4-one

    Directory of Open Access Journals (Sweden)

    Rahhal El Ajlaoui


    Full Text Available Molecules of the title compound, C11H9NOS3, are built up by one thiophene and one 2-thioxathiazolidin-4-one ring which are connected by a methylene bridge. In addition, there is an allyl substituent attached to nitrogen. The two rings are almost coplanar, making a dihedral angle between them of 0.76 (11°. The allyl group is oriented perpendicular to the mean plane through both ring systems. The crystal structure exhibits inversion dimers in which molecules are linked by pairs of C—H...O hydrogen bonds. Additional π–π interactions between neighboring thiophene and 2-thioxathiazolidin-4-one rings [intercentroid distance = 3.694 (2 Å] lead to the formation of a three-dimensional network.

  6. Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

    Directory of Open Access Journals (Sweden)

    Cox Liam R


    Full Text Available Abstract Background Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid-mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric β-silyloxy-α-methyl aldehydes, which contain an allylsilane tethered through the β-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. Results Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the α-site, affording only two of the four possible allylation products. Conclusion The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.. In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity.

  7. Synthesis of alkenyl boronates from allyl-substituted aromatics using an olefin cross-metathesis protocol. (United States)

    Hemelaere, Rémy; Carreaux, François; Carboni, Bertrand


    An efficient synthesis of 3-aryl-1-propenyl boronates from pinacol vinyl boronic ester and allyl-substituted aromatics by cross metathesis is reported. Although the allylbenzene derivatives are prone to isomerization reaction under metathesis conditions, we found that some ruthenium catalysts are effective for this methodology. This strategy thus provides an interesting alternative approach to alkyne hydroboration, leading to the preparation of unknown compounds. Moreover, the boron substituent can be replaced by various functional groups in good yields.

  8. On the key role of water in the allylic activation catalysed by Pd (II) bisphosphinite complexes

    Indian Academy of Sciences (India)

    Rakesh Kumar Sharma; Ashoka G Samuelson


    Palladium and platinum complexes of bisphosphinites and bisphosphines derived from mandelic acid have been prepared and characterized. Their ability to catalyze allylation of imines with allyltributylstannane has been studied. Bisphophinite complexes of Pd (II) are shown to be ideal and they work best in the presence of one equivalent of water. The near neutral conditions employed make the catalysts suitable for a wide variety of substrates.

  9. Improving the stability of alpha-conotoxin AuIB through N-to-C cyclization

    DEFF Research Database (Denmark)

    Armishaw, Christopher J; Jensen, Anders A; Balle, Lena D;


    Modification of alpha-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of alpha-conotoxin AuIB, a selective alpha3beta4 nicotinic...... acetylcholine receptor antagonist, to examine a range of oligopeptide linker lengths on the oxidative formation of disulfide bonds, activity at nicotinic acetylcholine receptors, and stability to degradation by chymotrypsin. Upon non-directed random oxidation, the ribbon isomer formed preferentially...

  10. Preparation and visible-light photocatalytic performances of cyclized polyacrylonitrile/TiO2 nanocomposites


    Wang, Xiaojing; Wang, Lin; Qingzhi LUO; Wang, Peng; Xu, Li; Desong WANG


    TiO2 nanomaterials were prepared by a conventional sol-gel method with tetrabutyl titanate as Ti source. The polyacrylonitrile solution with dimethyl sulfoxide as solvent was added into TiO2 sols to form TiO2 gels containing polyacrylonitrile, then the as-prepared TiO2 gels were heat-treated to prepare cyclized polyacrylonitrile/TiO2 (CPAN/TiO2) nanocomposites. The CPAN/TiO2 nanocomposites were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis diffuse re...

  11. Synthesis of anionic phosphorus-containing heterocycles by intramolecular cyclizations involving N-functionalized phosphinecarboxamides. (United States)

    Robinson, Thomas P; Goicoechea, Jose M


    We report that the 2-phosphaethynolate anion (PCO(-)) reacts with propargylamines in the presence of a proton source to afford novel N-derivatized phosphinecarboxamides bearing alkyne functionalities. Deprotonation of these species gives rise to novel five- and six-membered anionic heterocycles resulting from intramolecular nucleophilic attack of the resulting phosphide at the alkyne functionality (via 5-exo-dig or 6-endo-dig cyclizations, respectively). The nature of the substituents on the phosphinecarboxamide can be used to influence the outcome of these reactions. This strategy represents a unique approach to phosphorus-containing heterocylic systems that are closely related to known organic molecules with interesting bio-active properties.

  12. Raman spectroscopic approach to monitor the in vitro cyclization of creatine → creatinine (United States)

    Gangopadhyay, Debraj; Sharma, Poornima; Singh, Sachin Kumar; Singh, Pushkar; Tarcea, Nicolae; Deckert, Volker; Popp, Jürgen; Singh, Ranjan K.


    The creatine → creatinine cyclization, an important metabolic phenomenon has been initiated in vitro at acidic pH and studied through Raman spectroscopic and DFT approach. The equilibrium composition of neutral, zwitterionic and protonated microspecies of creatine has been monitored with time as the reaction proceeds. Time series Raman spectra show clear signature of creatinine formation at pH 3 after ∼240 min at room temperature and reaction is faster at higher temperature. The spectra at pH 1 and pH 5 do not show such signature up to 270 min implying faster reaction rate at pH 3.

  13. The direct oxidative diene cyclization and related reactions in natural product synthesis

    Directory of Open Access Journals (Sweden)

    Juliane Adrian


    Full Text Available The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (diastereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.

  14. Controlling both ground- and excited-state thermal barriers to Bergman cyclization with alkyne termini substitution. (United States)

    Nath, Mahendra; Pink, Maren; Zaleski, Jeffrey M


    The cross-coupling reaction of 2,3-dibromo-5,10,15,20-tetraphenylporphyrin with corresponding organostannanes in the presence of a Pd0 catalyst in THF at reflux temperature yields free base 2,3-dialkynylporphyrins 1a,c-e. The subsequent deprotection of trimethylsilyl group of 1a with TBAF in THF under aqueous conditions produces the 2,3-diethynyl-5,10,15,20-tetraphenylporphyrins 1b in 87% yield. Compounds 1a-d undergo zinc insertion upon treatment with Zn(OAc)2.2H2O in CHCl3/MeOH to give zinc(II) 2,3-dialkynyl-5,10,15,20-tetraphenylporphyrins (2a-d) in 70-92% yields. Thermal Bergman cyclization of 1a-e and 2a-d was studied in chlorobenzene and approximately 35-fold 1,4-cyclohexadiene at 120-210 degrees C. Compounds 1b and 2b with R = H react at lower temperature (120 degrees C) and produce cyclized products 3b and 4b in higher yields (65-70%) than their propyl, isopropyl, and phenyl analogues, with R = Ph being the most stable. Continuing in this trend, the -TMS derivatives 1a and 2a exhibit no reactivity even after heating at 190 degrees C in chlorobenzene/CHD for 24 h. Photolysis (at lambda >/= 395 nm) of 1b and 2b at 10 degrees C leads the formation of isolable picenoporphyrin products in 15 and 35% yields, respectively, in 72 h, whereas these compounds are stable in solution under same reaction conditions at 25 degrees C in the dark. Unlike thermolysis at 125 degrees C, which did not yield Bergman cyclized product for R = Ph, photolysis generated very small amounts of picenoporphyrin products (3c: 5%; 4c: 8% based on 1H NMR) as well as a mixture of reduced porphyrin products that were not separable. Thus, trends in the barrier to Bergman cyclization in the excited state exhibit the same trend as those observed in the ground state as a function of R-group. Finally, photolysis of 2b at 10 degrees C with lambda >/= 515 or 590 nm in benzene/iPrOH (4:1, 72 h) produces 4b in 15 and 6% isolated yields, indicating that conjugation of the enediyne unit into the

  15. Alcohol during Pregnancy (United States)

    ... Home > Pregnancy > Is it safe? > Alcohol during pregnancy Alcohol during pregnancy E-mail to a friend Please ... and fetal alcohol spectrum disorders. How does drinking alcohol during pregnancy affect your baby's health? Drinking alcohol ...

  16. Alcohol Energy Drinks (United States)

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 24018 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  17. Cyclization of farnesyl pyrophosphate to the sesquiterpene olefins humulene and caryophyllene by an enzyme system from sage (Salvia officinalis)

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.; Gundy, A.


    A soluble enzyme preparation obtained from sage (Salvia officinalis) leaves was shown to catalyze the divalent metal-ion dependent cyclization of trans, trans-farnesyl pyrophosphate to the macrocyclic sesquiterpene olefins humulene and caryophyllene. The identities of the biosynthetic products were confirmed by radiochromatographic analysis and by preparation of crystalline derivatives, and the specificity of labeling in the cyclization reaction was established by chemical degradation of the olefins derived enzymatically from (1-3H2)farnesyl pyrophosphate. These results constitute the first report on the cyclization of farnesyl pyrophosphate to humulene and caryophyllene, two of the most common sesquiterpenes in nature, and the first description of a soluble sesquiterpene cyclase to be isolated from leaves of a higher plant.

  18. Catalytic enantioselective reductions and allylations of prochiral ketones

    CERN Document Server

    Cunningham, A


    The use of LiGaH sub 4 in combination with the S,O-chelate 2-hydroxy-2'-mercapto-1,1'-binaphthyl (monothiobinaphthol, MTBH sub 2), forms an active catalyst (2 mol %) for the asymmetric reduction of prochiral ketones, when using catecholborane as the hydride source. This catalyst has successfully been applied to the enantioselective reduction of aryl/n-alkyl ketones, providing the chiral sec-alcohols in yields of 82 - 96% and with enantiomeric excess values of 59 - 93%. Alkyl/methyl ketones are reduced in yields of 72 - 93% and in 46 - 79% enantiomeric excess. Enantioface differentiation is on the basis of the steric requirements of the ketone substituents. The X-ray structure of the pre-catalyst, Li(THF) sub 3 Ga(MTB) sub 2 has been determined and in solution is in equilibrium with a dimeric species of constitution Li sub 2 Ga sub 2 (MTB) sub 4. An indium analogue whose X-ray structure was determined as Li sub 2 (THF) sub 5 lnCI(MTB) sub 2 has also been prepared. The indium- based catalyst does not form an en...

  19. Oxidative Dearomatization of 4,5,6,7-Tetrahydro-1H-indoles Obtained by Metal- and Solvent-Free Thermal 5-endo-dig Cyclization: The Route to Erythrina and Lycorine Alkaloids. (United States)

    Andreev, Ivan A; Ratmanova, Nina K; Novoselov, Anton M; Belov, Dmitry S; Seregina, Irina F; Kurkin, Alexander V


    A facile one-pot approach based on a thermally induced metal- and solvent-free 5-endo-dig cyclization reaction of the amino propargylic alcohols in combination with Dess-Martin periodinane-promoted oxidative dearomatization of 4,5,6,7-tetrahydroindole intermediates provides an efficient and robust access to 5,6-dihydro-1H-indol-2(4H)ones. Green, relatively mild and operationally simple characteristics of the synthetic sequence are the major advantages, which greatly amplify the developed methodology. The utility of obtained indolones as unified key precursors is demonstrated by the application of these products to the formal total syntheses of a whole pleiad of Erythrina- and Lycorine-type alkaloids, namely (±)-erysotramidine, (±)-erysotrine, (±)-erythravine, (±)-γ-lycorane, and abnormal erythrinanes (±)-coccoline and (±)-coccuvinine.

  20. Biomimetic cationic polyannulation reaction catalyzed by Bi(OTf)3: cyclization of 1,6-dienes, 1,6,10-trienes, and aryl polyenes. (United States)

    Godeau, Julien; Olivero, Sandra; Antoniotti, Sylvain; Duñach, Elisabet


    Nonactivated trienes and aryltrienes were cyclized into polycyclic compounds in good to excellent yields under bismuth triflate catalysis in a biomimetic fashion. The reaction showed broad applicability and allowed for the formation of functionalized bicyclic to tetracyclic structures from simple precursors in one pot. For some specific substrates, the cyclization was followed by a methyl shift as encountered in terpenoid biosynthesis.

  1. Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids (United States)

    Dzhons, Daria Yu


    Summary The base-mediated photochemical cyclization of 2-azidobenzoic acids with the formation of 2,1-benzisoxazole-3(1H)-ones is reported. The optimization and scope of this cyclization reaction is discussed. It is shown that an essential step of the ring closure of 2-azidobenzoic acids is the formation and photolysis of 2-azidobenzoate anions. PMID:27340478

  2. Rhodium-catalyzed selective[2+2+2]cyclizations of 1,6-diynes with monoynes leading to isoindolines and isobenzofurans

    Institute of Scientific and Technical Information of China (English)


    A highly efficient and selective[2+2+2]cyclization of diynes and monoalkynes was catalyzed by rhodium under room temperature in water/THF mixed solvent,affording isoindolines and isobenzofurans in good to excellent yields.The center atoms (N,O) in the diynes showed a significant effect for the cyclization.

  3. Biosynthesis of monoterpenes: Stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to camphane and isocamphane monoterpenes

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.; Gershenzon, J.; Wheeler, C.J.; Satterwhite, D.M. (Washington State Univ., Pullman (USA))


    The conversion of geranyl pyrophosphate to (+)-bornyl pyrophosphate and (+)-camphene is considered to proceed by the initial isomerization of the substrate to (-)-(3R)-linalyl pyrophosphate and the subsequent cyclization of this bound intermediate. In the case of (-)-bornyl pyrophosphate and (-)-camphene, isomerization of the substrate to the (+)-(3S)-linalyl intermediate precedes cyclization. The geranyl and linalyl precursors were shown to be mutually competitive substrates (inhibitors) of the relevant cyclization enzymes isolated from Salvia officinalis (sage) and Tanacetum vulgare (tansy) by the mixed substrate analysis method, demonstrating that isomerization and cyclization take place at the same active site. Incubation of partially purified enzyme preparations with (3R)-(1Z-3H)linalyl pyrophosphate plus (1-14C)geranyl pyrophosphate gave rise to double-labeled (+)-bornyl pyrophosphate and (+)-camphene, whereas incubation of enzyme preparations catalyzing the antipodal cyclizations with (3S)-(1Z-3H)-linalyl pyrophosphate plus (1-14C)geranyl pyrophosphate yielded double-labeled (-)-bornyl pyrophosphate and (-)-camphene. Each product was then transformed to the corresponding (+)- or (-)-camphor without change in the 3H:14C isotope ratio, and the location of the tritium label was deduced in each case by stereoselective, base-catalyzed exchange of the exo-alpha-hydrogen of the derived ketone. The finding that the 1Z-3H of the linalyl precursor was positioned at the endo-alpha-hydrogen of the corresponding camphor in all cases, coupled to the previously demonstrated retention of configuration at C1 of the geranyl substrate in these transformations, confirmed the syn-isomerization of geranyl pyrophosphate to linalyl pyrophosphate and the cyclization of the latter via the anti,endo- conformer.

  4. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: Catalytic promiscuity and cyclization of farnesyl pyrophosphate geometrical isomers (United States)

    Lopez-Gallego, Fernando; Agger, Sean A.; Pella, Daniel A.; Distefano, Mark D.; Schmidt-Dannert, Claudia


    Sesquiterpene synthases catalyze with different catalytic fidelity the cyclization of farnesyl pyrophosphate (FPP) into hundreds of known compounds with diverse structures and stereochemistries. Two sesquiterpene synthases, Cop4 and Cop6, were previously isolated from Coprinus cinereus as part of a fungal genome survey. This study investigates the reaction mechanism and catalytic fidelity of the two enzymes. Cyclization of all-trans-FPP ((E,E)-FPP) was compared to the cyclization of the cis-trans isomer of FPP ((Z,E)-FPP) as a surrogate for the secondary cisoid neryl cation intermediate generated by sesquiterpene synthases capable of isomerizing the C2-C3 π bond of all-trans-FPP. Cop6 is a “high-fidelity” α-cuprenene synthase that retains its fidelity under various conditions tested. Cop4 is a catalytically promiscuous enzyme that cyclizes (E,E)-FPP into multiple products, including (−)-germacrene D and cubebol. Changing the pH of the reaction drastically alters the fidelity of Cop4 and makes it a highly selective enzyme. Cyclization of (Z,E)-FPP by Cop4 and Cop6 yields products that are very different from those obtained with (E,E)-FPP. Conversion of (E,E)-FPP proceeds via a (6R)-β-bisabolyl carbocation in the case of Cop6 and an (E,E)-germacradienyl carbocation in the case of Cop4. However, (Z,E)-FPP is cyclized via a (6S)-β-bisabolene carbocation by both enzymes. Structural modeling suggests that differences in the active site and the loop that covers the active site of the two enzymes may explain their different catalytic fidelities. PMID:20419721

  5. Synthesis of polyhydroxylated pyrrolidines from sugar-derived bromonitriles through a cascade addition of allylmagnesium bromide/cyclization/reduction. (United States)

    Malik, Michał; Jarosz, Sławomir


    The synthesis of polyhydroxylated 2-allylpyrrolidines from sugar-derived bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/reduction with Zn(BH4)2 is described. The stereochemical course of the reduction step is rationalized. Two of the obtained compounds are transformed into stereoisomers of naturally-occurring iminosugar (+)-lentiginosine. In an alternative approach, 2,2-diallylpyrrolidines are obtained from bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/addition of another equivalent of allylmagnesium bromide.

  6. Highly stereoselective construction of spiro[4.5]decanes by SmI(2)-promoted ketyl radical mediated tandem cyclization. (United States)

    Inui, Masaharu; Nakazaki, Atsuo; Kobayashi, Susumu


    [reaction: see text] Ketyl radical mediated tandem cyclization of omega-alkynyl carbonyl compounds bearing activated alkene using SmI(2) gave spiro[4.5]decanes stereoselectively. In the presence of HMPA, alpha,beta-unsaturated esters and alkenyl phosphonates were converted to spiro[4.5]decanes and a monocyclic compound, respectively. In the presence of Sm, bicyclic lactones were obtained from alpha,beta-unsaturated esters. The spiro[4.5]decane was provided from an alkenyl phosphonate. Interestingly, the stereochemical changeover at the first cyclization has been controlled by means of a variety of activators.

  7. Substitution controlled functionalization of ortho-bromobenzylic alcohols via palladium catalysis: synthesis of chromenes and indenols. (United States)

    Mahendar, Lodi; Satyanarayana, Gedu


    An efficient domino Pd-catalyzed transformation of simple ortho-bromobenzyl tertiary alcohols to chromenes is presented. Their formation is believed to proceed via the formation of a five-membered palladacycle, which, in turn, involves in an intermolecular homocoupling with the second ortho-bromobenzyltertiary alcohol to yield the homo-biaryl bond followed by intramolecular C-O bond formation. Interestingly, when there is an allylic substituent on the benzylic carbon atom, a chemoselective switch was observed, which preferred intramolecular Heck coupling and gave indenols. Further, it has been confirmed that the tertiary alcohol functionality is indispensible to give the coupled products, whereas the use of primary/secondary benzylic alcohols furnished the simple carbonyl products via a possible reductive debromination followed by oxidation due to the availability of β-hydrogen(s).

  8. Chemical Kinetics of Hydrogen Atom Abstraction from Allylic Sites by (3)O2; Implications for Combustion Modeling and Simulation. (United States)

    Zhou, Chong-Wen; Simmie, John M; Somers, Kieran P; Goldsmith, C Franklin; Curran, Henry J


    Hydrogen atom abstraction from allylic C-H bonds by molecular oxygen plays a very important role in determining the reactivity of fuel molecules having allylic hydrogen atoms. Rate constants for hydrogen atom abstraction by molecular oxygen from molecules with allylic sites have been calculated. A series of molecules with primary, secondary, tertiary, and super secondary allylic hydrogen atoms of alkene, furan, and alkylbenzene families are taken into consideration. Those molecules include propene, 2-butene, isobutene, 2-methylfuran, and toluene containing the primary allylic hydrogen atom; 1-butene, 1-pentene, 2-ethylfuran, ethylbenzene, and n-propylbenzene containing the secondary allylic hydrogen atom; 3-methyl-1-butene, 2-isopropylfuran, and isopropylbenzene containing tertiary allylic hydrogen atom; and 1-4-pentadiene containing super allylic secondary hydrogen atoms. The M06-2X/6-311++G(d,p) level of theory was used to optimize the geometries of all of the reactants, transition states, products and also the hinder rotation treatments for lower frequency modes. The G4 level of theory was used to calculate the electronic single point energies for those species to determine the 0 K barriers to reaction. Conventional transition state theory with Eckart tunnelling corrections was used to calculate the rate constants. The comparison between our calculated rate constants with the available experimental results from the literature shows good agreement for the reactions of propene and isobutene with molecular oxygen. The rate constant for toluene with O2 is about an order magnitude slower than that experimentally derived from a comprehensive model proposed by Oehlschlaeger and coauthors. The results clearly indicate the need for a more detailed investigation of the combustion kinetics of toluene oxidation and its key pyrolysis and oxidation intermediates. Despite this, our computed barriers and rate constants retain an important internal consistency. Rate constants

  9. Genome wide association mapping in Arabidopsis thaliana identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense

    Directory of Open Access Journals (Sweden)

    Marta Francisco


    Full Text Available A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL, may provide direct feedback regulation, linking defense metabolism outputs to the growth and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 µM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

  10. Resonance energies of the allyl cation and allyl anion: contribution by resonance and inductive effects toward the acidity and hydride abstraction enthalpy of propene. (United States)

    Barbour, Josiah B; Karty, Joel M


    Density functional theory was employed to calculate the acidities and hydride abstraction enthalpies of propene (3) and propane (4), along with their vinylogues (5 and 6, respectively). The same reaction enthalpies were calculated for the propene vinylogues in which the terminal vinyl group was rotated perpendicular to the rest of the conjugated system (7). The contribution by resonance and inductive effects toward the acidity and hydride abstraction enthalpy of each vinylogue of 5 (n = 1-3) was computed and extrapolated to n = 0 (the parent propene system). The resonance energies of the allyl cation and anion were determined to be about 20-22 and 17-18 kcal/mol, respectively. Comparisons are made to resonance energies calculated using other methodologies.

  11. Palladium-catalyzed aryl amination-heck cyclization cascade: A one-flask approach to 3-substituted Indoles

    DEFF Research Database (Denmark)

    Jensen, Thomas; Pedersen, Henrik; Bang-Andersen, B.;


    Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation of a sin...

  12. Stereoselective Synthesis of (Z)-α-Alkylidene-γ-Butyrolactones via Pd-Catalyzed CO Insertion and Cyclization

    Institute of Scientific and Technical Information of China (English)

    Lijun Liu; Fentair Luo


    Four new (Z)-2-phenoxymethylene-4-pentanolide derivatives and four (Z)-2-phenoxymethyl-2penten-γ-lactone derivatives were prepared via Pd-catalyzed carbon monoxide insertion and intramolecular cyclization. All compounds were characterized by IR, iH NMR, 13C NMR, MS spectra and elemental analysis. The plausible mechanism of the reaction was discussed.

  13. Synthetic scope, computational chemistry and mechanism of a base induced 5-endo cyclization of benzyl alkynyl sulfides (United States)

    Motto, John M.; Castillo, Álvaro; Montemayer, Laura K.; Sheepwash, Erin E.


    We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the aromatic ring. Evidence indicates there is rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization. Theoretical calculations were also conducted to help rationalize the base induced 5-endo cyclization of benzyl 1-propynyl sulfide (1a). The potential energy surface was calculated for the formation of 2,3-dihydrothiophene in a reaction of benzyl 1-propynyl sulfide (1a) with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p) in acetonitrile with the CPCM solvent model. It is significant that the benzyl propa-1,2-dien-1-yl sulfane (6) possessed a lower benzylic proton affinity than the benzyl prop-2-yn-1-yl sulfane (8) thus favoring the base induced reaction of the former. From benzyl(propa-1,2-dien-1-yl sulfane (6), 2,3-dihydrothiophene can be formed via a conjugate base that undergoes 5-endo-trig cyclization followed by a protonation step. PMID:21442022

  14. Importance of cytochromes in cyclization reactions: quantum chemical study on a model reaction of proguanil to cycloguanil. (United States)

    Arfeen, Minhajul; Patel, Dhilon S; Abbat, Sheenu; Taxak, Nikhil; Bharatam, Prasad V


    Proguanil, an anti-malarial prodrug, undergoes cytochrome P450 catalyzed biotransformation to the pharmacologically active triazine metabolite (cycloguanil), which inhibits plasmodial dihydrofolate reductase. This cyclization is catalyzed by CYP2C19 and many anti-malarial lead compounds are being designed and synthesized to exploit this pathway. Quantum chemical calculations were performed using the model species (Cpd I for active species of cytochrome and N4-isopropyl-N6-methylbiguanide for proguanil) to elucidate the mechanism of the cyclization pathway. The overall reaction involves the loss of a water molecule, and is exothermic by approximately 55 kcal/mol, and involves a barrier of approximately 17 kcal/mol. The plausible reaction pathway involves the initial H-radical abstraction from the isopropyl group by Cpd I, followed by two alternative paths- (i) oxygen rebound to provide hydroxyl derivative and (ii) loss of additional H-radical to yield 1,3,5-triazatriene, which undergoes cyclization. This study helped in understanding the role of the active species of cytochromes in this important cyclization reaction.

  15. Synthesis of Heterocycles through a Ruthenium‐Catalyzed Tandem Ring‐Closing Metathesis/Isomerization/N‐Acyliminium Cyclization Sequence

    DEFF Research Database (Denmark)

    Ascic, Erhad; Jensen, Jakob Feldthusen; Nielsen, Thomas Eiland


    Tandem bicycle: In the title reaction double bonds created during ring-closing metathesis isomerize to generate reactive iminium intermediates that undergo intramolecular cyclization reactions with tethered heteroatom and carbon nucleophiles. In this way, a series of biologically interesting hete...... heterocyclic compounds can be made, including a known precursor for the total synthesis of the antiparasitic natural product harmicine....

  16. Ascorbic Acid-Initiated Tandem Radical Cyclization of N-Arylacrylamides to Give 3,3-Disubstituted Oxindoles

    Directory of Open Access Journals (Sweden)

    Sheng Liu


    Full Text Available An ascorbic acid-promoted and metal-free tandem room temperature cyclization of N-arylacrylamides with 4-nitrobenzenediazonium generated in situ was developed. This reaction proceeds smoothly through a radical mechanism and provides an environmentally friendly alternative approach to biologically active 3-alkyl-3-benzyloxindoles, avoiding the use of excess oxidants and light irradiation.

  17. Enantioselective Nickel-Catalyzed anti-Carbometallative Cyclizations of Alkynyl Electrophiles Enabled by Reversible Alkenylnickel E/Z Isomerization (United States)


    Nickel-catalyzed additions of arylboronic acids to alkynes, followed by enantioselective cyclizations of the alkenylnickel species onto tethered ketones or enones, are reported. These reactions are reliant upon the formal anti-carbonickelation of the alkyne, which is postulated to occur by the reversible E/Z isomerization of an alkenylnickel species. PMID:27333360

  18. Synthesis of Imidazo pyridines and Pyridopyrimidines in Water and their S{sub N}Ar Cyclizations

    Energy Technology Data Exchange (ETDEWEB)

    Chanu, Langpoklakpam Gellina; Singh, Thokchom Prasanta; Singh, Okram Mukherjee [Manipur Univ., Manipur (India); Jang, Yong Ju; Yoon, Yongjin; Singh, Okram Mukherjee; Lee, Sanggyeong [Gyeongsang National Univ., Jinju (Korea, Republic of)


    Synthesis of tetrahydroimidazo pyridines and tetrahydropyrido pyrimidines by a one-pot and three component reaction of α-oxoketenedithioacetals, diamines and DMAD in water has been described. Different routes for accessing the desired compounds were examined and a few specially designed-substrates have been utilized further to afford the new imidazo and pyrido fused naphthyridine tetracyclic compound by SNAr intramolecular cyclization.

  19. An Intramolecular Heck reaction that Prefers a 5-endo- to a 6-exo-trig Cyclization Pathway

    DEFF Research Database (Denmark)

    Vital, Paulo; Norrby, Per-Ola; Tanner, David Ackland


    A regioselective aromatic Claisen rearrangement was used to prepare 17a, the precursor of triflate 17e. The intramolecular Heck reaction of 17e is promoted only by bidentate phosphine ligands, giving exclusively and in excellent yield 20, the product of a 5-endo-trig cyclization, despite the poss...

  20. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism. (United States)

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji


    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism.

  1. Thermosetting composite matrix materials based on allyl and/or propargyl substituted cyclopentadiene, indene and fluorene (United States)

    Tregre, Gregory Jude

    A series of all-hydrocarbon thermoset composite matrix resins was synthesized via electrophilic substitution of cyclopentadiene, indene, and fluorene ring systems with allyl and/or propargyl halides under phase transfer conditions. Reaction of cyclopentadiene with allyl chloride (ACP resin), propargyl bromide (PCP resin) or various feed ratios of allyl chloride and propargyl bromide (APCP resins) yielded mixtures of products with 2-6 substituents per cyclopentadiene ring. Reaction of indene with allyl chloride (Al resins) or propargyl bromide (PI resins) yielded mixtures of products with 2-4 substituents per indene. In both sets of resins the allyl functionality obtained a greater average degree of substitution than the analogous propargyl species. Differential scanning calorimetric (DSC) analysis of the multifunctional resins showed broad, high-energy thermal cures in all cases. The enthalpies of cure for ACP and PCP were 750 J/g and 805 J/g, respectively, with peak cure energies occurring at 310 and 248sp°C. The enthalpy of cure for APCP resins ranged from 750 J/g to 800 J/g with higher propargyl-functional resins yielding higher enthalpies of cure. Physically mixed ACP/PCP resin systems gave peak cure temperatures and energy values comparable to APCP resins. The enthalpies of cure for Al and PI-resins were 480 J/g and 630 J/g, respectively. Peak cure temperature for Al resin was 320sp°C, while the peak cure for PI resin occurred at 282sp°C. Infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) were used to evaluate mechanisms of cure in the experimental resins. The allyl functional resins cured through a combination of ene reactions and polyaddition reactions. The propargyl functional resins cured through ene reactions and polyadditions but also underwent some cyclotrimerization of the propargyl functionalities. A small amount of autoxidation was seen in all of the resins. Thermal stability and carbon yields of the cured resins were

  2. Synthesis of fused azole-piperidionoses: A free radical cyclization approach

    Energy Technology Data Exchange (ETDEWEB)

    Marco-Contelles, Jose; Alhambra Jimenez, Carolina [Instituto de Quimica Organica General (CSIC), Madrid (Spain)


    A new strategy has been reported for the synthesis of fused azole-piperidinoses featuring and unprecedented and very efficient 6-exo-trig free radical cyclization onto heterocyclic sugar templates. These compounds are key intermediates for the synthesis of known or analogues of azole-glycosidase inhibitors. In this communication we describe our recent and successful results on the synthesis of fused triazole-piperidinoses. Radical precursors have been prepared by standard methodologies from 1, 2:5, 6-bis-O-isopropylidene-{alpha}-D-glucofuranose (4) via triazoles linked at C3 with {beta}-orientation, readily obtained by 1, 3-dipolar cycloaddition of azide 5 with diethyl acetylenedicarboxylate or methyl propiolate, and by S{sub N}2 displacement of the tosylate at C3 with 1, 2, 4-triazole in compound 20. The key 6-exp-trig free radical cyclizations proceeded in the usual conditions [tributyltin hydride or tris(trimethylsily)silane, AIBN, toluene] yielding the azaannulated sugars 9, 11, 19 and 23 in good or excellent yields. A mechanism for these cyclizations has been proposed. [Spanish] Se ha informado una nueva estrategia para la sintesis azol-piperidinosas fusionadas mediante una ciclizacion 6-exo-trig muy eficiente y sin precedentes, sobre plantillas de azucares heterociclicos. Estos compuestos son intermediarios claves para la sintesis de inhibidores de azol-glicosidasa conocidos analogos de ellos. En esta comunicacion describimos nuestros resultados recientes y exitosos sobre la sintesis de triazol-piperidinosas. Los precursores de radicales fueron preparados por la metodologia usual a partir de 1, 2:5, 6-bis-O-isopropiliden-{alpha}-D-glucofuranosa (4) via triazoles unidos en C3, con orientacion {beta}, los cuales se obtienen facilmente por cicloadicion 1, 3-dipolar de la azida 5 con acetilendicarboxilato de dietilo o propiolato de metilo y por desplazamiento S{sub N}2 del tosilato en C3 con 1, 2, 4-triazol en el compuesto 20. Las ciclizaciones 6-exo

  3. Direct catalytic asymmetric addition of allyl cyanide to ketones via soft Lewis acid/hard Brønsted base/hard Lewis base catalysis. (United States)

    Yazaki, Ryo; Kumagai, Naoya; Shibasaki, Masakatsu


    We report that a hard Lewis base substantially affects the reaction efficiency of direct catalytic asymmetric gamma-addition of allyl cyanide (1a) to ketones promoted by a soft Lewis acid/hard Brønsted base catalyst. Mechanistic studies have revealed that Cu/(R,R)-Ph-BPE and Li(OC(6)H(4)-p-OMe) serve as a soft Lewis acid and a hard Brønsted base, respectively, allowing for deprotonative activation of 1a as the rate-determining step. A ternary catalytic system comprising a soft Lewis acid/hard Brønsted base and an additional hard Lewis base, in which the basicity of the hard Brønsted base Li(OC(6)H(4)-p-OMe) was enhanced by phosphine oxide (the hard Lewis base) through a hard-hard interaction, outperformed the previously developed binary soft Lewis acid/hard Brønsted base catalytic system, leading to higher yields and enantioselectivities while using one-tenth the catalyst loading and one-fifth the amount of 1a. This second-generation catalyst allows efficient access to highly enantioenriched tertiary alcohols under nearly ideal atom-economical conditions (0.5-1 mol % catalyst loading and a substrate molar ratio of 1:2).

  4. Direct asymmetric allylic alkenylation of N-itaconimides with Morita-Baylis-Hillman carbonates

    KAUST Repository

    Yang, Wenguo


    The asymmetric allylic alkenylation of Morita-Baylis-Hillman (MBH) carbonates with N-itaconimides as nucleophiles has been developed using a commercially available Cinchona alkaloid catalyst. A variety of multifunctional chiral α-methylene-β-maleimide esters were attained in moderate to excellent yields (up to 99%) and good to excellent enantioselectivities (up to 91% ee). The origin of the regio- and stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed regio- and enantioselectivity. © 2012 American Chemical Society.

  5. Lanthanum triflate triggered synthesis of tetrahydroquinazolinone derivatives of N-allyl quinolone and their biological assessment

    Directory of Open Access Journals (Sweden)

    Jardosh Hardik H.


    Full Text Available A series of 24 derivatives of tetrahydroquinazolinone has been synthesized by one-pot cyclocondensation reaction of N-allyl quinolones, cyclic β-diketones and (thiourea/N-phenylthiourea in presence of lanthanum triflate catalyst. This methodology allowed us to achieve the products in excellent yield by stirring at room temperature. All the synthesized compounds were investigated against a representative panel of pathogenic strains using broth microdilution MIC (minimum inhibitory concentration method for their in vitro antimicrobial activity. Amongst these sets of heterocyclic compounds 5h, 6b, 6h, 5f, 5l, 5n and 6g found to have admirable activity.

  6. N-(2-Allyl-4-ethoxy-2H-indazol-5-yl-4-methylbenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Hakima Chicha


    Full Text Available The indazole ring system of the title compound, C19H21N3O3S, is almost planar (r.m.s. deviation = 0.0192 Å and forms dihedral angles of 77.99 (15 and 83.9 (3° with the benzene ring and allyl group, respectively. In the crystal, centrosymmetrically related molecules are connected by pairs of N—H...O hydrogen bonds into dimers, which are further linked by C—H...O hydrogen bonds, forming columns parallel to the b axis.

  7. Thermophysical properties and reaction kinetics of γ-irradiated poly allyl diglycol carbonates nuclear track detector (United States)

    Elmaghraby, Elsayed K.; Seddik, Usama


    Kinetic thermogravimetric technique was used to study the effect of gamma irradiation on the poly allyl diglycol carbonates (PADC) within the dose range from 50 to ? Gy. The approach of Coats-Redfern was used to analyze the data. Results showed that low doses around 50 Gy make the polymer slightly more resistive to heat treatment. Higher radiation doses cause severe effects in the samples accompanied by the formation of lower molecular mass species and consequent crosslinking. Results support the domination of re-polymerization and crosslinking for the γ radiation interaction PADC at dose below about ? Gy, while the situation is inverted above ? Gy in which chain secession dominates.

  8. Synthesis of Aminophosphine Ligands with Binaphthyl Backbones for Silver(I)-catalyzed Enantioselective Allylation of Benzaldehyde

    Institute of Scientific and Technical Information of China (English)

    WANG,Yi(王以); JI,Bao-Ming(吉保明); DING,Kui-Ling(丁奎岭)


    A series of aminophosphine ligands was synthesized from 2amino-2′-hydroxy-1,1′-binaphthyl (NOBIN). Their asymmetric induction efficiency was examined for silver(I)catalyzed enantioselective allylation reaction of benzaldehyde with allyltributyltin.Under the optimized reaction conditions,quantitative yield as well as moderate ee value (54.5% ee)of product was achieved by the catalysis with silver(I)/3 complex. The effects of the binaphthyl backbone and the substituted situated at chelating N, Patoms on enantioselectivity of the reaction were also discussed.

  9. Synthesis of Aryl Allyl Ether in the Recyclable Ionic Liquid [bmim]PF6

    Institute of Scientific and Technical Information of China (English)

    Zhou Mei-Yun; Li Yi-Qun; Xu Xin-Ming


    Ionic liquids, especially imidazonium salts, have recently gained recognition as possible environmentally benign alternative chemical process solvents. This is mainly due to their nonvolatile nature, insolubility in some solvents as well as their ability to dissolve a wide range of organic and inorganic materials, allowing the ionic liquids easy recovery and recycling. Examples of their application in organic reactions have been summarized in a number of recent review articles.1Aryl allyl ether is very useful intermediate in organic synthesis. The Williamson reaction is a well knows method for the preparation ethers. However, the reaction of alkylating agents with the phenoxide ions was conventionally carried out in the organic solvents. The usual solvents for this type of reaction are DCM, 2 DMSO, 3 DMF, 4 CH3CN5 etc. With the current desire to avoid the use of organic molecular solvents in organic synthesis, we decide to investigate the use of the ionic liquid for the alternative solvent for the Williamson reaction to prepare the aryl allyl ethers. The ionic liquid employed here was the moisture stable 1-butyl-3-methylimidazolium hexafluorophosphate [bmim]PF6.6 The ionic liquid is non-volatile, thermally stable, and depending on the anion, can present low immiscible with water,alkanes and dialky ethers. We have now found that aryl allyl ethers can have been obtained from various phenols and allyl bromide in the presence of potassium hydroxide in [bmim]PF6 as a replacement for classical organic solvents in the ambient temperature. The results are shown in Scheme 1.The reaction were carried out by simple mixing the phenolwith the ally bromide and potassium hydroxide in [bmim]PF6 and stirred at room temperature for 4h. The results are summarized in Table 1.In conclusion, Williamson reaction can be successfully conducted in ionic liquid [bmim]PF6 with a number of advantages: the procedure is simple, the reaction condition is mild and the yields are excellent

  10. Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups (United States)

    Meng, Fanke; Li, Xiben; Torker, Sebastian; Shi, Ying; Shen, Xiao; Hoveyda, Amir H.


    Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates. Nonetheless, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown. Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable because the resulting products could then be subjected to further modifications. However, such reactions, especially when dienoates contain two equally substituted olefins, are scarce and are confined to reactions promoted by a phosphine-copper catalyst (with an alkyl Grignard reagent, dialkylzinc or trialkylaluminium compounds), a diene-iridium catalyst (with arylboroxines), or a bisphosphine-cobalt catalyst (with monosilyl-acetylenes). 1,6-Conjugate additions are otherwise limited to substrates where there is full substitution at the C4 position. It is unclear why certain catalysts favour bond formation at C6, and—although there are a small number of catalytic enantioselective conjugate allyl additions—related 1,6-additions and processes involving a propargyl unit are non-existent. Here we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenyl-boron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 per cent yield, >98:2 diastereomeric ratio (for allyl additions) and 99:1 enantiomeric ratio. We elucidate the mechanistic details, including the origins of high site selectivity (1,6- versus 1,4-) and enantioselectivity as a function of the catalyst

  11. N-(1-Allyl-3-chloro-4-ethoxy-1H-indazol-5-yl-4-methylbenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Hakima Chicha


    Full Text Available In the title compound, C19H20ClN3O3S, the benzene ring is inclined to the indazole ring system by 51.23 (8°. In the crystal, molecules are linked by pairs of N—H...O hydrogen bonds, forming inversion dimers which stack in columns parallel to [011]. The atoms in the allyl group are disordered over two sets of sites with an occupancy ratio of 0.624 (8:0.376 (8.

  12. Alcohol and Hepatitis (United States)

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one of the ...

  13. Alcohol and Hepatitis (United States)

    ... code here Enter ZIP code here Daily Living: Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one ... related to choices you make about your lifestyle . Alcohol and fibrosis Fibrosis is the medical term for ...

  14. Backbone cyclization of a recombinant cystine-knot peptide by engineered Sortase A. (United States)

    Stanger, Karen; Maurer, Till; Kaluarachchi, Harini; Coons, Mary; Franke, Yvonne; Hannoush, Rami N


    Cyclotides belong to the family of cyclic cystine-knot peptides and have shown promise as scaffolds for protein engineering and pharmacological modulation of cellular protein activity. Cyclotides are characterized by a cystine-knotted topology and a head-to-tail cyclic polypeptide backbone. While they are primarily produced in plants, cyclotides have also been obtained by chemical synthesis. However, there is still a need for methods to generate cyclotides in high yields to near homogeneity. Here, we report a biomimetic approach which utilizes an engineered version of the enzyme Sortase A to catalyze amide backbone cyclization of the recombinant cyclotide MCoTI-II, thereby allowing the efficient production of active homogenous species in high yields. Our results provide proof of concept for using engineered Sortase A to produce cyclic MCoTI-II and should be generally applicable to generating other cyclic cystine-knot peptides.

  15. Palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to a library of tetraphenylenes (United States)

    Zhu, Chendan; Zhao, Yue; Wang, Di; Sun, Wei-Yin; Shi, Zhuangzhi


    Aryl–aryl bond formation constitutes one of the most important subjects in organic synthesis. The recent developments in direct arylation reactions forming aryl–aryl bond have emerged as very attractive alternatives to traditional cross-coupling reactions. Here, we describe a general palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to build a library of tetraphenylenes. This transformation represents one of the very few examples of C-H activation process that involves simultaneous formation of two aryl–aryl bonds. Oxygen plays a vital role by ensuring high reactivity, with air as the promoter furnished the best results. We anticipate this ligand-free and aerobic catalytic system will simplify the synthesis of tetraphenylenes as many of the reported methods involve use of preformed organometallic reagents and will lead to the discovery of highly efficient new direct arylation process.

  16. Cyclization of 1,4-hydroxycarbonyls is not a homogenous gas phase process (United States)

    Dibble, Theodore S.


    Previous studies of 1,4-hydroxycarbonyls derived from alkanes have suggested that they can cyclize to saturated furans, which can subsequently eliminate water to form the corresponding dihydrofurans. CBS-QB3 and G3 studies of 5-hydroxy-2-pentanone and 2-hydroxypentanal show that both steps have activation barriers far too large for these reactions to occur as homogenous gas phase reactions. Similar results were obtained in CBS-QB3 studies of the analogous process leading from 2- and 3-methyl-4-hydroxy-2-butenal (species posited to form in the degradation of isoprene) to 3-methylfuran. The latter two processes are much more favorable, thermodynamically, than the formation of dihydrofurans from the saturated 1,4-hydroxycarbonyls.

  17. A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families. (United States)

    De Moliner, Fabio; Hulme, Christopher


    A concise synthesis of two pharmacologically relevant classes of molecules possessing the imidazoquinoxaline core is reported. The protocol involves use of 1,2-phenylenediamines and glyoxylic acid derivatives, namely ethyl glyoxylate or benzylglyoxamide, along with tosylmethylisocyanides in a microwave-assisted Van Leusen three-component condensation. Subsequent unmasking (Boc removal) of an internal amino-nucleophile promotes deprotection and cyclization that take place either spontaneously in a one-pot fashion to give 8 or upon acidic treatment under microwave irradiation after isolation of the imidazole intermediate to give 11. Of note, a tricyclic framework is hence assembled by means of a rapid and straightforward method with a high bond-forming efficiency.

  18. Spectral assignments and structural studies of a warfarin derivative stereoselectively formed by tandem cyclization (United States)

    Velayutham Pillai, M.; Rajeswari, K.; Vidhyasagar, T.


    The structural elucidation of a Mannich condensation product of rac-Warfarin with benzaldehyde and methyl amine was carried out using IR, Mass, 1H NMR, 13C NMR, 1H-1H COSY, 1H-13C COSY, DEPT-135, HMBC, NOESY spectra and single crystal X-ray diffraction. Formation of a new pyran ring via a tandem cyclization in the presence of methyl amine was observed. The optimized geometry and HOMO-LUMO energy gap along with other important physical parameters were found by Gaussian 09 program using HF 6-31G (d, p) and B3YLP/DFT 6-31G (d, p) level of theory. The preferred conformation of the piperidine ring in solution state was found to be chair from the NMR spectra. Single crystal X-ray diffraction and optimized geometry (by theoretical study) also confirms the chair conformation in the solid state.

  19. A Double Activation Method for the Conversion of Vinyl Epoxides into vic-Amino Alcohols and Chiral Benzoxazine/Quinoxaline Derivatives. (United States)

    Srikanth, Gourishetty; Ramakrishna, Kallaganti V S; Sharma, Gangavaram V M


    A new method for the synthesis of 1,2-syn-vic amino alcohols (with double inversion of configuration) from vinyl epoxides, by the amination of a π-allyl palladium-borate complex generated by using Pd(0) and phenyl-o-phenylene borate (a double activation technique), is reported. Further, this new method with broad functional group compatibility was extended to a one-pot/two-step synthesis of chiral benzoxazine and quinoxaline derivatives.

  20. Titanocene(III)-catalyzed 6-exo versus 7-endo cyclizations of epoxypolyprenes: efficient control and synthesis of versatile terpenic building blocks. (United States)

    Justicia, José; Jiménez, Tania; Miguel, Delia; Contreras-Montoya, Rafael; Chahboun, Rachid; Alvarez-Manzaneda, Enrique; Collado-Sanz, Daniel; Cárdenas, Diego J; Cuerva, Juan M


    In this article, a complete study on the selectivity of titanocene(III) cyclization of epoxypolyprenes is presented. The requirements for the formation of six- or seven-membered rings during these cyclizations are determined, taking into account the different substitution pattern in the epoxypolyprene precursor. Thus, a complete selectivity to 6-exo or 7-endo cyclization process has been achieved, yielding mono-, bi-, and even tricyclic compounds, constituting a new and efficient access to this type of derivative. Additionally, this procedure opens the possibility to prepare excellent building blocks for the synthesis of polycyclic compounds with a trisubstituted oxygenated function, which is present in several natural terpenes.

  1. Role of allyl group in the hydroxyl and peroxyl radical scavenging activity of S-allylcysteine. (United States)

    Maldonado, Perla D; Alvarez-Idaboy, J Raúl; Aguilar-González, Adriana; Lira-Rocha, Alfonso; Jung-Cook, Helgi; Medina-Campos, Omar Noel; Pedraza-Chaverrí, José; Galano, Annia


    S-Allylcysteine (SAC) is the most abundant compound in aged garlic extracts, and its antioxidant properties have been demonstrated. It is known that SAC is able to scavenge different reactive species including hydroxyl radical (•OH), although its potential ability to scavenge peroxyl radical (ROO•) has not been explored. In this work the ability of SAC to scavenge ROO• was evaluated, as well as the role of the allyl group (-S-CH(2)-CH═CH(2)) in its free radical scavenging activity. Two derived compounds of SAC were prepared: S-benzylcysteine (SBC) and S-propylcysteine (SPC). Their abilities to scavenge •OH and ROO• were measured. A computational analysis was performed to elucidate the mechanism by which these compounds scavenge •OH and ROO•. SAC was able to scavenge •OH and ROO•, in a concentration-dependent way. Such activity was significantly ameliorated when the allyl group was replaced by benzyl or propyl groups. It was shown for the first time that SAC is able to scavenge ROO•.

  2. Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo (United States)

    Shakoori, Alireza; Bremner, John B; Abdel-Hamid, Mohammed K; Willis, Anthony C; Haritakun, Rachada


    Summary Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. PMID:25977722

  3. Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

    Directory of Open Access Journals (Sweden)

    Alireza Shakoori


    Full Text Available Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol-3-one (65% and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72% heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H-dione heterocyclic system.

  4. Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

    Directory of Open Access Journals (Sweden)

    David Porter


    Full Text Available Iron(II complexes of the tetradentate amines tris(2-pyridylmethylamine (TPA and N,N′-bis(2-pyridylmethyl-N,N′-dimethylethane-1,2-diamine (BPMEN are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with either FeTPA (1 mol % or FeBPMEN (10 mol % converts cyclohexene to the allylic hydroxylamine (tert-butyl cyclohex-2-en-1-yl(hydroxycarbamate in moderate yields. Spectroscopic studies and trapping experiments suggest the reaction proceeds via a nitroso–ene mechanism, with involvement of a free N-Boc-nitroso intermediate. Asymmetric induction is not observed using the chiral tetramine ligand (+-(2R,2′R-1,1′-bis(2-pyridylmethyl-2,2′-bipyrrolidine ((R,R′-PDP.

  5. Mechanism of the cobalt oxazoline palladacycle (COP)-catalyzed asymmetric synthesis of allylic esters. (United States)

    Cannon, Jeffrey S; Kirsch, Stefan F; Overman, Larry E; Sneddon, Helen F


    The catalytic enantioselective S(N)2' displacement of (Z)-allylic trichloroacetimidates catalyzed by the palladium(II) complex [COP-OAc](2) is a broadly useful method for the asymmetric synthesis of chiral branched allylic esters. A variety of experiments aimed at elucidating the nature of the catalytic mechanism and its rate- and enantiodetermining steps are reported. Key findings include the following: (a) the demonstration that a variety of bridged-dipalladium complexes are present and constitute resting states of the COP catalyst (however, monomeric palladium(II) complexes are likely involved in the catalytic cycle); (b) labeling experiments establishing that the reaction proceeds in an overall antarafacial fashion; (c) secondary deuterium kinetic isotope effects that suggest substantial rehybridization at both C1 and C3 in the rate-limiting step; and (d) DFT computational studies (B3-LYP/def2-TZVP) that provide evidence for bidentate substrate-bound intermediates and an anti-oxypalladation/syn-deoxypalladation pathway. These results are consistent with a novel mechanism in which chelation of the imidate nitrogen to form a cationic palladium(II) intermediate activates the alkene for attack by external carboxylate in the enantiodetermining step. Computational modeling of the transition-state structure for the acyloxy palladation step provides a model for enantioinduction.

  6. The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

    KAUST Repository

    Ebner, Davidâ C.


    The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 degrees C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.

  7. Efficient Regioselective Synthesis of 3-1odoindole N-Carboximidamides and N-Carboximidoates by a Sequential Aza-Wittig/Iodine Induced Cyclization

    Institute of Scientific and Technical Information of China (English)

    聂熠博; 段专; 丁明武


    3-Iodoindole N-carboximidamides and N-carboximidoates 4 were prepared regioselectively via a sequential aza-Wittig/iodine induced cyclization, starting from easily accessible 2-alkynylphenyl iminophosphorane, isocyanates, various nucleophiles and iodine.

  8. A cyclization-induced emission enhancement (CIEE)-based ratiometric fluorogenic and chromogenic probe for the facile detection of a nerve agent simulant DCP. (United States)

    Mahapatra, Ajit Kumar; Maiti, Kalipada; Manna, Saikat Kumar; Maji, Rajkishor; Mondal, Sanchita; Das Mukhopadhyay, Chitrangada; Sahoo, Prithidipa; Mandal, Debasish


    The first ratiometric fluorescent probe for the detection of a nerve agent simulant was developed based on tandem phosphorylation and intramolecular cyclization, by which high sensitivity as well as large emission shift could be achieved.

  9. Asymmetric allylic alkylation in combination with ring-closing metathesis for the preparation of chiral N-heterocycles

    NARCIS (Netherlands)

    Teichert, Johannes F.; Zhang, Suyan; Zijl, Anthoni W. van; Slaa, Jan Willem; Minnaard, Adriaan J.; Feringa, Bernard


    Asymmetric copper-catalyzed allylic substitution with methylmagnesium bromide is employed in combination with ring-closing olefin metathesis or ene-yne metathesis to achieve the synthesis of chiral, unsaturated nitrogen heterocycles. The resulting six- to eight-membered chiral heterocycles are acces

  10. The NBS Reaction: A Simple Explanation for the Predominance of Allylic Substitution over Olefin Addition by Bromine at Low Concentrations. (United States)

    Wamser, Carl C.; Scott, Lawrence T.


    Examines mechanisms related to use of N-bromosuccinimide (NBS) for bromination at an allylic position. Also presents derived rate laws for three possible reactions of molecular bromine with an alkene: (1) free radical substitution; (2) free radical addition; and (3) electrophilic addition. (JN)

  11. Synthesis of novel chiral phosphine-triazine ligand derived from α-phenylethylamine for Pd-catalyzed asymmetric allylic alkylation

    Institute of Scientific and Technical Information of China (English)

    Jia Di Huang; Xiang Ping Hu; Zhuo Zheng


    A novel chiral phosphine-triazine ligand was synthesized from chiral model reaction of Pd-catalyzed allylic alkylation of rac-l,3-diphenylprop-2-en-l-yl pivalate with dimethyl malonate, good enantioselectivity (90% e.e.) was obtained by using this ligand.

  12. New chiral N, S-ligands with Thiophenyl at Benzylic Position. Palladium(Ⅱ)-catalyzed Enantioselective Allylic Alkylation

    Institute of Scientific and Technical Information of China (English)

    WU,Hao(吴昊); WU,Xun-Wei(巫循伟); HOU,Xue-Long(侯雪龙); DAI,Li-Xin(戴立信); WANG,Quan-Rui(王全瑞)


    New chiral N, S-ligands with oxazoline and thiphenyl substituents at benzene ring and benzylic position have been prepared and applied in palladium-catalyzed asymmetric allylic alkylation reaction to provide the product with high yield and entantioselectivity (82%-93% ee).

  13. Antimicrobial activity of allyl isothiocyanate used to coat biodegradable composite films as affected by storage and handling conditions (United States)

    We evaluated the effects of storage and handling conditions on the antimicrobial activity of biodegradable composite films (polylactic acid and sugar beet pulp) coated with allyl isothiocyanate (AIT). Polylactic acid (PLA) and chitosan were incorporated with AIT and coated on one side of the film. T...

  14. Spectra of carbanions formed from allyl cyanide during isomerization in zeolite NaY-FAU with strong basic sites (United States)

    Hannus, István; Förster, Horst; Tasi, Gyula; Kiricsi, Imre; Molnár, Árpád


    Double bond isomerization of allyl cyanide to crotononitrile over a basic zeolite catalyst was monitored by IR and UV-VIS spectroscopy in order to get information on the surface intermediates involved. Due to the spectral changes the occurence of a carbanionic intermediate seems to be highly probable characterized by an absorption at 400 nm.

  15. Changing the topology of protein backbone: the effect of backbone cyclization on the structure and dynamics of a SH3 domain

    Directory of Open Access Journals (Sweden)

    Frank H Schumann


    Full Text Available Understanding of the effects of the backbone cyclization on the structure and dynamics of a protein is essential for using protein topology engineering to alter protein stability and function. Here we have determined, for the first time, the structure and dynamics of the linear and various circular constructs of the N-SH3 domain from protein c-Crk. These constructs differ in the length and amino acid composition of the cyclization region. The backbone cyclization was carried out using intein-mediated intramolecular chemical ligation between the juxtaposed N- and the C-termini. The structure and backbone dynamics studies were performed using solution NMR. Our data suggest that the backbone cyclization has little effect on the overall three-dimensional structure of the SH3 domain: besides the termini, only minor structural changes were found in the proximity of the cyclization region. In contrast to the structure, backbone dynamics are significantly affected by the cyclization. On the subnanosecond time scale, the backbone of all circular constructs on average appears more rigid than that of the linear SH3 domain; this effect is observed over the entire backbone and is not limited to the cyclization site. The backbone mobility of the circular constructs becomes less restricted with increasing length of the circularization loop. In addition, significant conformational exchange motions (on the sub-millisecond time scale were found in the N-Src loop and in the adjacent β-strands in all circular constructs studied in this work. These effects of backbone cyclization on protein dynamics have potential implications for the stability of the protein fold and for ligand binding.

  16. Stable acetaldehyde--protein adducts as biomarkers of alcohol exposure. (United States)

    Conduah Birt, J E; Shuker, D E; Farmer, P B


    The consumption of alcoholic beverages has been associated with increased risks of a number of chronic disorders including cancers. It is still not clear whether ethyl alcohol or other components such as metabolites are directly involved in the carcinogenic process or whether the effects are due to the modulation of metabolism of other carcinogens. At present, there is no good biomarker of alcohol intake, particularly at low or moderate levels of consumption. A number of studies have shown the ability of the major metabolite acetaldehyde to react with proteins in vitro to give stable and unstable adducts. The interaction of acetaldehyde with model peptides, which correspond to N-terminal globin sequences, was studied. The major stable adduct was identified by mass spectrometry and NMR as a diastereoisomeric mixture of imidazolidinones. This is believed to be formed by reaction and cyclization of the initial Schiff base adduct with the N-terminal valine. Incubation of human globin with acetaldehyde (0-2 mM) yielded products which were identified as the N-terminal adducts by electrospray ionization mass spectrometry (ESI-MS) of proteolytic digests. The specificity and sensitivity of the analysis was improved by the use of on-line HPLC-ESI-MS. Tryptic digests of the modified globin which contained both the N-terminal acetaldehyde adducts of alpha-globin (heptapeptide) and beta-globin (octapeptide) were resolved. These results suggest that analysis of stable imidazolidinone adducts is a promising approach to estimation of alcohol exposure.

  17. Organocatalytic Synthesis of Tetrahydroquinolines from α,β-Unsaturated Ketones via 1,5-Hydride Transfer/Cyclization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Young [Soonchunhyang Univ., Asan (Korea, Republic of)


    We have presented the example of a organo-catalytic enantioselective hydride transfer/cyclization reaction cascade from cyclic amines containing α,β-unsaturated ketones. The synthetically useful ring-fused tetrahydroquinoline derivatives were obtained in moderate to high yields with moderate to high diastereoselectivities. Further investigations for an asymmetric version of this organocatalytic intramolecular redox reaction of α,β-unsaturated ketones are currently underway in our laboratory. The development for direct functionalization of sp{sup 3} C-H bonds has become an area of intense interest in synthetic organic chemistry. Because such reactions offer practical methods for the construction of structurally complex and biologically active organic molecules with atom- and step economy. The 1,5-hydride transfer and subsequent cyclization process is a well-known sp{sup 3} C-H bond function-alization strategy and has attracted considerable interest for its application in the synthesis of heterocyclic compounds.

  18. Efficient Synthesis of Bi-butenolides Derivatives through Oxidative Dimeric Cyclizing-Coupling Reaction of 2,3-Allenoic Acids

    Institute of Scientific and Technical Information of China (English)

    MA Sheng-Ming; YU Zhan-Qian


    @@ Allenes are three carbon functional groups possessing two perpendicular π-orbitals. Their unique reaction be havior is spread over three carbon atoms, which shows great potential in organic synthesis in terms of chirality transfer and diversity, as a result of the axial chirality as well as the substituent-loading capability. Recently, we devoted ourselves to establish a new area of oxidative cyclization-dimerization reactions between two functionalized allenes to give interesting bicyclic compounds in a single step. The formidable challenges are to match the reactivities of two allenes, and regenerate the catalyst, which would be reduced after reductive-elimination. In this paper we wish to disclose our recent studies on the synthesis of bi-butenolides from oxidative cyclization self-coupling reaction of 2,3 allenoic acids, in which a new system (PdCl2/RI/air) for regeneration of the palladium(Ⅱ) species was observed.

  19. Rh(III)-Catalyzed C-H Bond Addition/Amine-Mediated Cyclization of Bis-Michael Acceptors. (United States)

    Potter, Tyler J; Ellman, Jonathan A


    A Rh(III)-catalyzed C-H bond addition/primary amine-promoted cyclization of bis-Michael acceptors is reported. The C-H bond addition step occurs with high chemoselectivity, and the subsequent intramolecular Michael addition, mediated by a primary amine catalyst, sets three contiguous stereocenters with high diastereoselectivity. A broad range of directing groups and both aromatic and alkenyl C-H bonds were shown to be effective in this transformation, affording functionalized piperidines, tetrahydropyrans, and cyclohexanes.

  20. One-pot cascade michael.cyclization reactions of ο-hydroxycinnamaldehydes: Synthesis of functionalized 2,3-dihydrobenzofuranes

    Energy Technology Data Exchange (ETDEWEB)

    Gwon, Sung Hyuk; Kim, Sunggon [Kyonggi Univ., Suwon (Korea, Republic of)


    We described the cascade Michael.cyclization reaction of o-hydroxycinnamaldehydes with diethyl α-bromomalonate promoted by potassium carbonate. The reactions provided functionalized 2,3-dihydrobenzofurans in good yields for a variety of o-hydroxyaromatic α,β-unsaturated aldehydes. Current work focuses on expanding the scope of this reaction to other substrates such as sulfur yields, and on developing an efficient catalytic asymmetric variant. 2,3-Dihydrobenzofurans are found in numerous biologically active natural products and synthetic compounds. These are an attractive type of oxygenated compound because their basic core skeleton is present in neolignans, pterocarpans, and synthetic drugs used in the treatment of pulmonary hypertension, atherosclerotic peripheral arterial disease, and central nervous system trauma and ischemia. Owing to the importance of their structures, numerous synthetic methods for 2,3-dihydrobenzofurans have been developed, primarily: radical cyclizations, Lewis acid promoted reactions, anionic cyclizations, and transition-metal catalyzed processes. However, these methods cannot be generalized as much as is desirable, and they yielded poor chemo- and/or stereoselectivities. Hence, the development of an efficient enantioselective synthetic method for obtaining 2,3-dihydrobenzofuran scaffolds attracted our attention.

  1. NaBH4/NaNO3/H2O: A Convenient System for Selective Reduction of Aldehydes VS. Ketones to their Corresponding Alcohols

    Directory of Open Access Journals (Sweden)

    Soheila Ghaderi


    Full Text Available NaBH4 (1.25 equivalents & NaNO3 (3 equivalents reduce a variety of aldehydes in the presence of ketones to their corresponding alcohols. Also, regioselectivity and exclusive 1,2-reduction enals to their corresponding allylic alcohols in high to excellent yields was achieved successfully with this reducing system. The reduction reactions were carried out in water as green solvent in high to excellent yields of the products. A nitrate-borane complex [H3B-NO3]Na is possibly the active reductant in the reaction mixture.

  2. Silver(I)-Catalyzed Synthesis of β-Oxopropylcarbamates from Propargylic Alcohols and CO2 Surrogate: A Gas-Free Process. (United States)

    Song, Qing-Wen; Zhou, Zhi-Hua; Yin, Hong; He, Liang-Nian


    The utilization of carbon dioxide poses major challenges owing to its high thermodynamic stability and kinetic inertness. To circumvent these problems, a simple reaction system is reported comprising ammonium carbamates as carbon dioxide surrogates, propargylic alcohols, and a silver(I) catalyst, for the effective conversion of a wide range of alcohols and secondary amines into the corresponding β-oxopropylcarbamates. A key feature of this strategy includes quantitative use of a carbon resource with high product yields under gas-free and mild reaction conditions. Notably, this catalytic protocol also works well for the carboxylative cyclization of propargylic amines and carbon dioxide surrogates to afford 2-oxazolidinones.

  3. The Reaction of Allyl Isothiocyanate with Hydroxyl/Water and β-Cyclodextrin Using Ultraviolet Spectrometry

    Directory of Open Access Journals (Sweden)

    Zi-Tao Jiang


    Full Text Available The reaction of allyl isothiocyanate (AITC with hydroxyl/water and β-cyclodextrin (β-CD in different acidic-alkaline media has been investigated by ultraviolet spectrometry. The kinetic parameters of the reaction were measured. It was found that after AITC translating into thiourea, the absorption peak shifted from 240 to 226 nm and the molar absorptivity increased about 16 times. The reaction can be seen as a pseudo first order reaction because the concentration of hydroxyl was constant. β-CD can inhibit the reaction of AITC with hydroxyl/water, i.e. the hydrolysis of AITC. The formation constant (Ka and thermodynamic parameters of the complex reaction were calculated. Ka decreased with the increase of temperature. The experimental results indicated that the inclusive process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution.

  4. An Efficient Amide-Aldehyde-Alkene Condensation: Synthesis for the N-Allyl Amides. (United States)

    Quan, Zheng-Jun; Wang, Xi-Cun


    The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well-recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid-catalyzed N-allylation of electron-poor N-heterocyclic amides and sulfonamide via an amide-aldehyde-alkene condensation reaction. The substrate scope with respect to N-heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N-methyl-1-naphthamide or methyl (naphthalene-1-ylmethyl)carbamate, with paraformaldehyde and styrene in a one-pot manner.

  5. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    KAUST Repository

    Behenna, Douglas C.


    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. © 2012 Macmillan Publishers Limited. All rights reserved.

  6. Low-temperature Electrodeposition of Aluminium from Lewis Acidic 1-Allyl-3-methylimidazolium Chloroaluminate Ionic Liquids

    Institute of Scientific and Technical Information of China (English)

    郑勇; 张锁江; 吕兴梅; 王倩; 左勇; 刘恋


    Lewis acidic 1-allyl-3-methylimidazolium chloroaluminate ionic liquids were used as promising electrolytes in the low-temperature electrodeposition of aluminium. Systematic studies on deposition process have been performed by cYClic voltammetry and chronoamperometry. The surface morphology and X-ray diffraction (XRD) patterns of deposits prepared at different experimental conditions were also investigated. It was shown that the nucleation density and growth rate of crystallites had a great effect on the structure of aluminium deposited. The crys- tallographic orientation of deposits was mainly influenced by temperature and current density. Smooth, dense and well adherent aluminium coatings were obtained on copper substrates at 10-25^-2 and 313.2-353.2 K. More- over, the current efficiency of deposition and purity of aluminium have been significantly improved, demonstrating that the ionic liquids tested have a prospectful potential in electroplating and electrorefining of aluminium.

  7. Decarboxylative-coupling of allyl acetate catalyzed by group 10 organometallics, [(phen)M(CH3)]+. (United States)

    Woolley, Matthew; Ariafard, Alireza; Khairallah, George N; Kwan, Kim Hong-Yin; Donnelly, Paul S; White, Jonathan M; Canty, Allan J; Yates, Brian F; O'Hair, Richard A J


    Gas-phase carbon-carbon bond forming reactions, catalyzed by group 10 metal acetate cations [(phen)M(O2CCH3)](+) (where M = Ni, Pd or Pt) formed via electrospray ionization of metal acetate complexes [(phen)M(O2CCH3)2], were examined using an ion trap mass spectrometer and density functional theory (DFT) calculations. In step 1 of the catalytic cycle, collision induced dissociation (CID) of [(phen)M(O2CCH3)](+) yields the organometallic complex, [(phen)M(CH3)](+), via decarboxylation. [(phen)M(CH3)](+) reacts with allyl acetate via three competing reactions, with reactivity orders (% reaction efficiencies) established via kinetic modeling. In step 2a, allylic alkylation occurs to give 1-butene and reform metal acetate, [(phen)M(O2CCH3)](+), with Ni (36%) > Pd (28%) > Pt (2%). Adduct formation, [(phen)M(C6H11O2)](+), occurs with Pt (24%) > Pd (21%) > Ni(11%). The major losses upon CID on the adduct, [(phen)M(C6H11O2)](+), are 1-butene for M = Ni and Pd and methane for Pt. Loss of methane only occurs for Pt (10%) to give [(phen)Pt(C5H7O2)](+). The sequences of steps 1 and 2a close a catalytic cycle for decarboxylative carbon-carbon bond coupling. DFT calculations suggest that carbon-carbon bond formation occurs via alkene insertion as the initial step for all three metals, without involving higher oxidation states for the metal centers.

  8. A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis. (United States)

    Gao, Fang; Carr, James L; Hoveyda, Amir H


    A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

  9. The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

    Directory of Open Access Journals (Sweden)

    Tom Willemse


    Full Text Available The (site-selective derivatization of amino acids and peptides represents an attractive field with potential applications in the establishment of structure–activity relationships and labeling of bioactive compounds. In this respect, bioorthogonal cross-coupling reactions provide valuable means for ready access to peptide analogues with diversified structure and function. Due to the complex and chiral nature of peptides, mild reaction conditions are preferred; hence, a suitable cross-coupling reaction is required for the chemical modification of these challenging substrates. The Suzuki reaction, involving organoboron species, is appropriate given the stability and environmentally benign nature of these reactants and their amenability to be applied in (partial aqueous reaction conditions, an expected requirement upon the derivatization of peptides. Concerning the halogenated reaction partner, residues bearing halogen moieties can either be introduced directly as halogenated amino acids during solid-phase peptide synthesis (SPPS or genetically encoded into larger proteins. A reversed approach building in boron in the peptidic backbone is also possible. Furthermore, based on this complementarity, cyclic peptides can be prepared by halogenation, and borylation of two amino acid side chains present within the same peptidic substrate. Here, the Suzuki–Miyaura reaction is a tool to induce the desired cyclization. In this review, we discuss diverse amino acid and peptide-based applications explored by means of this extremely versatile cross-coupling reaction. With the advent of peptide-based drugs, versatile bioorthogonal conversions on these substrates have become highly valuable.

  10. Intramolecular cyclization of aspartic acid residues assisted by three water molecules: a density functional theory study (United States)

    Takahashi, Ohgi; Kirikoshi, Ryota


    Aspartic acid (Asp) residues in peptides and proteins (l-Asp) are known to undergo spontaneous nonenzymatic reactions to form l-β-Asp, d-Asp, and d-β-Asp residues. The formation of these abnormal Asp residues in proteins may affect their three-dimensional structures and hence their properties and functions. Indeed, the reactions have been thought to contribute to aging and pathologies. Most of the above reactions of the l-Asp residues proceed via a cyclic succinimide intermediate. In this paper, a novel three-water-assisted mechanism is proposed for cyclization of an Asp residue (forming a gem-diol precursor of the succinimide) by the B3LYP/6-31 + G(d,p) density functional theory calculations carried out for an Asp-containing model compound (Ace-Asp-Nme, where Ace = acetyl and Nme = NHCH3). The three water molecules act as catalysts by mediating ‘long-range’ proton transfers. In the proposed mechanism, the amide group on the C-terminal side of the Asp residue is first converted to the tautomeric iminol form (iminolization). Then, reorientation of a water molecule and a conformational change occur successively, followed by the nucleophilic attack of the iminol nitrogen on the carboxyl carbon of the Asp side chain to form the gem-diol species. A satisfactory agreement was obtained between the calculated and experimental energetics.

  11. Synthesis of Bridgehead Nitrogen Heterocycles via Cyclization of alpha-Ammonio 5-Hexenyl Radicals. (United States)

    Della, Ernest W.; Smith, Paul A.


    Ring-closure of the 2,2-dimethyl-2-azonia-5-hexenyl radical (4) proceeds smoothly and efficiently to give the 5-exo isomer essentially quantitatively, in accordance with predictions based on MP4SDTQ/6-31G ab initio calculations on the thermodynamic stability of alpha-ammonio radicals. The corresponding 5-hexynyl radical species 15 and its 6-phenyl derivative 19 display similar behavior affording the analogous 5-exo-3-methylenepyrrolidinium salts in high yield. In none of these cases were the products of reduction were detected. All of the radical intermediates were generated conveniently by treatment of the iodomethyl and/or phenylselenomethyl salts with tributyltin hydride. Application of this procedure to monocyclic precursors such as 1-methyl-1-iodomethyl-4-methylene-1-azoniacyclohexyl iodide (31) provided an attractive entry into quaternary derivatives of the 1-azabicyclo[2.2.1]heptyl system in good yield via a three-step sequence from 1-methylpiperidone. Dequaternization of the bicyclic salts so obtained unexpectedly leads to rupture of one of the rings rather than loss of the N-methyl group. The 1-azabicyclo[2.2.1]heptane could be accessed readily via tin hydride-induced cyclization of the corresponding N-phenylethylammonium salt 54, followed by Hofmann elimination with potassium tert-butoxide.

  12. Alcoholic liver disease (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  13. Breath alcohol test (United States)

    Alcohol test - breath ... There are various brands of breath alcohol tests. Each one uses a different method to test the level of alcohol in the breath. The machine may be electronic or manual. One ...

  14. Behind the Label "Alcoholic." (United States)

    Wright, Deborah M.


    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  15. On the Nature of the Intermediates and the Role of Chloride Ions in Pd-Catalyzed Allylic Alkylations: Added Insight from Density Functional Theory

    DEFF Research Database (Denmark)

    Fristrup, Peter; Ahlquist, Mårten Sten Gösta; Tanner, David Ackland


    The reactivity of intermediates in palladium-catalyzed allylic alkylation was investigated using DFT (B3LYP) calculations including a PB-SCRF solvation model. In the presence of both phosphine and chloride ligands, the allyl intermediate is in equilibrium between a cationic eta(3)-allylPd complex...... with two phosphine ligands, the corresponding neutral complex with one phosphine and one chloride ligand, and a neutral eta(1)-allylPd complex with one chloride and two phosphine ligands. The eta(1)-complex is unreactive toward nucleophiles. The cationic eta(3)-complex is the intermediate most frequently...... invoked in the title reaction, but in the presence of halides, the neutral, unsymmetrically substituted eta(3)-CoMplex will be formed rapidly from anionic Pd(0) complexes in solution. Since the latter will prefer both leaving group ionization and reaction with nucleophiles in the position trans...

  16. Modular access to vicinally functionalized allylic (thio)morpholinonates and piperidinonates by substrate-controlled annulation of 1,3-azadienes with hexacyclic anhydrides. (United States)

    Braunstein, Hannah; Langevin, Spencer; Khim, Monique; Adamson, Jonathan; Hovenkotter, Katie; Kotlarz, Lindsey; Mansker, Brandon; Beng, Timothy K


    A modular substrate-controlled hexannulation of inherently promiscuous 1,3-azadienes with hexacyclic anhydrides, which affords versatile vicinally functionalized allylic lactams, in high yields, regio- and stereoselectivities is described.

  17. Genetics and alcoholism


    Edenberg, Howard J; Foroud, Tatiana


    Alcohol is widely consumed, but excessive use creates serious physical, psychological and social problems and contributes to many diseases. Alcoholism (alcohol dependence, alcohol use disorders) is a maladaptive pattern of excessive drinking leading to serious problems. Abundant evidence indicates that alcoholism is a complex genetic disease, with variations in a large number of genes affecting risk. Some of these genes have been identified, including two genes of alcohol me...


    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova


    Full Text Available The article considers the questions of the relationship between the amount of the consumed alcohol, the type of alcoholic beverage, pattern of alcohol consumption and the blood pressure level. The article presents data on the positive effect of alcohol intake restrictions and recommendations for permissible limits of alcohol consumption. New possibilities of drug therapy aimed at limiting alcohol consumption are being reported.

  19. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren


    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may...... be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking...... and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men...

  20. Oxidation reaction of 4-allyl-4-hydroperoxy-2-methoxycyclohexa-2,5-dienone in the presence of potassium permanganate without a co-oxidant

    Directory of Open Access Journals (Sweden)

    Mehmet Serdar Gültekin


    Full Text Available 4-Allyl-4-hydroperoxy-2-methoxycyclohexa-2,5-dienone (5 was synthesized by photooxygenation of commercially available Eugenol in the presence of tetraphenylporphyrin (TPP as a singlet oxygen sensitizer. The brief and one-pot syntheses of some natural product skeletons were conducted using the corresponding allylic hydroperoxide at different temperatures (0 oC and room temperature with potassium permanganate (KMnO 4 in mild condition at N 2(g atm.

  1. A convenient and stereoselective synthesis of (Z)-allyl selenides via Sm/TMSCI system-promoted coupling of Baylis-Hillman adducts with diselenides

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-kui; XU Dan-qian; XU Zhen-yuan; ZHANG Yong-min


    A simple and convenient procedure for stereoselective synthesis of (Z)-allyl selenides has been developed by a one-pot reaction of diselenides with Baylis-Hillman adducts in the presence of samarium metal-trimethylsilyl chloride under mild conditions. Presumably, the diselenides are cleaved by Sm/TMSCl system to form selenide anions, which then undergo SN2' substitution of Baylis-Hillman adducts to produce the (Z)-allyl selenides.

  2. Free-Radical Triggered Ordered Domino Reaction: An Approach to C-C Bond Formation via Selective Functionalization of α-Hydroxyl-(sp(3))C-H in Fluorinated Alcohols. (United States)

    Xu, Zhengbao; Hang, Zhaojia; Liu, Zhong-Quan


    A free-radical mediated highly ordered radical addition/cyclization/(sp(3))C-C(sp(3)) formation domino reaction is developed. Three new C-C bonds are formed one by one in a mixed system. Furthermore, it represents the first example of cascade C-C bond formation via selective functionalization of α-hydroxyl-C(sp(3))-H in fluorinated alcohols.


    Institute of Scientific and Technical Information of China (English)

    K.C. Gupta; H.K. Abdulkadir; S. Chand


    A new chelating polymer support has been prepared by suspension copolymeriz a tion of synthesized N,N'-bis(3-allyl salicylidene)ethylenediamine monomer Schiff base (N,N'-BSEDA) with styrene (St) and divinylbenzene (DVB) using azobisisobutyronitrile (AIBN) as initiator in the presence of poly(vinyl alcohol). The content and complexation ability of monomer Schiff base (N,N'-BSEDA) for cobalt(II) ions in prepared crosslinked polymer beads have shown dependence on the amount of DVB used in reaction mixture. The amount of monomer Schiff base (N,N'-BSEDA) in crosslinked beads showed a substantial decreasing trend at high concentration of DVB in the reaction mixture (> 1.5 mol dm-3), hence the efficiency of complexation (EC%) and cobalt(II) ion loading (EL%) of polymer beads showed a decreasing trend. The structure of monomer Schiff base (N,N'-BSEDA) and its cobalt(II) complex on polymer support was elucidated by IR, UV and magnetic measurements. The catalytic activity of polymer bound cobalt(Ⅱ) Schiff base complex was evaluated by analyzing kinetic data of decomposition of hydrogen peroxide in the presence of either supported cobalt (II) complex or free cobalt(II) complex. The activation energy for the decomposition of hydrogen peroxide by polymer supported cobalt(II)complex was found to be low (33.37 kJ mol-l) in comparison with unsupported cobalt(II) complex (56.35 kJ mol-1). On the basis of experimental observations, reaction steps are proposed and a suitable rate expression derived.

  4. Alcohol Alert: Link Between Stress and Alcohol (United States)

    ... body at even greater risk for harm. Ongoing stress, or chronic, heavy alcohol use, may impair the body’s ability ... J.A., and Chard, K.M. Alcohol and stress in the military. Alcohol Research: ... suicide ideation and attempts associated with adverse childhood experiences. ...

  5. Health risks of alcohol use (United States)

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  6. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.


    Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white...... men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence......, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1...


    Institute of Scientific and Technical Information of China (English)

    Rui-qiang Kou; Chao Qu; Zhi-kang Xu; You-yi Xu; Ke Yao


    In this work, the surface properties of novel sugar-containing polymers, α-allyl glucoside (AG)/acrylonitrile (AN)copolymers, were studied by contact angle, protein adsorption and cell adhesion measurements. It was found that the contact angle of the copolymer films decreased from 68° to 30° with the increase of AG content in the copolymer. The adsorption amount of bovine serum albumin (BSA) and the adhesive macrophage onto the film surface also decreased significantly with increasing α-allyl glucoside content from 0 to 42 wt% in the copolymer. These preliminary results reveal that both the hydrophilicity and the biocompatibility of polyacrylonitrile-based membranes could be improved by copolymerizing acrylonitrile with vinyl carbohydrates.

  8. One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters (United States)

    Silveira-Dorta, Gastón; Álvarez-Méndez, Sergio J; Martín, Víctor S


    Summary An improved protocol for the synthesis of enantiomerically pure allylic amines is reported. N-Protected α-amino esters derived from natural amino acids were submitted to a one-pot tandem reduction–olefination process. The sequential reduction with DIBAL-H at −78 °C and subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner–Wadsworth–Emmons organophosphorus reagents. A better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine and threonine derivatives. PMID:27340486

  9. Crystal structure of (Z-3-allyl-5-(3-bromobenzylidene-2-sulfanylidene-1,3-thiazolidin-4-one

    Directory of Open Access Journals (Sweden)

    Rahhal El Ajlaoui


    Full Text Available In the title compound, C13H10BrNOS2, the rhodanine (systematic name: 2-sulfanylidene-1,3-thiazolidin-4-one and the 3-bromobenzylidene ring systems are inclined slightly, forming a dihedral angle of 5.86 (12°. The rhodanine moiety is linked to an allyl group at the N atom and to the 3-bromobenzylidene ring system. The allyl group, C=C—C, is nearly perpendicular to the mean plane through the rhodanine ring, maling a dihedral angle of 87.2 (5°. In the crystal, molecules are linked by pairs of C—H...O hydrogen bonds, forming inversion dimers with an R22(10 ring motif.

  10. Allyl group as a protecting group for internucleotide phosphate and thiophosphate linkages in oligonucleotide synthesis: facile oxidation and deprotection conditions. (United States)

    Manoharan, M; Lu, Y; Casper, M D; Just, G


    [reaction: see text] The allyl group, which serves as a protecting group for an internucleotide bond for both phosphates and phosphorothioates, can be easily removed by good nucleophiles under weakly basic or neutral conditions. For a practical synthesis on solid support, camphorsulfonyloxaziridine was used as the oxidizing agent for synthesizing DNA, while the Beaucage reagent was used for preparing phosphorothioate oligomers. Both types of oligonucleotides were easily deprotected by concentrated ammonium hydroxide containing 2% mercaptoethanol.

  11. Insights into Diterpene Cyclization from Structure of Bifunctional Abietadiene Synthase from Abies grandis

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Ke; Gao, Yang; Hoy, Julie A.; Mann, Francis M.; Honzatko, Richard B.; Peters, Reuben J. (Iowa State)


    Abietadiene synthase from Abies grandis (AgAS) is a model system for diterpene synthase activity, catalyzing class I (ionization-initiated) and class II (protonation-initiated) cyclization reactions. Reported here is the crystal structure of AgAS at 2.3 {angstrom} resolution and molecular dynamics simulations of that structure with and without active site ligands. AgAS has three domains ({alpha}, {beta}, and {gamma}). The class I active site is within the C-terminal {alpha} domain, and the class II active site is between the N-terminal {gamma} and {beta} domains. The domain organization resembles that of monofunctional diterpene synthases and is consistent with proposed evolutionary origins of terpene synthases. Molecular dynamics simulations were carried out to determine the effect of substrate binding on enzymatic structure. Although such studies of the class I active site do lead to an enclosed substrate-Mg{sup 2+} complex similar to that observed in crystal structures of related plant enzymes, it does not enforce a single substrate conformation consistent with the known product stereochemistry. Simulations of the class II active site were more informative, with observation of a well ordered external loop migration. This 'loop-in' conformation not only limits solvent access but also greatly increases the number of conformational states accessible to the substrate while destabilizing the nonproductive substrate conformation present in the 'loop-out' conformation. Moreover, these conformational changes at the class II active site drive the substrate toward the proposed transition state. Docked substrate complexes were further assessed with regard to the effects of site-directed mutations on class I and II activities.

  12. Insights into Diterpene Cyclization from Structure of Bifunctional Abietadiene Synthase from Abies grandis* (United States)

    Zhou, Ke; Gao, Yang; Hoy, Julie A.; Mann, Francis M.; Honzatko, Richard B.; Peters, Reuben J.


    Abietadiene synthase from Abies grandis (AgAS) is a model system for diterpene synthase activity, catalyzing class I (ionization-initiated) and class II (protonation-initiated) cyclization reactions. Reported here is the crystal structure of AgAS at 2.3 Å resolution and molecular dynamics simulations of that structure with and without active site ligands. AgAS has three domains (α, β, and γ). The class I active site is within the C-terminal α domain, and the class II active site is between the N-terminal γ and β domains. The domain organization resembles that of monofunctional diterpene synthases and is consistent with proposed evolutionary origins of terpene synthases. Molecular dynamics simulations were carried out to determine the effect of substrate binding on enzymatic structure. Although such studies of the class I active site do lead to an enclosed substrate-Mg2+ complex similar to that observed in crystal structures of related plant enzymes, it does not enforce a single substrate conformation consistent with the known product stereochemistry. Simulations of the class II active site were more informative, with observation of a well ordered external loop migration. This “loop-in” conformation not only limits solvent access but also greatly increases the number of conformational states accessible to the substrate while destabilizing the nonproductive substrate conformation present in the “loop-out” conformation. Moreover, these conformational changes at the class II active site drive the substrate toward the proposed transition state. Docked substrate complexes were further assessed with regard to the effects of site-directed mutations on class I and II activities. PMID:22219188

  13. Synchrotron Photoionization Mass Spectrometry Measurements of Kinetics and Product Formation in the Allyl Radical (H2CCHCH2)Self Reaction (United States)

    Selby, Talitha M.; Melini, giovanni; Goulay, Fabien; Leone, Stephen R.; Fahr, Askar; Taatjes, Craig A.; Osborn, David L.


    Product channels for the self-reaction of the resonance-stabilized allyl radical, C3H5 + C3H5, have been studied with isomeric specificity at temperatures from 300-600 K and pressures from 1-6 Torr using time-resolved multiplexed photoionization mass spectrometry. Under these conditions 1,5-hexadiene was the only C6H10 product isomer detected. The lack of isomerization of the C6H10 product is in marked contrast to the C6H6 product in the related C3H3 + C3H3 reaction, and is due to the more saturated electronic structure of the C6H10 system. The disproportionation product channel, yielding allene + propene, was also detected, with an upper limit on the branching fraction relative to recombination of 0.03. Analysis of the allyl radical decay at 298 K yielded a total rate coefficient of (2.7 +/- 0.8) x 10(exp -11) cu cm/molecule/s, in good agreement with pre.vious experimental measurements using ultraviolet kinetic absorption spectroscopy and a recent theoretical determination using variable reaction coordinate transition state theory. This result provides independent indirect support for the literature value of the allyl radical ultraviolet absorption cross-section near 223 nm.

  14. Biosynthesis of monoterpenes. Stereochemistry of the enzymatic cyclizations of geranyl pyrophosphate to (+)-alpha-pinene and (-)-beta-pinene

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.; Satterwhite, D.M.; Wheeler, C.J.; Felton, N.M.


    The conversion of geranyl pyrophosphate to (+)-alpha-pinene and to (-)-beta-pinene is considered to proceed by the initial isomerization of the substrate to (-)-(3R)- and to (+)-(3S)-linalyl pyrophosphate, respectively, and the subsequent cyclization of the anti, endo-conformer of these bound intermediates by mirror-image sequences which should result in the net retention of configuration at C1 of the geranyl precursor. Incubation of (1R)-(2-14C,1-3H)- and (1S)-(2-14C,1-3H)geranyl pyrophosphate with (+)-pinene cyclase and with (-)-pinene cyclase from common sage (Salvia officinalis) gave labeled (+)-alpha- and (-)-beta-pinene of unchanged 3H/14C ratio in all cases, and the (+)- and (-)-olefins were stereoselectively converted to (+)- and (-)-borneol, respectively, which were oxidized to the corresponding (+)- and (-)-isomers of camphor, again without change in isotope ratio. The location of the tritium was determined in each case by stereoselective, base-catalyzed exchange of the exo-alpha-hydrogens of these derived ketones. The results indicated that the configuration at C1 of the substrate was retained in the enzymatic transformations to the (+)- and (-)-pinenes, which is entirely consistent with the syn-isomerization of geranyl pyrophosphate to linalyl pyrophosphate, transoid to cisoid rotation, and anti, endo-cyclization of the latter. The absolute stereochemical elements of the antipodal reaction sequences were confirmed by the selective enzymatic conversions of (3R)- and (3S)-1Z-(1-3H)linalyl pyrophosphate to (+)-alpha-pinene and (-)-beta-pinene, respectively, and by the location of the tritium in the derived camphors as before. The summation of the results fully defines the overall stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to the antipodal pinenes.

  15. Alcohol and Breastfeeding

    DEFF Research Database (Denmark)

    Haastrup, Maija Bruun; Pottegård, Anton; Damkier, Per


    While the harmful effects of alcohol during pregnancy are well-established, the consequences of alcohol intake during lactation have been far less examined. We reviewed available data on the prevalence of alcohol intake during lactation, the influence of alcohol on breastfeeding......, the pharmacokinetics of alcohol in lactating women and nursing infants and the effects of alcohol intake on nursing infants. A systematic search was performed in PubMed from origin to May 2013, and 41 publications were included in the review. Approximately half of all lactating women in Western countries consume...... alcohol while breastfeeding. Alcohol intake inhibits the milk ejection reflex, causing a temporary decrease in milk yield. The alcohol concentrations in breast milk closely resemble those in maternal blood. The amount of alcohol presented to nursing infants through breast milk is approximately 5...

  16. Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes (United States)

    Díaz, Jimena E; Mollo, María C


    Summary The first general procedure for the synthesis of 5 to 7-membered 1-aryl-2-iminoazacycloalkanes is presented, by microwave-assisted ring closure of ω-arylaminonitriles promoted by polyphosphoric acid (PPA) esters. 1-Aryl-2-iminopyrrolidines were easily prepared from the acyclic precursors employing a chloroformic solution of ethyl polyphosphate (PPE). The use of trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of 1-aryl-2-iminopiperidines and hitherto unreported 1-aryl-2-iminoazepanes. The cyclization reaction involves good to high yields and short reaction times, and represents a novel application of PPA esters in heterocyclic synthesis. PMID:27829907

  17. A Novel Reductive Cyclization of o-Nitrobenzamides and Ketones Promoted by Low-valent Titanium Reagent

    Institute of Scientific and Technical Information of China (English)

    SHI,Da-Qing(史达清); RONG,Liang-Ce(荣良策); WANG,Ju-Xian(王菊仙); ZHUANG,Qi-Ya(庄启亚); TU,Shu-Jiang(屠树江)


    A short and facile synthesis of a series of 1,2-dihydroquiazolin-4(3H)-ones was accomplished in good yields via novel reductive cyclization of o-nitrobenzamides with ketones promoted by TiCl4/Zn system. The structure was established on the basis of elemental analysis, IR, 1H NMR and confirmed by a single-crystal X-ray diffraction analysis. This method has the advantages of easily accessible starting materials, convenient manipulation and moderate to high yields.

  18. BiX3 and FeX3-Promoted Prins Cyclization of Enol Ethers in CH2Cl2

    Institute of Scientific and Technical Information of China (English)

    杨艺; 贾平敬; 刘素平; 于炜


    The Prins cyclization of enol ethers has been realized by employing BiX3 (or FeX3) as catalyst and TMSX (X = Br, C1) as the halogen source. The presence of a tiny amount of water in the solvent dichloromethane played a key role for the reaction to proceed. The reaction is believed to be catalyzed by Lewis acid-assisted Bronsted acids, which were generated in situ from MX3 and water in the solvent.

  19. Synthesis of a highly hydrophobic cyclic decapeptide by solid-phase synthesis of linear peptide and cyclization in solution

    Institute of Scientific and Technical Information of China (English)


    A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilizat...

  20. Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

    Directory of Open Access Journals (Sweden)

    Jimena E. Díaz


    Full Text Available The first general procedure for the synthesis of 5 to 7-membered 1-aryl-2-iminoazacycloalkanes is presented, by microwave-assisted ring closure of ω-arylaminonitriles promoted by polyphosphoric acid (PPA esters. 1-Aryl-2-iminopyrrolidines were easily prepared from the acyclic precursors employing a chloroformic solution of ethyl polyphosphate (PPE. The use of trimethylsilyl polyphosphate (PPSE in solvent-free conditions allowed for the synthesis of 1-aryl-2-iminopiperidines and hitherto unreported 1-aryl-2-iminoazepanes. The cyclization reaction involves good to high yields and short reaction times, and represents a novel application of PPA esters in heterocyclic synthesis.

  1. Regioselective synthesis of 2H-indazoles using a mild, one-pot condensation-Cadogan reductive cyclization. (United States)

    Genung, Nathan E; Wei, Liuqing; Aspnes, Gary E


    An operationally simple and efficient one-pot synthesis of 2H-indazoles from commercially available reagents is reported. Ortho-imino-nitrobenzene substrates, generated via condensation, undergo reductive cyclization promoted by tri-n-butylphosophine to afford substituted 2H-indazoles under mild reaction conditions. A variety of electronically diverse ortho-nitrobenzaldehydes and anilines were examined. To further extend the scope of the transformation, aliphatic amines were also employed to form N2-alkyl indazoles selectively under the optimized reaction conditions.

  2. Unexpected Formation of Highly Functionalized Dihydropyrans via Addition-Cyclization Reactions Between Dimethyl Oxoglutaconate and α,β-Unsaturated Hydrazones. (United States)

    Mullins, Jason E; Etoga, Jean-Louis G; Gajewski, Mariusz; Degraw, Joseph I; Thompson, Charles M


    The condensation between dienophiles and α,β-unsaturated hydrazone azadienes was previously reported to afford piperidines. During an attempt to adapt this reaction to the preparation of piperidine-based conformationally-restricted analogs of glutamate, it was discovered that the electrophile, dimethyl oxoglutaconate (DOG) led to highly substituted dihydropyrans in 20-50% yield. The unexpected pyran product likely results from an initial 1,4-addition of the hydrazone to the oxoglutaconate followed by intramolecular cyclization of the resultant enolate oxygen to the α,β-unsaturated iminium ion. Further manipulations afford substituted tetrahydropyran 6-methamino-2,4-dicarboxylic acids.

  3. Palladium-catalyzed Carbonylative Cyclization of 2-Bromocyclohex-1-enecarbalde-hydes with Aliphatic Primary Amines Leading to 3-Aminohydroisoindol-1-ones

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Yeon Kyu; Cho, Chan Sik; Yoon, Nam Sik [Kyungpook National Univ., Daegu (Korea, Republic of)


    It has been shown that 2-bromocyclohex-1-enecarbaldehydes, which are readily prepared from α-methylene containing cyclohexanones under the bromination conditions of Vilsmeier-Haak reaction, undergo carbonylative cyclization with aliphatic primary amines in the presence of a palladium catalyst and a bidentate phosphorus ligand to give 3-aminohydroisoindol-1-ones. The present reaction provides a promising route for the synthesis of valuable heterocycles from readily available starting ketones. Further study of synthetic applications to heterocycles using these ketones is currently under investigation. Palladium-catalyzed carbonylation of organic halides (or triflates) followed by intramolecular cyclization (carbonyl-ative cyclization) has been widely explored and used as a promising synthetic tool for the construction of the structural core of many pharmacologically and biologically active lactones and lactams.

  4. 烯丙基酚醛树脂的固化动力学%Curing Kinetics of Allyl Phenolic Resin

    Institute of Scientific and Technical Information of China (English)

    刘洋; 刘诗薇; 李志强; 于景坤


    The curing behavior of allyl phenolic resin was analyzed at different heating rates using differential scanning calorimetry.The obtained kinetic data were treated by Kissinger and KAS(Kissinger-Akahira-Sunose) methods to obtain the curing reaction kinetic parameters.A curing kinetics model was established for allyl phenolic resin.Compared with phenolic resin,the curing temperature of allyl phenolic resin is higher,the reaction order is closer to 1,and the average activation energy of the curing reaction is lower,111.45 kJ/mol.The activation energy of allyl phenolic resin is almost constant and changes little with temperature in the curing process.The curing kinetics model of allyl phenolic resin provides a theoretical basis for the study of curing process parameters.%利用差示扫描量热法分析了烯丙基酚醛树脂在不同升温速率下的固化行为,用Kissinger法和KAS(Kissinger-Akahira-Sunose)法对获得的动力学数据进行处理,得到了固化反应动力学参数,并建立了烯丙基酚醛树脂的固化动力学模型.结果表明:与纯酚醛树脂相比,烯丙基酚醛树脂固化温度较高,反应级数更接近于1,固化反应所需的平均表观活化能较低,为111.45kJ/mol;在整个固化过程中,烯丙基酚醛树脂的活化能较为恒定,随温度变化不大;烯丙基酚醛树脂固化动力学模型为研究该体系固化工艺参数提供了理论依据.

  5. On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update. (United States)

    Colín-González, Ana Laura; Ali, Syed F; Túnez, Isaac; Santamaría, Abel


    Therapeutic approaches based on isolated compounds obtained from natural products to handle central and peripheral disorders involving oxidative stress and inflammation are more common nowadays. The validation of nutraceutics vs. pharmaceutics as tools to induce preventive and protective profiles in human health alterations is still far of complete acceptance, but the basis to start more solid experimental and clinical protocols with natural products has already begun. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound exhibiting a considerable number of positive actions in cell models and living systems. An update, in the form of review, is needed from time to time to get access to the state-of-the-art on this topic. In this review we visited recent and refreshing evidence of new already proven and potential targets to explain the benefits of using SAC against toxic and pathological conditions. The broad spectrum of protective actions covered by this molecule comprises antioxidant, redox modulatory and anti-inflammatory activities, accompanied by anti-apoptotic, pro-energetic and signaling capacities. Herein, we detail the evidence on these aspects to provide the reader a more complete overview on the promising aspects of SAC in research.

  6. Merging allylic carbon-hydrogen and selective carbon-carbon bond activation (United States)

    Masarwa, Ahmad; Didier, Dorian; Zabrodski, Tamar; Schinkel, Marvin; Ackermann, Lutz; Marek, Ilan


    Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C-H and C-C bonds, instead of the conventional construction of new C-C bonds. Here we present an approach that exploits the multifold reactivity of easily accessible substrates with a single organometallic species to furnish complex molecular scaffolds through the merging of otherwise difficult transformations: allylic C-H and selective C-C bond activations. The resulting bifunctional nucleophilic species, all of which have an all-carbon quaternary stereogenic centre, can then be selectively derivatized by the addition of two different electrophiles to obtain more complex molecular architecture from these easily available starting materials.

  7. Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles. (United States)

    Malik, Hasnain A; Taylor, Buck L H; Kerrigan, John R; Grob, Jonathan E; Houk, K N; Du Bois, J; Hamann, Lawrence G; Patterson, Andrew W


    We outline a strategy to enable non-directed Pd(II)-catalyzed C-H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C-H acetoxylation reactions, addition of a variety of N-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of allylic C-H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 provide an inverse correlation of the computed heterocycle-Pd(OAc)2 binding affinities with the experimental conversions to products. Additionally, (1)H NMR binding studies provide experimental support for theoretical calculations.

  8. Allyl functionalized phosphinite and phosphonite ligands: Synthesis, transition metal chemistry and orthopalladation reactions

    Indian Academy of Sciences (India)

    Singappagudem Govindaraju; Guddekoppa S Ananthnag; Susmita Naik; Shaikh M Mobin; Maravanji S Balakrishn


    Allyl functionalized phosphinite PPh2(OAr) [Ar=C6H4(-C3H5)] (1) and phosphonite PPh(OAr)2 (2) ligands were prepared by the reactions of 2-allylphenol with PPh2Cl and PPhCl2, respectively. The ruthenium(II) complexes, [Ru(6--cymene)(PPh2(OAr))Cl2] (3) and [Ru(6--cymene)(PPh(OAr)2Cl2)] (4) were obtained by reacting 1 or 2 with [Ru(6--cymene)Cl2]2 in 2:1 molar ratios, respectively. Reactions of 1 or 2 with AuCl(SMe2) gave [Au{PPh2(OAr)}Cl] (5) or [Au{PPh(OAr)2}Cl] (6) in good yield. The palladium complex, [Pd{PPh(OAr)2}2Cl2] (7) was prepared by reacting Pd(COD)Cl2 with 2 in 1:2 molar ratio. The reaction between Pd(COD)Cl2 and 1 yielded a mixture of orthopalladated cis- and trans-[Pd(Ph2P(OAr))Cl]2 (8a and 8b). The treatment of 8 with PPh3 and Ph2PCH2PPh2 resulted in the cleavage of chloro bridge to give respectively, [Ph2(OAr)PPd(PPh3)Cl] (9) and [Ph2(ArO)PPd(2-dppm)]OTf (10). Single crystal X-ray structure of the ruthenium complex 3 is described.

  9. Hydrolysis of cellulose catalyzed by quaternary ammonium perrhenates in 1-allyl-3-methylimidazolium chloride. (United States)

    Wang, Jingyun; Zhou, Mingdong; Yuan, Yuguo; Zhang, Quan; Fang, Xiangchen; Zang, Shuliang


    Quaternary ammonium perrhenates were applied as catalyst to promote the hydrolysis of cellulose in 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The quaternary ammonium perrhenates displayed good catalytic performance for cellulose hydrolysis. Water was also proven to be effective to promote cellulose hydrolysis. Accordingly, 97% of total reduced sugar (TRS) and 42% of glucose yields could be obtained under the condition of using 5mol% of tetramethyl ammonium perrhenate as catalyst, 70μL of water, ca. 0.6mmol of microcrystalline cellulose (MCC) and 2.0g of [Amim]Cl as solvent under microwave irradiation for 30min at 150°C (optimal conditions). The influence of quaternary ammonium cation on the efficiency of cellulose hydrolysis was examined based on different cation structures of perrhenates. The mechanism on perrhenate catalyzed cellulose hydrolysis is also discussed, whereas hydrogen bonding between ReO4 anion and hydroxyl groups of cellulose is assumed to be the key step for depolymerization of cellulose.

  10. Synergistic effect of allyl isothiocyanate (AITC) on cisplatin efficacy in vitro and in vivo. (United States)

    Ling, Xiang; Westover, David; Cao, Felicia; Cao, Shousong; He, Xiang; Kim, Hak-Ryul; Zhang, Yuesheng; Chan, Daniel Cf; Li, Fengzhi


    Although in vitro studies have shown that isothiocyanates (ITCs) can synergistically sensitize cancer cells to cisplatin treatment, the underlying mechanisms have not been well defined, and there are no in vivo demonstrations of this synergy. Here, we report the in vitro and in vivo data for the combination of allyl isothiocyanate (AITC), one of the most common naturally occurring ITCs, with cisplatin. Our study revealed that cisplatin and AITC combination synergistically inhibits cancer cell growth and colony formation, and enhances apoptosis in association with the downregulation of antiapoptotic proteins Bcl-2 and survivin. Importantly, the in vivo combination treatment suppresses human tumor growth in animal models without observable increases in toxicity (body weight loss) in comparison with single agent treatment. Furthermore, our data revealed that addition of AITC to cisplatin treatment changes the profile of G2/M arrest (e.g. increase in M phase cell number) and significantly extends the duration of G2/M arrest in comparison with cisplatin treatment alone. To explore the underlying mechanism, we found that AITC treatment rapidly depletes b-tubulin. Combination of AITC and cisplatin inhibits the expression of G2/M checkpoint-relevant proteins including CDC2, cyclin B1 and CDC25. Together, our findings reveal a novel mechanism for AITC enhancing cisplatin efficacy and provides the first in vivo evidence to support ITCs as potential candidates for developing new regimens to overcome platinum resistance.

  11. Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites.

    Directory of Open Access Journals (Sweden)

    Yang-Ji Kim

    Full Text Available Allyl-isothiocyanate (AITC is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH or N-acetylcysteine (NAC and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis.

  12. Allyl Isothiocyanate Inhibits Actin-Dependent Intracellular Transport in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Bjørnar Sporsheim


    Full Text Available Volatile allyl isothiocyanate (AITC derives from the biodegradation of the glucosinolate sinigrin and has been associated with growth inhibition in several plants, including the model plant Arabidopsis thaliana. However, the underlying cellular mechanisms of this feature remain scarcely investigated in plants. In this study, we present evidence of an AITC-induced inhibition of actin-dependent intracellular transport in A. thaliana. A transgenic line of A. thaliana expressing yellow fluorescent protein (YFP-tagged actin filaments was used to show attenuation of actin filament movement by AITC. This appeared gradually in a time- and dose-dependent manner and resulted in actin filaments appearing close to static. Further, we employed four transgenic lines with YFP-fusion proteins labeling the Golgi apparatus, endoplasmic reticulum (ER, vacuoles and peroxisomes to demonstrate an AITC-induced inhibition of actin-dependent intracellular transport of or, in these structures, consistent with the decline in actin filament movement. Furthermore, the morphologies of actin filaments, ER and vacuoles appeared aberrant following AITC-exposure. However, AITC-treated seedlings of all transgenic lines tested displayed morphologies and intracellular movements similar to that of the corresponding untreated and control-treated plants, following overnight incubation in an AITC-absent environment, indicating that AITC-induced decline in actin-related movements is a reversible process. These findings provide novel insights into the cellular events in plant cells following exposure to AITC, which may further expose clues to the physiological significance of the glucosinolate-myrosinase system.

  13. Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S. (Harvard-Med); (Mass. Gen. Hosp.); (UIC)


    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  14. Development and validation of a simple high performance liquid chromatography - evaporative light scattering detector method for direct quantification of native cyclodextrins in a cyclization medium. (United States)

    Rojas, Mayerlenis J; Castral, Thaís C; Giordano, Raquel L C; Tardioli, Paulo W


    A simple HPLC-ELSD method was developed for the separation and quantification of native cyclodextrins. The technique was validated in the presence of two interfering matrices composed of byproducts from the cyclization medium. A fast separation of the compounds was achieved (in cyclodextrins, and ≤6.2% for a blank matrix composed of a mixture of dextrin and glucose spiked with cyclodextrins. The limit of quantification was 0.05g/L for alpha- and 0.06g/L for beta- and gamma-cyclodextrins. The new HPLC-ELSD method could accurately quantify the three cyclodextrins directly in a cyclization medium, without pretreatment of the samples.

  15. Mechanistic and computational studies of exocyclic stereocontrol in the synthesis of bryostatin-like cis-2,6-disubstituted 4-alkylidenetetrahydropyrans by Prins cyclization. (United States)

    Ogawa, Yasuyuki; Painter, Phillip P; Tantillo, Dean J; Wender, Paul A


    The Prins cyclization of syn-β-hydroxy allylsilanes and aldehydes gives cis-2,6-disubstituted 4-alkylidenetetrahydropyrans as sole products in excellent yields regardless of the aldehyde (R″) or syn-β-hydroxy allylsilane substituent (R') used. By reversing the R″ and R' groups, complementary exocyclic stereocontrol can be achieved. When the anti-β-hydroxy allylsilanes are used, the Prins cyclization gives predominantly cis-2,6-disubstituted 4-alkylidenetetrahydropyrans, now with the opposite olefin geometry in excellent yield. The proposed reaction mechanism and the observed stereoselectivity for these processes are supported by DFT calculations.

  16. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes. (United States)

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten


    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

  17. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn


    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  18. Deciding to quit drinking alcohol (United States)

    ... quitting drinking; Quitting drinking; Quitting alcohol; Alcoholism - deciding to quit ... drinking problem when your body depends on alcohol to function and your drinking is causing problems with ...

  19. Diminished oligomerization in the synthesis of new anti-angiogenic cyclic peptide using solution instead of solid-phase cyclization. (United States)

    Rubio, Sandra; Clarhaut, Jonathan; Péraudeau, Elodie; Vincenzi, Marian; Soum, Claire; Rossi, Filomena; Guillon, Jean; Papot, Sébastien; Ronga, Luisa


    The design and synthesis of novel peptides that inhibit angiogenesis is an important area for anti-angiogenic drug development. Cyclic and small peptides present several advantages for therapeutic application, including stability, solubility, increased bio-availability and lack of immune response in the host cell. We describe here the synthesis and biological evaluations of a new cyclic peptide analog of CBO-P11: cyclo(RIKPHE), designated herein as CBO-P23M, a hexamer peptide encompassing residues 82 to 86 of VEGF which are involved in the interaction with VEGF receptor-2. CBO-P23M was prepared using in solution cyclization, therefore reducing the peptide cyclodimerization occurred during solid-phase cyclization. The cyclic dimer of CBO-P23M, which was obtained as the main side product during synthesis of the corresponding monomer, was also isolated and investigated. Both peptides markedly reduce VEGF-A-induced phosphorylation of VEGFR-2 and Erk1/2. Moreover, they exhibit anti-angiogenic activity in an in vitro morphogenesis study. Therefore CBO-P23M and CBO-P23M dimer appear as attractive candidates for the development of novel angiogenesis inhibitors for the treatment of cancer and other angiogenesis-related diseases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 368-375, 2016.

  20. Incorporation of N-amidino-pyroglutamic acid into peptides using intramolecular cyclization of alpha-guanidinoglutaric acid. (United States)

    Burov, Sergey; Moskalenko, Yulia; Dorosh, Marina; Shkarubskaya, Zoya; Panarin, Evgeny


    N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we describe synthesis of short peptides, containing a new building block-N-amidino-pyroglutamic acid. Although direct guanidinylation of pyroglutamic acid and oxidation of N-amidino-proline using RuO(4) did not produce positive results, N-amidino-Glp-Phe-OH was synthesized on Wang polymer by cyclization of alpha-guanidinoglutaric acid residue. In the course of synthesis, it was found that literature procedure of selective Boc deprotection using TMSOTf/TEA reagent is accompanied by concomitant side reaction of triethylamine alkylation by polymer linker fragment. It should be mentioned that independently from cyclization time and coupling agent (DIC or HCTU), the lactam formation was incomplete. Separation of the cyclic product from the linear precursor was achieved by HPLC in ammonium formate buffer at pH 6. HPLC analysis showed N-amidino-Glp-Phe-OH stability at acidic and physiological pH and fast ring opening in water solution at pH 9. The suggested method of N-amidino-Glp residue formation can be applied in the case of short peptide chains, whereas synthesis of longer ones will require fragment condensation approach.

  1. Radiolytic cyclization of stem-and-loop structured oligodeoxynucleotide with neighboring arrangement of α,ω-bis-disulfides. (United States)

    Tanabe, Kazuhito; Matsumoto, Eiji; Ito, Takeo; Nishimoto, Sei-ichi


    Upon X-ray irradiation of hypoxic aqueous solution, modified oligodeoxynucleotides (ODNs) bearing a pair of disulfides at both ends of the strand that forms a stem-and-loop structure with a neighboring arrangement of α,ω-bis-disulfides underwent efficient cyclization via an intramolecular exchange reaction at the disulfide moieties with a multiple turnover process. Mechanistic studies revealed that hydrogen atoms generated in the radiolysis of water are key active species initiating a chain reaction to produce cyclic ODN disulfides, in which addition of hydrogen atom results in dissociation of the original disulfide bond to generate a thiyl radical intermediate as the chain carrier for the succeeding disulfide exchange into cyclization. The properties were also assessed for the resultant cyclic ODN disulfide that has several favorable features for use in the transcriptional decoy strategy. The cyclic ODN disulfides produced by the present radiolytic method showed high thermal stability, resistance to nuclease, and high binding activity to a representative transcriptional factor of nuclear factor κB.

  2. Synthesis and crystal structure of 3-(4‧-nitrophenyl)iminocoumarin, and cyclization reaction mechanism based on DFT calculation (United States)

    Zhang, Chao-Zhi; Li, Shi-Juan; Cao, Hui; Song, Ming-Xia; Kong, Qing-Gang


    A convenient method was reported to synthesize 3-(4‧-nitrophenyl)iminocoumarin by a cyclization reaction following a Knoevenagel reaction of 2-hydroxybenzaldehyde with 4-nitrophenylacenitrile in an ethanol solution. Piperidine or piperazine was employed respectively as catalyst. Crystal structure of 3-(4‧-nitrophenyl)iminocoumarin shows that the molecules are H-aggregation due to π-π stacking and hydrogen bonds between adjacent molecules, as a result, electrons would transfer easily from a molecule to an adjacent molecule. Based on theoretical calculations of the electronic structures and thermodynamic parameters of the reactive intermediates in these cyclization reactions, the reaction mechanisms were postulated. Data of single crystal and spectrum of UV-vis absorption show that 3-(4‧-nitrophenyl)iminocoumarin is good π-conjugated compound and would be potentially employed as donor-acceptor polymer units for developing bulk heterojunction solar cell. This paper suggests a convenient and effective method for synthesizing ring-locked D-A copolymer units for developing solar cell materials.

  3. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: outcomes for genetic screening techniques. (United States)

    Petříčková, Kateřina; Chroňáková, Alica; Zelenka, Tomáš; Chrudimský, Tomáš; Pospíšil, Stanislav; Petříček, Miroslav; Krištůfek, Václav


    A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products) in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike "classical" primary metabolism ALAS, the C5N unit-forming cyclizing ALAS (cALAS) catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of "classical" ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87% putatively encoding cALAS. Phylogenetic analysis of the hemA homologs revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GenBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  4. Intein-mediated backbone cyclization of VP1 protein enhanced protection of CVB3-induced viral myocarditis (United States)

    Qi, Xingmei; Xiong, Sidong


    CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E. coli. As a result, the cyclic VP1 was significantly more stable against irreversible aggregation upon heating and against carboxypeptidase in vitro and the degradation rate was more slowly in vivo. Compared with linear VP1, immunization mice with circular VP1 significantly increased CVB3-specific serum IgG level and augmented CVB3-specific cellular immune responses, consequently afforded better protection against CVB3-induced viral myocarditis. The cyclic VP1 may be a novel candidate protein vaccine for preventing CVB3 infection and similar approaches could be employed to a variety of protein vaccines to enhance their protection effect. PMID:28148910

  5. Alcohol Dependence and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Karl Mann


    Full Text Available Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of alcoholic liver disease (ALD is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE has significantly improved the early diagnosis of alcoholic liver cirrhosis (ALC. As demonstrated in the literature, inflammation-associated liver stiffness (LS rapidly decreases during alcohol detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of nalmefene in reducing alcohol consumption. Patients with a high or very high drinking risk level (DRL at baseline and randomisation show a clinically significant effect from nalmefene treatment, which is generally well tolerated. Moreover, reduced alcohol consumption supported by nalmefene in combination with psychosocial support may indeed help to reduce the alcohol-related burden and the large treatment gap.

  6. Allyl/propenyl phenol synthases from the creosote bush and engineering production of specialty/commodity chemicals, eugenol/isoeugenol, in Escherichia coli. (United States)

    Kim, Sung-Jin; Vassão, Daniel G; Moinuddin, Syed G A; Bedgar, Diana L; Davin, Laurence B; Lewis, Norman G


    The creosote bush (Larrea tridentata) harbors members of the monolignol acyltransferase, allylphenol synthase, and propenylphenol synthase gene families, whose products together are able to catalyze distinct regiospecific conversions of various monolignols into their corresponding allyl- and propenyl-phenols, respectively. In this study, co-expression of a monolignol acyltransferase with either substrate versatile allylphenol or propenylphenol synthases in Escherichia coli established that various monolignol substrates were efficiently converted into their corresponding allyl/propenyl phenols, as well as providing proof of concept for efficacious conversion in a bacterial platform. This capability thus potentially provides an alternate source to these important plant phytochemicals, whether for flavor/fragrance and fine chemicals, or ultimately as commodities, e.g., for renewable energy or other intermediate chemical purposes. Previous reports had indicated that specific and highly conserved amino acid residues 84 (Phe or Val) and 87 (Ile or Tyr) of two highly homologous allyl/propenyl phenol synthases (circa 96% identity) from a Clarkia species mainly dictate their distinct regiospecific catalyzed conversions to afford either allyl- or propenyl-phenols, respectively. However, several other allyl/propenyl phenol synthase homologs isolated by us have established that the two corresponding amino acid 84 and 87 residues are not, in fact, conserved.

  7. Alcohol homograph priming in alcohol-dependent inpatients

    NARCIS (Netherlands)

    Woud, M.L.; Salemink, E.; Gladwin, T.E.; Wiers, R.W.H.J.; Becker, E.S.; Lindenmeyer, J.; Rinck, M.


    Aim: Alcohol dependency is characterized by alcohol-related interpretation biases (IBs): Individuals with high levels of alcohol consumption generate more alcohol-related than alcohol-unrelated interpretations in response to ambiguous alcohol-related cues. However, a response bias could be an altern

  8. Alcohol Use and Older Adults (United States)

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  9. Alcohol in moderation

    DEFF Research Database (Denmark)

    Mueller, Simone; Lockshin, Larry; Louviere, Jordan J.


    Purpose: The study examines the market potential for low and very low alcohol wine products under two different tax regimes. The penetration and market share of low alcohol wine are estimated under both tax conditions. Consumers’ alcoholic beverage purchase portfolios are analysed and those...... products identified, which are jointly purchased with low alcohol wines. The effect of a tax increase on substitution patterns between alcoholic beverages is examined. Methodology: In a discrete choice experiment, based on their last purchase, consumers select one or several different alcoholic beverages...... volume is estimated under the current tax regime. Between six to eight percent of consumers are expected to adopt low alcohol wine alternatives as part of their alcoholic beverage portfolio. Consumers of cask wine and light beer are more likely and consumers of medium-full strength beer and spirits...

  10. Myths about drinking alcohol (United States)

    ... gov/ency/patientinstructions/000856.htm Myths about drinking alcohol To use the sharing features on this page, ... We know much more about the effects of alcohol today than in the past. Yet, myths remain ...

  11. Benzyl Alcohol Topical (United States)

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  12. Alcohol Use Screening (United States)

    ... Centers Diseases + Condition Centers Mental Health Medical Library Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  13. Women and Alcohol (United States)

    ... turn JavaScript on. Feature: Rethinking Drinking Women and Alcohol Past Issues / Spring 2014 Table of Contents Women react differently than men to alcohol and face higher risks from it. Pound for ...

  14. Alcohol Facts and Statistics (United States)

    ... Standard Drink? Drinking Levels Defined Alcohol Facts and Statistics Print version Alcohol Use in the United States: ... 1245, 2004. PMID: 15010446 11 National Center for Statistics and Analysis. 2014 Crash Data Key Findings (Traffic ...

  15. Children of alcoholics

    Directory of Open Access Journals (Sweden)

    Robert Oravecz


    Full Text Available The author briefly interprets the research – results, referring to the phenomenon of children of alcoholics, especially the psychological and psychopathological characteristics of children of alcoholics in adolescence and young adulthood. The author presents a screening study of adolescents. The sample contains 200 high school students at age 18. The aim of the survey was to discover the relationship between alcohol consumption of parents, PTSD - related psychopathological symptoms and reported life quality of their children. The study confirmed the hypothesis about a substantial correlation between high alcohol consumption of parents, higher psychopathological symptom - expression and lower reported life quality score of their children. Higher PTSD-related symptomatology in children of alcoholics is probably resulted by home violence, which is very often present in family of alcoholics. The article also evaluated the results regarding suicide ideation of children of alcoholics, which is definitely more frequent and more intense than in their peers living in non alcohol – dependent families.

  16. Alcohol and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Gao Yinglan; Song Jingyu; Jin Junshuo; Zhong Xiuhong; Ren Xiangshan; Liu Shuangping


    Objectives To study the relationship between alcohol and atherosclerosis (AS).Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS.Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis,which could lead to AS.

  17. Synthetic Study of Dragmacidin E: Construction of the Core Structure Using Pd-Catalyzed Cascade Cyclization and Rh-Catalyzed Aminoacetoxylation. (United States)

    Inoue, Naoya; Nakano, Shun-Ichi; Harada, Shingo; Hamada, Yasumasa; Nemoto, Tetsuhiro


    We developed a novel synthetic method of the core structure of dragmacidin E bearing a 7-membered ring-fused bis(indolyl)pyrazinone skeleton. Formation of the 7-membered ring-fused tricyclic indole skeleton was accomplished using a palladium-catalyzed Heck insertion-allylic amination cascade. Vicinal difunctionalization of the 7-membered ring was realized via a rhodium-catalyzed aminoacetoxylation.

  18. S-Allyl-Cysteines Reduce Amelioration of Aluminum Induced Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Sadhana Shrivastava


    Full Text Available Problem statement: Aluminum (Al is a trivalent cation found in its ionic form in most kinds of animal tissues and in natural waters everywhere. Approach: It is a potent neurotoxin and has been associated in the pathogenesis of several clinical disorders including Alzheimer’s disease. Results: The aim of the study was to demonstrate the protective effect of S-Allyl-Cysteines (SAC against Al-induced toxicity in rat model on certain biochemical parameters, lipid peroxidation and oxidative stress enzymes of white albino rats. Six rats per group were divided into various treatment groups. Group one rats were given normal saline and served as control group. Group two animals received Al as aluminum nitrate 32.5 mg (i.p. for the induction of toxicity. Group three to five received different doses of SAC (25, 50 and 100 mg kg-1 for 3 days after 24 h of Al toxicity. Rats were orally administered their respective doses every day for 3 days. Evaluations were made in blood and tissues. The activity of Acetylcholinesterase (AchE was inhibited in all the parts of brain after Al intoxication. Significant rise were observed the Activities of Serum Transaminases (AST and ALT after toxicant exposure. The activity of â-Aminolevulinic acid Dehydratase (ALAD in blood and â-Aminolevulinic Acid Synthetase (ALAS in brain was decreased after Al exposure. Al significant increased cholesterol, triglyceride, creatinine and urea level in serum. TBARS level was significantly higher and GSH content were significantly lower during toxicity. Total and esterified cholesterol in liver, kidney and brain were increased after Al exposure. Histopathological changes in liver, kidney and brain were also recouped with the therapy. Conclusion/Recommendations: Our data proved that SAC which is a bioactive and bioavailable component of garlic has organosulfur compounds which regulates the thiol status of the cell and scavenges free radicals and work as an antioxidant. Thus SAC

  19. New copolymer of acrylamide with allyl methacrylate and its capacity for the removal of azo dyes

    Directory of Open Access Journals (Sweden)

    Yeliz Yildirim


    Full Text Available The copolymerization reactions of Acrylamide (AA with the different mole ratios of allyl methacrylate (AMA such as 25/75, 50/50 and 75/25 were studied by radical polymerization under argon atmosphere using 2,2’-Azobis (isobutyronitri1e (AIBN as initiator. The copolymers were characterized with Fourier transform infrared spectroscopy (FTIR and thermogravimetric analysis (TG. FTIR spectra showed that the C=O, C-N and N-H groups in copolymers remained during the copolymerization. It is concluded from the thermograms that Poly(AA-co-AMA copolymers which contained different ratios of monomer and comonomer exhibit similar thermal behavior. Adsorption capacity, kinetic and isotherm studies of Direct Brown 2 onto the copolymers have been evaluated. Different factors such as the monomer ratio, pH, initial dye concentration, copolymer dosage and contact time affecting the removal process were studied. It was found that the adsorption process agreed with the Freundlich and Dubinin-Raduskevich model and the adsorption of Direct Brown 2 depended on the acrylamide content and pH of the solution. The standard Gibb’s free energy was determined as - 14.7 kJ/mol, which means that adsorption occurred spontaneously and the process is feasible. Increasing the acrylamide content led to increased adsorption of Direct Brown 2 on the copolymer. Moreover, adsorption kinetic studies showed that the adsorption followed a pseudo-second-order kinetic model, indicating that the chemical adsorption was the rate-limiting step. These results show that Poly(AA-co-AMA can be used as adsorbent for water pollutants such as Direct Brown 2 and has potential applications in related industrial and environmental areas.

  20. Stereoselective coordination: a six-membered P,N-chelate tailored for asymmetric allylic alkylation. (United States)

    Császár, Z; Farkas, G; Bényei, A; Lendvay, G; Tóth, I; Bakos, J


    Six-membered chelate complexes [Pd(1a-b)Cl2], (2a-b) and [Pd(1a-b)(η(3)-PhCHCHCHPh)]BF4, (3a-b) of P,N-type ligands 1a, ((2S,4S)-2-diphenyl-phosphino-4-isopropylamino-pentane) and 1b, ((2S,4S)-2-diphenyl-phosphino-4-methylamino-pentane) have been prepared. The Pd-complexes have been characterized in solution by 1D and 2D NMR spectroscopy. The observed structures were confirmed by DFT calculations and in the case of 2a also by X-ray crystallography. Unexpectedly, the coordination of the all-carbon-backbone aminophosphine 1a resulted in not only a stereospecific locking of the donor nitrogen atom into one of the two possible configurations but also the conformation of the six-membered chelate rings containing three alkyl substituents was forced into the same single chair structure showing the axially placed isopropyl group on the coordinated N-atom. The stereodiscriminative complexation of 1a led to the formation of a palladium catalyst with a conformationally rigid chelate having a configurationally fixed nitrogen and electronically different coordination sites due to the presence of P and N donors. The stereochemically fixed catalyst provided excellent ee's (up to 96%) and activities in asymmetric allylic alkylation reactions. In contrast, the chelate rings formed by 1b exist in two different chair conformations, both containing axial methyl groups, but with the opposite configurations of the coordinated N-atom. Pd-complexes of 1b provided low enantioselectivities in similar alkylations, therefore emphasizing the importance of the stereoselective coordination of N-atoms in analogous P-N chelates. The factors determining the coordination of the ligands were also studied with respect to the chelate ring conformation and the nitrogen configuration.

  1. Mechanisms of transient receptor potential vanilloid 1 activation and sensitization by allyl isothiocyanate. (United States)

    Gees, Maarten; Alpizar, Yeranddy A; Boonen, Brett; Sanchez, Alicia; Everaerts, Wouter; Segal, Andrei; Xue, Fenqin; Janssens, Annelies; Owsianik, Grzegorz; Nilius, Bernd; Voets, Thomas; Talavera, Karel


    Allyl isothiocyanate (AITC; aka, mustard oil) is a powerful irritant produced by Brassica plants as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is widely used experimentally as an inducer of acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 (TRPV1). Although it is generally accepted that electrophilic agents activate these channels through covalent modification of cytosolic cysteine residues, the mechanism underlying TRPV1 activation by AITC remains unknown. Here we show that, surprisingly, AITC-induced activation of TRPV1 does not require interaction with cysteine residues, but is largely dependent on S513, a residue that is involved in capsaicin binding. Furthermore, AITC acts in a membrane-delimited manner and induces a shift of the voltage dependence of activation toward negative voltages, which is reminiscent of capsaicin effects. These data indicate that AITC acts through reversible interactions with the capsaicin binding site. In addition, we show that TRPV1 is a locus for cross-sensitization between AITC and acidosis in nociceptive neurons. Furthermore, we show that residue F660, which is known to determine the stimulation by low pH in human TRPV1, is also essential for the cross-sensitization of the effects of AITC and low pH. Taken together, these findings demonstrate that not all reactive electrophiles stimulate TRPV1 via cysteine modification and help understanding the molecular bases underlying the surprisingly large role of this channel as mediator of the algesic properties of AITC.

  2. Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

    Directory of Open Access Journals (Sweden)

    Verena Weidmann


    Full Text Available Allylic oxidations of olefins to enones allow the efficient synthesis of value-added products from simple olefinic precursors like terpenes or terpenoids. Biocatalytic variants have a large potential for industrial applications, particularly in the pharmaceutical and food industry. Herein we report efficient biocatalytic allylic oxidations of spirocyclic terpenoids by a lyophilisate of the edible fungus Pleurotus sapidus. This ‘’mushroom catalysis’’ is operationally simple and allows the conversion of various unsaturated spirocyclic terpenoids. A number of new spirocyclic enones have thus been obtained with good regio- and chemoselectivity and chiral separation protocols for enantiomeric mixtures have been developed. The oxidations follow a radical mechanism and the regioselectivity of the reaction is mainly determined by bond-dissociation energies of the available allylic CH-bonds and steric accessibility of the oxidation site.

  3. Rh(III)- and Zn(II)-Catalyzed Synthesis of Quinazoline N-Oxides via C-H Amidation-Cyclization of Oximes. (United States)

    Wang, Qiang; Wang, Fen; Yang, Xifa; Zhou, Xukai; Li, Xingwei


    Quinazoline N-oxides have been prepared from simple ketoximes and 1,4,2-dioxazol-5-ones via Rh(III)-catalyzed C-H activation-amidation of the ketoximes and subsequent Zn(II)-catalyzed cyclization. The substrate scope and functional group compatibility were examined. The reaction features relay catalysis by Rh(III) and Zn(II).

  4. Cyclic pentapeptide analogs based on endomorphin-2 structure: cyclization studies using liquid chromatography combined with on-line mass spectrometry and tandem mass spectrometry. (United States)

    Piekielna, Justyna; Kluczyk, Alicja; Perlikowska, Renata; Janecka, Anna


    The cyclization of linear analogs based on endomorphin-2 structure, Tyr/Dmt-d-Lys-Phe-Phe-Asp-NH2 and Tyr/Dmt-d-Cys-Phe-Phe-Cys-NH2 (where Dmt=2',6'-dimethyltyrosine), resulting in obtaining lactam or disulfide derivatives, was studied using liquid chromatography combined with on-line mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). In case of cyclization via an amide bond, the formation of the cyclic monomers, cyclic but not linear dimers and even traces of cyclic trimers was observed. Disulfide bridge containing peptides was obtained by the solid-phase synthesis of the linear sequences, followed by either in-solution or on-resin cyclization. In case of the in-solution cyclization, the expected cyclic monomers were the only products. When oxidation of the cysteine residues was performed when the peptides were still on the resin, cyclic monomer and two cyclodimers, parallel and antiparallel, were found. Digestion of the isolated cyclodimers with α-chymotrypsin allowed for their unambiguous identification. The comparison of the cyclic monomer/dimer ratios for analogs with Tyr versus Dmt in position 1 revealed that the presence of the exocyclic Dmt favored formation of the cyclic monomer, most likely due to the increased steric bulk of this amino acid side-chain as compared with Tyr.

  5. Highly regioselective synthesis of dicyano-8a, 10,11-trihydropyrrolo [1,2-a][1,10]phenanthrolines via a domino-Knoevenagel-cyclization

    Institute of Scientific and Technical Information of China (English)

    Reza heydari; Batool Tahamipour


    1,10-Phenanthrolinium N-ylides, can react with malonitrile and aromatic aldehydes via a domino-Knoevenagel cyclization to afford a new class of mhydropyrrolo[l,2-a][l,10]phenanthroline derivatives as stable helical compounds in a simple, mild, and efficient protocol in excellent yields.

  6. PtCl2-catalyzed tandem enyne cyclization/1,2 ester migration reaction controlled by substituent effects of all-carbon 1,6-enynyl esters. (United States)

    Huo, Xing; Zhao, Changgui; Zhao, Gaoyuan; Tang, Shouchu; Li, Huilin; Xie, Xingang; She, Xuegong


    On the move: A novel PtCl2-catalyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration reaction was developed, which was shown to be controlled by substitution effects. Using this method, a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields.

  7. Rheological and mechanical behavior of polyacrylamide hydrogels chemically crosslinked with allyl agarose for two-dimensional gel electrophoresis. (United States)

    Suriano, R; Griffini, G; Chiari, M; Levi, M; Turri, S


    Two-dimensional (2-D) gel electrophoresis currently represents one of the most standard techniques for protein separation. In addition to the most commonly employed polyacrylamide crosslinked hydrogels, acrylamide-agarose copolymers have been proposed as promising systems for separation matrices in 2-D electrophoresis, because of the good resolution of both high and low molecular mass proteins made possible by careful control and optimization of the hydrogel pore structure. As a matter of fact, a thorough understanding of the nature of the hydrogel pore structure as well as of the parameters by which it is influenced is crucial for the design of hydrogel systems with optimal sieving properties. In this work, a series of acrylamide-based hydrogels covalently crosslinked with different concentrations of allyl agarose (0.2-1%) is prepared and characterized by creep-recovery measurements, dynamic rheology and tensile tests, in the attempt to gain a clearer understanding of structure-property relationships in crosslinked polyacrylamide-based hydrogels. The rheological and mechanical properties of crosslinked acrylamide-agarose hydrogels are found to be greatly affected by crosslinker concentration. Dynamic rheological tests show that hydrogels with a percentage of allyl agarose between 0.2% and 0.6% have a low density of elastically effective crosslinks, explaining the good separation of high molecular mass proteins in 2-D gel electrophoresis. Over the same range of crosslinker concentration, creep-recovery measurements reveal the presence of non-permanent crosslinks in the hydrogel network that justifies the good resolution of low molecular mass proteins as well. In tensile tests, the hydrogel crosslinked with 0.4% of allyl agarose exhibits the best results in terms of mechanical strength and toughness. Our results show how the control of the viscoelastic and the mechanical properties of these materials allow the design of mechanically stable hydrogels with improved

  8. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna


    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  9. Alcoholism and Lesbians (United States)

    Gedro, Julie


    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  10. Television: Alcohol's Vast Adland. (United States)


    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  11. Hispanic Alcoholic Treatment Considerations. (United States)

    Costello, Raymond M.


    A path analytic model for Hispanic alcoholics relating socioclinical prognostic variables to outcome following treatment in a therapeutic community differs markedly from that fitted to Anglo alcoholics. The differential relationship of education to alcoholism severity and outcome was noted specifically as reflecting different racial-ethnic paths…

  12. Fetal Alcohol Exposure (United States)

    ... her child’s genetic make-up, and changes in gene activity caused by prenatal alcohol exposure. NIH . . . Turning Discovery Into Health ® National Institute on Alcohol Abuse and Alcoholism www. niaaa. nih. gov • 301.443.3860 Interventions ...

  13. Alcohol and Minority Youth. (United States)

    Wright, Roosevelt, Jr.; Watts, Thomas D.


    Maintains that minority youth who use (or abuse) alcohol in American society deal with using alcohol, being minority, and being young, three dimensions viewed by society with mixed, sometimes hostile and/or fearful reactions. Suggests that examining alcoholism among minority youth involves coming to grips with poverty, education, income, and life…

  14. Pressure-Resistant Plane Disc Viewports from Allyl Diglycol Carbonate Plastic for Hyperbaric Chambers. (United States)


    DISINFECTANT DEPTH OF CRAZING, in. STCP*, psi 6blu Vii-o-Ter 0.129 250 6b2u Lysol 0.159 220 6b3u methyl alcohol 0.184 120 6b4u Staphene 0.126 300 6b5u Amphyl...FOR 60 MIN SPECIMEN NO. DISINFECTANT DEPTH CRAZING, in. STCP*, psi 6alc Viro-Tec 0.117 270 6a2c Lysol failed after 18.5 min 6a3c methyl alcohol

  15. Antimicrobial activity of allyl isothiocyanate used to coat biodegradable composite films as affected by storage and handling conditions. (United States)

    Li, Weili; Liu, Linshu; Jin, Tony Z


    We evaluated the effects of storage and handling conditions on the antimicrobial activity of biodegradable composite films (polylactic acid and sugar beet pulp) coated with allyl isothiocyanate (AIT). Polylactic acid and chitosan were incorporated with AIT and used to coat one side of the film. The films were subjected to different storage conditions (storage time, storage temperature, and packed or unpacked) and handling conditions (washing, abrasion, and air blowing), and the antimicrobial activity of the films against Salmonella Stanley in tryptic soy broth was determined. The films (8.16 μl of AIT per cm(2) of surface area) significantly (P packaging.


    Institute of Scientific and Technical Information of China (English)

    陈春武; 谢令德; 陈雅群; 何君; 贺艳萍


    以玉米象和赤拟谷盗作为实验对象,采用熏蒸方式对烯丙基异硫氰酸酯的毒力进行测定.结果表明,烯丙基异硫氰酸酯对所研究的两种害虫有较好的快速致死作用,同时研究发现在相同熏蒸时间内烯丙基异硫氰酸酯对玉米象熏蒸的LC50和LC99均小于对赤拟谷盗的LC50和LC99,这说明烯丙基异硫氰酸酯对玉米象的熏蒸效果比对赤拟谷盗的好.%Chosing Si tophilus zesmais (Motschulsky) and Tribolium castaneun (Herbst) as experimental objects, the toxicity for the allyl isothiocyanate (AITC) is tested systematically by fumigation method. The result demonstrates that the allyl isothiocyanate presents rapid lethal effect against both of the two types of insects. The research also shows that both the LC50 and the LC99 of the fumigation of the allyl isothiocyanate to the Sitophilus zeamais are less than those of the allyl isothiocyanate to the Tribolium castaneum exposuring the same fumigating time, which indicates that the fumigating effect of the allyl isothiocyanate to the Sitophilus zeamais is more effective than that of the allyl isothiocyanate to the Tribolium castaneum.

  17. [bmim][Br] as a solvent and activator for the Ga-mediated Barbier allylation: direct formation of an N-heterocyclic carbene from Ga metal. (United States)

    Goswami, Dibakar; Chattopadhyay, Angshuman; Sharma, Anubha; Chattopadhyay, Subrata


    The room-temperature ionic liquid (RTIL) [bmim][Br] has been found to be an excellent green and inexpensive medium for the Ga-mediated allylation of aromatic and aliphatic aldehydes and ketones. The RTIL activated the metal via formation of a Ga-N-heterocyclic carbene complex that assisted in the completion of the reaction at ambient temperature with only 0.5 equiv of Ga and 1.2 equiv of allyl bromide with respect to the carbonyl substrates. The present protocol required a much shorter time than those reported in the literature using other metals and solvents and proceeded with good yields and excellent selectivity.

  18. Synthesis, Characterization, and In Vitro Evaluation of New (99m)Tc/Re(V)-Cyclized Octreotide Analogues: An Experimental and Computational Approach. (United States)

    Li, Yawen; Ma, Lixin; Gaddam, Vikram; Gallazzi, Fabio; Hennkens, Heather M; Harmata, Michael; Lewis, Michael R; Deakyne, Carol A; Jurisson, Silvia S


    Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing (186)Re- and (188)Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe(1)-Cys(2)-Tyr(3)-DTrp(4)-Lys(5)-Thr(6)-Cys(7)-Thr(OH)(8) (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO](3+) core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys(2) in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr(3) in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO](3+) core. The re-cyclization reaction was translated to the (99m)Tc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total (99m)Tc labeling yield was achieved by ligand exchange from (99m)Tc-glucoheptonate at 60 °C for an hour. About 100% and 51% of (99m)Tc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.

  19. Close correlation between heat shock response and cytotoxicity in Neurospora crassa treated with aliphatic alcohols and phenols

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, U.; Schweim, P.; Fracella, F.; Rensing, L. [Univ. of Bremen (Germany)


    In Neurospora crassa the aliphatic alcohols methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, ethylene glycol, glycerol, and allyl alcohol and the phenolic compounds phenol, hydroquinone, resorcinol, pyrogallol, phloroglucinol, sodium salicylate, and acetylsalicylic acid were analyzed with respect to their capacities to induce heat shock proteins (HSP) and to inhibit protein synthesis. Both the alcohols and phenols showed the greatest levels of HSP induction at concentrations which inhibited the overall protein synthesis by about 50%. The abilities of the different alcohols to induce the heat shock response are proportional to their lipophilicities: the lipophilic alcohol isobutanol is maximally inductive at about 0.6 M, whereas the least lipophilic alcohol, methanol, causes maximal induction at 5.7 M. The phenols, in general, show a higher capability to induce the heat shock response. The concentrations for maximal induction range between 25 mM (sodium salicylate) and 100 mM (resorcinol). Glycerol (4.1 M) shifted the concentration necessary for maximal HSP induction by hydroquinone from 50 to 200 mM. The results reveal that the induction of HSP occurs under conditions which considerably constrain cell metabolism. The heat shock response, therefore, does not represent a sensitive marker for toxicity tests but provides a good estimate for the extent of cell damage.

  20. Genetics and alcoholism. (United States)

    Edenberg, Howard J; Foroud, Tatiana


    Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

  1. [Physical diseases in alcoholism]. (United States)

    Takase, Kojiro


    Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life.

  2. Oxidative Cyclization of Sulfamate Esters Using NaOCl - A Metal-Mediated Hoffman-Löffler Freytag Reaction. (United States)

    Zalatan, David N; Du Bois, J


    Intramolecular C-H amination with sulfamate esters occurs under the action of dinuclear Rh catalysts and iodine(III) oxidants, and has recently emerged as a powerful tool for synthesis. Insights gained through mechanistic studies of this process suggest that other terminal oxidants, including common halogenating agents such as NaOCl, could function to promote the cyclization reaction. Results described in this report demonstrate that the combination of NaOCl and 3 mol% Rh(2)(oct)(4) is effective in select cases for converting sulfamate substrates to the corresponding [1,2,3]-oxathiazinane-2,2-dioxide heterocycles. The mechanism for C-H functionalization, however, is distinct from that induced by hypervalent iodine reagents and likely involves the intermediacy of an N-centered radical.

  3. Oxidative Cyclization of Sulfamate Esters Using NaOCl – A Metal-Mediated Hoffman-Löffler Freytag Reaction (United States)

    Zalatan, David N.; Du Bois, J.


    Intramolecular C–H amination with sulfamate esters occurs under the action of dinuclear Rh catalysts and iodine(III) oxidants, and has recently emerged as a powerful tool for synthesis. Insights gained through mechanistic studies of this process suggest that other terminal oxidants, including common halogenating agents such as NaOCl, could function to promote the cyclization reaction. Results described in this report demonstrate that the combination of NaOCl and 3 mol% Rh2(oct)4 is effective in select cases for converting sulfamate substrates to the corresponding [1,2,3]-oxathiazinane-2,2-dioxide heterocycles. The mechanism for C–H functionalization, however, is distinct from that induced by hypervalent iodine reagents and likely involves the intermediacy of an N-centered radical. PMID:19319207

  4. Giffonins J-P, Highly Hydroxylated Cyclized Diarylheptanoids from the Leaves of Corylus avellana Cultivar "Tonda di Giffoni". (United States)

    Masullo, Milena; Cantone, Vincenza; Cerulli, Antonietta; Lauro, Gianluigi; Messano, Francesco; Russo, Gian Luigi; Pizza, Cosimo; Bifulco, Giuseppe; Piacente, Sonia


    Two new diaryl ether heptanoids, giffonins J and K (1 and 2), along with five new diarylheptanoids, giffonins L-P (3-7), were isolated from a methanol extract of the leaves of Corylus avellana cultivar "Tonda di Giffoni". These compounds were identified as highly hydroxylated cyclized diarylheptanoids by 1D- and 2D-NMR experiments. The relative configurations of giffonins J-P (1-7) were established by a combined QM (quantum mechanical)/NMR approach, comparing the experimental (13)C/(1)H NMR chemical shift data and the related predicted values. The cytotoxic activities of giffonins J-P (1-7) were evaluated against the human osteosarcoma U2Os and SAOs cell lines.

  5. Alcohol disrupts sleep homeostasis. (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep


    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  6. From adjacent activation in E. coli and DNA cyclization to eukaryotic enhancers : the elements of a puzzle.

    Directory of Open Access Journals (Sweden)

    Michèle eAMOUYAL


    Full Text Available DNA cyclization, E. coli lac repressor binding to two spaced lac operators and repression enhancement can be successfully used for a better understanding of the conditions required for interaction between eukaryotic enhancers and the machinery of transcription initiation. Chronologically, the DNA looping model has first accounted for the properties initially defining enhancers, i.e. independence of action with distance or orientation with respect to the start of transcription. It has also predicted enhancer activity or its disruption at short distance (site orientation, alignment between promoter and enhancer sites, with high-order complexes of protein, or with transcription factor concentrations close or different from the w.t. situation. In another step, histones have been introduced into the model to further adapt it to eukaryotes. They in fact favor DNA cyclization in vitro. The resulting DNA compaction might explain the difference counted in base pairs in the distance of action between eukaryotic transcription enhancers and prokaryotic repression enhancers. The lac looping system provides a potential tool for analysis of this discrepancy and of chromatin state directly in situ. Furthermore, as predicted by the model, the contribution of operators O2 and O3 to repression of the lac operon clearly depends on the lac repressor level in the cell and is prevented in strains overproducing lac repressor. By extension, gene regulation especially that linked to cell fate, should also depend on transcription factor levels, providing a potential tool for cellular therapy. In parallel, a new function of the O1-O3 loop completes the picture of lac repression. The O1-O3 loop would at the same time ensure high efficiency of repression, inducibility through the low-affinity sites and limitation of the level of repressor through self-repression of the lac repressor. Last, the DNA looping model can be successfully adapted to the enhancer auxiliary elements

  7. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: Outcomes for genetic screening techniques

    Directory of Open Access Journals (Sweden)

    Katerina ePetrickova


    Full Text Available A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike classical primary metabolism ALAS, the C5N unit-forming cALAS (cyclizing ALAS catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of classical ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87 % putatively encoding cALAS. Phylogenetic analysis of the hemA homologues revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GeneBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  8. Molecular detection and in vitro antioxidant activity of S-allyl-L-cysteine (SAC) extracted from Allium sativum. (United States)

    Sun, Y-E; Wang, W-D


    It is well known that Allium sativum has potential applications to clinical treatment of various cancers due to its remarkable ability in eliminating free radicals and increasing metabolism. An allyl-substituted cysteine derivative - S-allyl-L-cysteine (SAC) was separated and identified from Allium sativum. The extracted SAC was reacted with 1-pyrenemethanol to obtain pyrene-labelled SAC (Py-SAC) to give SAC fluorescence properties. Molecular detection of Py-SAC was conducted by steady-state fluorescence spectroscopy and time-resolved fluorescence method to quantitatively measure concentrations of Py-SAC solutions. The ability of removing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical using Py-SAC was determined through oxygen radical absorbance capacity (ORAC). Results showed the activity of Py-SAC and Vitamin C (VC) with ORAC as index, the concentrations of Py-SAC and VC were 58.43 mg/L and 5.72 mg/L respectively to scavenge DPPH, and 8.16 mg/L and 1.67 mg/L to scavenge •OH respectively. Compared with VC, the clearance rates of Py-SAC to scavenge DPPH were much higher, Py-SAC could inhibit hydroxyl radical. The ability of removing radical showed a dose-dependent relationship within the scope of the drug concentration.

  9. The - - and Submm-Wave Spectrum of Allyl Isocyanide and Radioastronomical Observations in Orion KL and the Primos Line Survey (United States)

    Haykal, I.; Motiyenko, R. A.; Margules, L.; Huet, T. R.; Ecija, P.; Cocinero, E. J.; Basterretxea, F.; Fernandez, J. A.; Castano, F.; Tercero, B.; Cernicharo, J.; Lesarri, A.; Guillemin, J. C.


    Last year we presented the first rotational analysis of the ground state of the two conformers of allyl isocyanide from 4 GHz to 905 GHz. The analysis of the rotational spectrum of the cis conformer of allyl isocyanide was extended. We resolved Coriolis interactions of a and b types between the excited vibrational states ν_1=1 and ν_2=1, calculated to be at 156 cm^{-1} (A^{'}) and 167 cm^{-1} (A^{''}) respectively (MP2/aug-cc-pvtz), from 150 GHz to 600 GHz. Strong perturbations were observed in the 150-310 GHz range for low values of the quantum number K_a starting from K_a = 0, 1. The anharmonicities appeared as well at higher frequencies for larger quantum numbers. The two modes were fitted together with the SPFIT/SPCAT suite of programs and a set of Coriolis parameters was accurately determined. The fit contains more than 3000 lines up to J = 99 and K_a = 12 for both modes. We did not detect these species neither in the IRAM 30-m line survey of Orion KL nor in the PRIMOS survey towards SgrB2. Nevertheless, we provided upper limits to their column density in Orion KL. This work was supported by the CNES and the Action sur Projets de l'INSU, PCMI. I. Haykal et al. manuscript in preparation H. Pickett J. Mol. Spec.{148}, 371-377, 1991.

  10. Comparative Studies on Conventional and Ultrasound-Assisted Synthesis of Novel Homoallylic Alcohol Derivatives Linked to Sulfonyl Dibenzene Moiety in Aqueous Media

    Directory of Open Access Journals (Sweden)

    Mohamed F. Mady


    Full Text Available Novel homoallylic alcohols incorporating sulfone moieties were synthesized by the treatment of different carbonyl compounds with allylic bromides in aqueous media via sonochemical Barbier-type reaction conditions. Sulfonation of α-bromoketones with sodium benzenesulfinate in presence of CuI/2,6-lutidine rapidly gave β-keto-sulfones in good yields. In general, ultrasound irradiation offered the advantages of high yields, short reaction times, and simplicity compared to the conventional methods. The structures of all the compounds were confirmed by analytical and spectral data.

  11. Microwave-assisted efficient synthesis of 2-arylbenzo[b]furans and 2-ferrocenylbenzo[b]furans from readily prepared propargylic alcohols and -iodophenols

    Indian Academy of Sciences (India)

    Liansheng Wu; Xiaokang Shi; Xiaoyun Xu; Fen Liang; Guosheng Huang


    A simple, efficient and expeditious method for synthesis of 2-arylbenzo[b]furans and 2-ferrocenylbenzo[b]furans from readily prepared propargylic alcohols, -iodophenols and silica gel with the catalyst of PdCl2(PPh3)2 (2 mol%)/CuI (2mol%) and microwave-promoted Sonogashira coupling/cyclization reaction is developed. The methodology can produce good to excellent yields. In addition, this method can also be completed in one-pot with iodobenzene, 2-methyl-3-butyn-2-ol and 2-iodo-4-methylphenol as reactants.

  12. Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

    Energy Technology Data Exchange (ETDEWEB)

    Sávio, André Luiz Ventura, E-mail: [UNESP – Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, Departamento de Patologia, Botucatu, SP (Brazil); Nicioli da Silva, Glenda [UFOP – Universidade Federal de Ouro Preto, Escola de Farmácia, Departamento de Análises Clínicas, Ouro Preto, MG (Brazil); Salvadori, Daisy Maria Fávero [UNESP – Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, Departamento de Patologia, Botucatu, SP (Brazil)


    Highlights: • AITC inhibits mutant and wild-type TP53 cell proliferation. • Morphological changes and cells debris were observed after AITC treatment in both cells. • BAX and BCL2 expression modulation was observed in wild-type TP53 cells. • BCL2, BAX and ANLN increased and S100P decreased expression was detected in mutated TP53 cells. • AITC effects in gene modulation are dependent TP53 gene status. - Abstract: Natural compounds hold great promise for combating antibiotic resistance, the failure to control some diseases, the emergence of new diseases and the toxicity of some contemporary medical products. Allyl isothiocyanate (AITC), which is abundant in cruciferous vegetables and mustard seeds and is commonly referred to as mustard essential oil, exhibits promising antineoplastic activity against bladder cancer, although its mechanism of action is not fully understood. Therefore, the aim of this study was to investigate the effects of AITC activity on bladder cancer cell lines carrying a wild type (wt; RT4) or mutated (T24) TP53 gene. Morphological changes, cell cycle kinetics and CDK1, SMAD4, BAX, BCL2, ANLN and S100P gene expression were evaluated. In both cell lines, treatment with AITC inhibited cell proliferation (at 62.5, 72.5, 82.5 and 92.5 μM AITC) and induced morphological changes, including scattered and elongated cells and cellular debris. Gene expression profiles revealed increased S100P and BAX and decreased BCL2 expression in RT4 cells following AITC treatment. T24 cells displayed increased BCL2, BAX and ANLN and decreased S100P expression. No changes in SMAD4 and CDK1 expression were observed in either cell line. In conclusion, AITC inhibits cell proliferation independent of TP53 status. However, the mechanism of action of AITC differed in the two cell lines; in RT4 cells, it mainly acted via the classical BAX/BCL2 pathway, while in T24 cells, AITC modulated the activities of ANLN (related to cytokinesis) and S100P. These data confirm

  13. Simple and Efficient Ruthenium-Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen. (United States)

    Ray, Ritwika; Chandra, Shubhadeep; Maiti, Debabrata; Lahiri, Goutam Kumar


    Oxidative transformations utilizing molecular oxygen (O2 ) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O2 are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O2 as the "primary" oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium-catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen- or electron-transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including (18) O labeling established the in situ formation of an oxo-ruthenium intermediate as the active catalytic species in the cycle and involvement of a two-electron hydride transfer in the rate-limiting step.

  14. Alcohol and pregnancy

    Directory of Open Access Journals (Sweden)

    Anna Maria Paoletti


    Full Text Available Alcohol exerts teratogenic effects in all the gestation times, with peculiar features in relationship to the trimester of pregnancy in which alcohol is assumed. Alcohol itself and its metabolites modify DNA synthesis, cellular division, cellular migration and the fetal development. The characteristic facies of feto-alcoholic syndrome (FAS-affected baby depends on the alcohol impact on skull facial development during the first trimester of pregnancy. In association there are cerebral damages with a strong defect of brain development up to the life incompatibility. Serious consequences on fetal health also depends on dangerous effects of alcohol exposure in the organogenesis of the heart, the bone, the kidney, sensorial organs, et al. It has been demonstrated that maternal binge drinking is a high factor risk of mental retardation and of delinquent behaviour. Unfortunately, a lower alcohol intake also exerts deleterious effects on fetal health. In several countries of the world there is a high alcohol use, and this habit is increased in the women. Therefore, correct information has to be given to avoid alcohol use by women in the preconceptional time and during the pregnancy. Preliminary results of a study performed by the authors show that over 80% of pregnant and puerperal women are not unaware that more than 2 glasses of alcohol/week ingested during pregnancy can create neurological abnormalities in the fetus. However, after the information provided on alcoholic fetopathy, all women are conscious of the damage caused by the use of alcohol to the fetus during pregnancy. This study confirms the need to provide detailed information on the negative effects of alcohol on fetal health. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  15. Alcohol Expectancies in Young Adult Sons of Alcoholics and Controls. (United States)

    Brown, Sandra A.; And Others

    Adolescent offspring of alcoholics have been found to have higher alcohol reinforcement expectancies than do teenagers from nonalcoholic families. In particular, those with a positive family history of alcoholism expect more cognitive and motor enhancement with alcohol consumption. This study examined the alcohol expectancies of 58 matched pairs…

  16. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Murilo Foppa


    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  17. [Alcohol and nutrition]. (United States)

    Maillot, F; Farad, S; Lamisse, F


    Alcoholism and alcohol-associated organ injury is one of the major health problems worldwide. Alcohol may lead to an alteration in intermediary metabolism and the relation between alcohol intake and body weight is a paradox. The effect of alcohol intake on resting metabolic rate, assessed by indirect calorimetry, and lipid oxidation, is still controversial. Small quantities of ethanol seem to have no effect on body weight. Ingestion of moderate amounts may lead to an increase in body weight, via a lipid-oxidizing suppressive effect. Chronic intake of excessive amounts in alcoholics leads to a decrease in body weight, probably via increased lipid oxidation and energy expenditure. Chronic ethanol abuse alters lipid-soluble (vitamins A, D and E) and water-soluble (B-complex vitamins, vitamin C) vitamins status, and some trace elements status such as magnesium, selenium or zinc.

  18. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim


    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  19. Alcoholism and Diabetes Mellitus


    Soo-Jeong Kim; Dai-Jin Kim


    Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect i...

  20. Alcohol use and menopause. (United States)

    Wilsnack, Richard W; Wilsnack, Sharon C


    Clinicians should periodically assess their menopausal patients' alcohol use. Specific health hazards from excessive alcohol consumption, as well as potential benefits of low-level consumption (for cardiovascular disease, bone health, and type 2 diabetes), should be discussed with their patients who drink. The information in this Practice Pearl can help clinicians provide evidence-based guidance about alcohol consumption and its relationship to common health concerns.

  1. Affordability of alcohol and alcohol-related mortality in Belarus. (United States)

    Razvodovsky, Yury E


    Alcohol abuse has numerous adverse health and social consequences. The consumer response to changes in alcohol affordability is an important issue on alcohol policy debates. Studies from many countries have shown an inverse relationship between alcohol prices and alcohol consumption in the population. There are, however, suggestions that increasing the price of alcohol by rising taxes may have limited effect on alcohol-related problems, associated with long-term heavy drinking. The aim of the present study was to evaluate the relationship between alcohol affordability and alcohol-related mortality rates in post-Soviet Belarus. For this purpose trends in alcohol-related mortality rates (mortality from liver cirrhosis, pancreatitis, alcoholism and alcohol psychoses) and affordability of vodka between 1990 and 2010 were compared. The time series analysis revealed that 1% increase in vodka affordability is associated with an increase in liver cirrhosis mortality of 0,77%, an increase in pancreatitis mortality of 0.53%, an increase in mortality from alcoholism and alcohol psychoses of 0,70%. The major conclusion emerging from this study is that affordability of alcohol is one of the most important predictor of alcohol-related problems in a population. These findings provide additional evidence that decreasing in affordability of alcohol is an effective strategy for reducing alcohol consumption and alcohol-related harm.

  2. Alcohol Alert: Alcohol's Damaging Effects on the Brain (United States)

    ... Alcohol abuse and alcoholism. In: Nixon, S.J., ed. Neuropsychology for Clinical Practice. Washington, DC: American Psychological Press, ... alcoholic men: Relationships to changes in brain structure. Neuropsychology 14:178–188, 2000. (38) Rosenbloom, M. ; Sullivan, ...

  3. Lewis acid catalyzed cyclization of glycals/2-deoxy-D-ribose with arylamines: additional findings on product structure and reaction diastereoselectivity. (United States)

    Du, Chengtang; Li, Fulong; Zhang, Xuefeng; Hu, Wenxiang; Yao, Qizheng; Zhang, Ao


    The cyclization reactions of arylamines with 2-deoxy-D-ribose or glycals were reinvestigated in the current report. In the montmorillonite KSF- or InCl(3)-initiated reactions of 2-deoxy-D-ribose with arylamines, a pair of diastereomeric tetrahydro-2H-pyran-fused tetrahydroquinolines was obtained in a nearly 1:1 ratio where the structure of one diastereomer was incorrectly assigned in the literature. Meanwhile, the diastereoselectivity in InBr(3)-catalyzed cyclization of glycals with arylamines was also incorrectly reported previously. It was found that high diastereomeric selectivity was achieved only when a C5-substituted glycal was used; otherwise, a pair of diastereomers was obtained in moderate yield with 1:1 diastereomeric ratio. Furthermore, tetrahydrofuran-fused tetrahydroquinolines 5b and 5b' were also prepared successfully by using TBDPS-protected ribose as the glycal precursor and montmorillonite KSF as the activator.

  4. FastStats: Alcohol Use (United States)

    ... this? Submit What's this? Submit Button NCHS Home Alcohol Use Recommend on Facebook Tweet Share Compartir Data ... alcoholic liver disease deaths: 19,388 Number of alcohol-induced deaths, excluding accidents and homicides: 30,722 ...

  5. Multimetallic complexes and functionalized nanoparticles based on unsymmetrical dithiocarbamate ligands with allyl and propargyl functionality. (United States)

    Hurtubise, Venesia L; McArdle, James M; Naeem, Saira; Toscani, Anita; White, Andrew J P; Long, Nicholas J; Wilton-Ely, James D E T


    The new, unsymmetrical dithiocarbamate ligands, KS2CN(CH2CH═CH2)Me and KS2CN(CH2C≡CH)Me, are formed from the respective amines on reaction with KOH and carbon disulfide. The homoleptic complexes [Ni{S2CN(CH2CH═CH2)Me}2] and [M{S2CN(CH2C≡CH)Me}2] (M = Ni, Pd, Pt) are formed on reaction with suitable metal precursors. Conversion between the two pendant functionalities was confirmed by hydrogenation of [Ni{S2CN(CH2C≡CH)Me}2] to yield [Ni{S2CN(CH2CH═CH2)Me}2]. The monodithiocarbamate compounds of group 8, 10, and 11 metals, [Ru{S2CN(CH2CH═CH2)Me}(dppm)2](+), [Ru(CH═CHC6H4Me-4){S2CN(CH2CH═CH2)Me}(CO)(PPh3)2], [Ni{S2CN(CH2CH═CH2)Me}(dppp)](+), and [Au{S2CN(CH2CH═CH2)Me}(PPh3)] were formed successfully. Using KS2CN(CH2C≡CH)Me, the complex [Ru{S2CN(CH2C≡CH)Me}(dppm)2](+) was obtained from cis-[RuCl2(dppm)2]. One palladium example, [Pd{S2CN(CH2C≡CH)Me}(PPh3)2](+), was also isolated in low yield. However, under the typical conditions employed, a rearrangement reaction prevented isolation of further group 10 propargyl-dithiocarbamate products. Over the extended reaction time required, Me(HC≡CCH2)NCS2(-) was found to undergo a remarkable, atom-efficient cyclization to form the thiazolidine-2-thione, H2C═CCH2N(Me)C(═S)S, in high yield, with MeC═CHN(Me)C(═S)S as the minor product. The reactivity of the pendant triple bonds in [Ni{S2CN(CH2C≡CH)Me}2] was probed in the reaction with [RuH(CO)(S2P(OEt)2)(PPh3)2] to form the trimetallic example [Ni{S2CN(Me)CH2CH═CHRu(CO)(S2P(OEt)2)(PPh3)2}2], while the copper(I) catalyzed reaction with benzylazide yielded the triazole product, [Ni{S2CN(Me)CH2(C2HN3)Bz}2]. KS2CN(CH2C≡CH)Me was also used to prepare the gold nanoparticles, Au@S2CN(CH2C≡CH)Me. Structural studies are reported for [Ru(CH═CHC6H4Me-4){S2CN(CH2CH═CH2)Me}(CO)(PPh3)2] and [Ru{S2CN(CH2C≡CH)Me}(dppm)2]PF6.

  6. Mechanistic Insights into the Palladium(II)-catalyzed Intramolecular Cyclization of o-Alkynylphenylphosphonamide and N-(o-Alkynylphenyl)acetamide by Electrospray Ionization Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jing; TANG Wei; GUO Yinlong; DING Yixiang


    The intramolecular cyclization of o-alkynylphenylphosphonamide and N-(o-alkynylphenyl)acetamide was monitored by electrospray ionization mass spectrometry(ESI-MS)and its tandem version(ESI-MS/MS).The proposed intermediates were successfully intercepted and characterized.In addition,the intermediates composed of the substrate coordinated to the palladium(Ⅱ)center in the reaction of o-alkynylphenylphosphonamide were unexpected before,and this interesting phenomenon of the substrate coordination seems associated with the unique structure of substrates.

  7. Synthesis of 1,2,4-Triazolo[4,3-a]pyridines and Related Heterocycles by Sequential Condensation and Iodine-Mediated Oxidative Cyclization. (United States)

    Li, Ertong; Hu, Zhiyuan; Song, Lina; Yu, Wenquan; Chang, Junbiao


    A facile and efficient approach to access 1,2,4-triazolo[4,3-a]pyridines and related heterocycles has been accomplished through condensation of readily available aryl hydrazines with corresponding aldehydes followed by iodine-mediated oxidative cyclization. This transition-metal-free synthetic process is broadly applicable to a variety of aromatic, aliphatic, and α,β-unsaturated aldehydes, and can be conveniently conducted on the gram scale.

  8. Deconstructing selectivity in the gold-promoted cyclization of alkynyl benzothioamides to six-membered mesoionic carbene or acyclic carbene complexes

    KAUST Repository

    Vummaleti, Sai V. C.


    We demonstrate that the experimentally observed switch in selectivity from 5-exo-dig to 6-endo-dig cyclization of an alkynyl substrate, promoted by Au I and AuIII complexes, is connected to a switch from thermodynamic to kinetic reaction control. The AuIII center pushes alkyne coordination toward a single Au-C(alkyne) σ-bond, conferring carbocationic character (and reactivity) to the distal alkyne C atom. © 2014 American Chemical Society.


    Institute of Scientific and Technical Information of China (English)

    HUANG Junlian; SUN Meng


    The degradation mechanism of photocrosslinking products formed by cyclized polyisoprene-diazide system under the influence of the different alkyl benzene sulfonic acids was studied. The effects ofalkyl chain length and the concentration of alkyl benzene sulfonic acids on the rate of degradation reaction were discussed. It was found that in the initial stage of degradation, the cyclicity ratio and the average fused ring number did not change considerably, but the percentage of uncyclized parts content varied significantly. The suitable mechanism was supposed.

  10. The intramolecular cyclization of bis-2,5-dimethylene-2,5-dihydrofurans and bis-2,5-dimethylene-2,5-dihydrothiophenes: An approach to macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Klumpp, D.A.


    The first two papers of this dissertation present our work with the intramolecular cyclizations of a pair of p-quinodimethanes. The p-quinodimethanes were generated by flash vacuum pyrolysis (FVP) and were linked by a bridging chain. The third paper of this dissertation presents our work in the synthetic manipulation of the products formed from the intramolecular reactions of the p-quinodimethanes.

  11. Hydride-induced anionic cyclization: an efficient method for the synthesis of 6-H-phenanthridines via a transition-metal-free process. (United States)

    Chen, Wei-Lin; Chen, Chun-Yuan; Chen, Yan-Fu; Hsieh, Jen-Chieh


    A novel procedure for hydride-induced anionic cyclization has been developed. It includes the reduction of a biaryl bromo-nitrile with a nucleophilic aromatic substitution (S(N)Ar). A range of polysubstituted 6-H-phenanthridines were so obtained in moderate to good yield with good substrate tolerance. This method involves a concise transition-metal-free process and was applied to synthesize natural alkaloids.

  12. Molecular basis of alcoholism. (United States)

    Most, Dana; Ferguson, Laura; Harris, R Adron


    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.

  13. Alcoholism and diabetes mellitus. (United States)

    Kim, Soo-Jeong; Kim, Dai-Jin


    Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  14. Alcoholism and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Soo-Jeong Kim


    Full Text Available Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM, which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  15. Children of Alcoholics (United States)

    ... 11) • Abuse of drugs or alcohol; or • Aggression towards other children • Risk taking behaviors • Depression or suicidal thoughts or behavior Some children of alcoholics may cope by taking the role of responsible "parents" within the family and among friends. They may ...

  16. Fetal Alcohol Spectrum Disorder (United States)

    Caley, Linda M.; Kramer, Charlotte; Robinson, Luther K.


    Fetal alcohol spectrum disorder (FASD) is a serious and widespread problem in this country. Positioned within the community with links to children, families, and healthcare systems, school nurses are a critical element in the prevention and treatment of those affected by fetal alcohol spectrum disorder. Although most school nurses are familiar…

  17. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)



    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  18. Alcohol and atherosclerosis

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Grønbaek, Morten


    Light to moderate alcohol intake is known to have cardioprotective properties; however, the magnitude of protection depends on other factors and may be confined to some subsets of the population. This review focuses on factors that modify the relationship between alcohol and coronary heart diseas...

  19. Leisure and Alcohol Expectancies. (United States)

    Carruthers, Cynthia P.


    Presents the results of a study that investigated the ways individuals expected drinking to affect their leisure experiences, and the relationship of those expectancies to alcohol consumption patterns. Data from a sample of 144 adults indicated they expected alcohol to positively affect their leisure experiences. (SM)

  20. Isolation and recovery of cellulose from waste nylon/cotton blended fabrics by 1-allyl-3-methylimidazolium chloride. (United States)

    Lv, Fangbing; Wang, Chaoxia; Zhu, Ping; Zhang, Chuanjie


    Development of a simple process for separating cellulose and nylon 6 from their blended fabrics is indispensable for recycling of waste mixed fabrics. An efficient procedure of dissolution of the fabrics in an ionic liquid 1-allyl-3-methylimidazolium chloride ([AMIM]Cl) and subsequent filtration separation has been demonstrated. Effects of treatment temperature, time and waste fabrics ratio on the recovery rates were investigated. SEM images showed that the cotton cellulose dissolved in [AMIM]Cl while the nylon 6 fibers remained. The FTIR spectrum of regenerated cellulose (RC) was similar with that of virgin cotton fibers, which verified that no other chemical reaction occurred besides breakage of hydrogen bonds during the processes of dissolution and separation. TGA curves indicated that the regenerated cellulose possessed a reduced thermal stability and was effectively removed from waste nylon/cotton blended fabrics (WNCFs). WNCFs were sufficiently reclaimed with high recovery rate of both regenerated cellulose films and nylon 6 fibers.

  1. Synthesis, spectroscopic characterization and solution behavior of new tin tetrachloride adducts with γ-keto allyl phosphonates (United States)

    Elleuch, Haitham; Sanhoury, M. A. K.; Rezgui, F.


    Four new octahedral complexes of the type [SnCl4L2] (L = γ-keto allyl phosphonate) (1-4) were prepared and characterized by multinuclear (1H, 13C, 31P and 119Sn) NMR, IR spectroscopy and elemental analysis. The NMR data show, as expected, that these complexes exist in solution as mixtures of cis and trans isomers. More importantly, the solution structure was confirmed by 119Sn NMR spectra which show two triplets corresponding to the two isomers. In addition, the solution behavior of these complexes in the presence of excess ligand was studied by variable temperature NMR using the coalescence temperature method. The metal-ligand exchange activation energies were therefore determined and found to be in the range 57-60 kJ/mol. The effect of remote substituents on the metal-ligand interaction was studied and compared with closely related tin-phosphoryl complexes.

  2. Crystal structure of (E-4-(acetoxyimino-N-allyl-3-isopropyl-2,6-diphenylpiperidine-1-carbothioamide

    Directory of Open Access Journals (Sweden)

    T. Mohandas


    Full Text Available The title compound, C26H31N3O2S, crystallizes with two molecules (A and B in the asymmetric unit. In each case, the piperidine ring exists in a twist-boat conformation. The dihedral angle between the phenyl rings is 46.16 (12° in molecule A and 44.95 (12° in molecule B. In both molecules, the allyl side chain is disordered over two orientations in a 0.649 (9:0.351 (9 ratio for molecule A and 0.826 (10:0.174 (10 ratio for molecule B. In the crystal, neither molecule forms a hydrogen bond from its N—H group, presumably due to steric hindrance. A+A and B+B inversion dimers are formed, linked by pairs of weak C—H...O hydrogen bonds enclosing R22(22 ring motifs.

  3. Crystal structure of N-(1-allyl-3-chloro-4-ethoxy-1H-indazol-5-yl-4-methoxybenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Hakima Chicha


    Full Text Available In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å by 65.07 (8°. The allyl and ethoxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N—N—C—C = 111.6 (2 and C—C—O—C = −88.1 (2°]. In the crystal, molecules are connected by N—H...N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C—H...O hydrogen bonds, forming a three-dimensional network.

  4. Crystal structure of (Z-3-allyl-5-(4-chlorobenzylidene-2-sulfanylidene-1,3-thiazolidin-4-one

    Directory of Open Access Journals (Sweden)

    Rahhal El Ajlaoui


    Full Text Available In the title compound, C13H10ClNOS2, the dihedral angle between the rhodanine (r.m.s. deviation = 0.008 Å and 4-chlorobenzylidene rings is 1.79 (11°. The allyl group attached to the N atom, which lies almost perpendicular to the rhodanine ring, is disordered over two orientations in a 0.519 (13:0.481 (13 ratio. A short intramolecular C—H...S interaction closes an S(6 ring. In the crystal, molecules are linked by π–π stacking interactions [centroid–centroid separation = 3.600 (15 Å], generating inversion dimers.

  5. Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence. (United States)

    Harris, Golda G; Lombardi, Patrick M; Pemberton, Travis A; Matsui, Tsutomu; Weiss, Thomas M; Cole, Kathryn E; Köksal, Mustafa; Murphy, Frank V; Vedula, L Sangeetha; Chou, Wayne K W; Cane, David E; Christianson, David W


    Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg(2+) for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with three Mg(2+) ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis. Although neither full-length ScGS nor constructs of the C-terminal domain could be crystallized, homology models of the C-terminal domain were constructed on the basis of ∼36% sequence identity with the N-terminal domain. Small-angle X-ray scattering experiments yield low-resolution molecular envelopes into which the N-terminal domain crystal structure and the C-terminal domain homology model were fit, suggesting possible αα domain architectures as frameworks for bifunctional catalysis.

  6. Gas Phase Decarbonylation and Cyclization Reactions of Protonated N-Methyl- N-Phenylmethacrylamide and Its Derivatives Via an Amide Claisen Rearrangement (United States)

    Wang, Hao-Yang; Xu, Chu; Zhu, Wei; Liu, Guo-Sheng; Guo, Yin-Long


    Gas phase decarbonylation and cyclization reactions of protonated N-methyl- N-phenylmethacrylamide and its derivatives ( M·H+) were studied by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). MS/MS experiments of M·H+ showed product ions were formed by loss of CO, which could only occur with an amide Claisen rearrangement. Mechanisms for the gas phase decarbonylation and cyclization reactions were proposed based on the accurate m/z measurements and MS/MS experiments with deuterated compounds. Theoretical computations showed the gas phase Claisen rearrangement was a major driving force for initiating gas phase decarbonylation and cyclization reactions of M·H+. Finally, the influence of different phenyl substituents on the gas phase Claisen rearrangement was evaluated. Electron-donating groups at the para-position of the phenyl moiety promoted the gas phase Claisen rearrangement to give a high abundance of fragment ions [ M - CO + H]+. By contrast, electron-withdrawing groups on the phenyl moiety retarded the Claisen rearrangement, but gave a fragment ion at m/z 175 by loss of neutral radicals of substituents on the phenyl, and a fragment ion at m/z 160 by further loss of a methyl radical.

  7. Studies of cyclization reactions of linear cumulenes and heterocumulenes using the neutralization-reionization procedure and/or ab initio calculations. (United States)

    Wang, Tianfang; Bowie, John H


    A number of linear cumulenes and heterocumulenes have been made by charge stripping of anions of known bond connectivity in the source of a mass spectrometer. Some of these reactive molecules have been identified in interstellar molecular clouds. The structures of these neutrals may be investigated by reionization to a decomposing positive ion [the neutralization-reionization technique ((-)NR(+))], and/or by ab initio calculations. Energized linear cumulenes and heterocumulenes may undergo cyclization to form stable cyclic isomers. To cite a selection of the examples described in this review: (i) four-atom systems CCCC and some heterocumulenes CCCX (X=B, N, Al, Si, P) involve the formation of stable four-membered ring rhombic (also called kite and fan) structures. One of the cyclic molecules, cyclo-C(3) Si, has been detected in interstellar molecular clouds, (ii) five-atom cumulene and heterocumulene systems are more complex. Linear CCCCC rearranges the carbon skeleton by forming a C substituted rhomboid system, CCCCO forms a three-membered cyclic isomer, while nitrogen containing five-atom cumulenes effect nitrile to isonitrile interconversion via three-centered cyclized intermediates, and (iii) CCCCCC and CCCCBO cyclize to give unique six-membered ring systems.

  8. Pentoxifylline for alcoholic hepatitis

    DEFF Research Database (Denmark)

    Whitfield, Kate; Rambaldi, Andrea; Wetterslev, Jørn


    BACKGROUND: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects....... OBJECTIVES: To assess the benefits and harms of pentoxifylline in alcoholic hepatitis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS......,, and full text searches were conducted until August 2009. Manufacturers and authors were contacted. SELECTION CRITERIA: All randomised clinical trials of pentoxifylline in participants with alcoholic hepatitis compared to control were selected for inclusion. DATA COLLECTION AND ANALYSIS: Two...

  9. Alcohol consumption in adolescents

    Directory of Open Access Journals (Sweden)

    Ilona Plevová


    Full Text Available Aim: To determine the level of alcohol consumption in a selected group of adolescents. Design: A descriptive cross-sectional study. Methods: The data were obtained using a part of the standardized ESPAD questionnaire for assessing consumption of alcoholic beverages. The sample comprised 422 students from seven secondary schools of different types in the city of Ostrava. For statistical analysis, the chi-squared test and Fisher's exact test (for n ≤ 5 were used. The data were processed using Stata v. 10. Results: More than half of respondents first tried alcohol before the age of 15. The most frequent alcohol-related problems were unprotected sex, decreased school performance and problems with parents or friends. Incomplete families were found to be an important factor in adolescents preferring and more frequently drinking beer. Conclusion: The study confirmed results reported by the Europe-wide survey ESPAD, namely that adolescents start to drink alcohol as early as before they turn fifteen.

  10. Homocysteine and alcoholism. (United States)

    Bleich, S; Degner, D; Javaheripour, K; Kurth, C; Kornhuber, J


    Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

  11. Alcohol and sex. (United States)

    Vijayasenan, M E


    Diminished sexual functioning among individuals dependent upon alcohol has been assessed. Ninety-seven male patients entered the study, all inpatients as the unit for treatment of alcoholism and drug addiction (Villa 6) in Porirua Hospital, Porirua. The sexual ability of these patients before the development of alcoholism was also rated for the same items and this rating was used as a control. Of the 97 patients, 69 (71 percent) suffered from sexual dysfunction for a period more than 12 months prior to admission to hospital. The disturbances noted were diminished sexual desire (58 percent of patients), erectile impotence (16 percent), premature ejaculation (4 percent), ejaculatory in competence (22 percent). A high proportion of the alcoholics showed signs of sexual deviation-19 percent having performed sexual crimes and a further 28 percent having repeated thought of sexual crimes. The possible causes of alcohol induced sexual dysfunction are discussed.

  12. 78 FR 42530 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  13. 76 FR 78014 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review...., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism, National Institutes...

  14. 75 FR 10808 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, 5635...

  15. 78 FR 42529 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review....D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism,...

  16. 75 FR 57473 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse and Alcoholism, Office of Extramural Activities,...

  17. 75 FR 24961 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Extramural Activities, National Institutes of Health, National Institute on Alcohol Abuse & Alcoholism,...

  18. 76 FR 26308 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Scientific Review Administrator, National Institutes On Alcohol Abuse & Alcoholism National, Institutes...

  19. 75 FR 63494 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., Extramural Project Review Branch, EPRB, National Institute on Alcohol Abuse and Alcoholism,...

  20. 77 FR 22794 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting (United States)


    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism...