Sample records for aziridines

  1. Asymmetric Synthesis via Chiral Aziridines

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Harden, Adrian; Wyatt, Paul


    A series of chiral bis(aziridines) has been synthesised and evaluated as chelating ligands for a variety of asymmetric transformations mediated by metals [Os (dihydroxylation), Pd (allylic alkylation) Cu (cyclopropanation and aziridination, Li (1,2-addition of organolithiums to imines)]. In the b......A series of chiral bis(aziridines) has been synthesised and evaluated as chelating ligands for a variety of asymmetric transformations mediated by metals [Os (dihydroxylation), Pd (allylic alkylation) Cu (cyclopropanation and aziridination, Li (1,2-addition of organolithiums to imines...

  2. Synthesis of Cyclophellitol, Cyclophellitol Aziridine, and Their Tagged Derivatives

    NARCIS (Netherlands)

    Li, Kah-Yee; Jiang, Jianbing; Witte, Martin D.; Kallemeijn, Wouter W.; van den Elst, Hans; Wong, Chung-Sing; Chander, Sharina D.; Hoogendoorn, Sascha; Beenakker, Thomas J. M.; Codee, Jeroen D. C.; Aerts, Johannes M. F. G.; van der Marel, Gijs A.; Overkleeft, Herman S.


    Cyclitol epoxides and aziridines are potent and selective irreversible inhibitors of retaining glycosidases. We have previously reported on our studies on the use of activity-based probes derived from cyclophellitol and from its aziridine analogue for activity-based profiling of retaining -glucosida

  3. Facile Synthesis of N-Methylated Amino Acids from Chiral Aziridine-2-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jihye; Ha, Hyun-Joon [Hankuk University of Foreign Studies, Yongin (Korea, Republic of)


    Our recent success with the so-called N-methylative aziridine ring-opening reaction of nonactivated aziridines led us to the preparation of N-methylated amino acids. The nucleophilic ring-opening reaction of nonactivated aziridines requires the prerequisite of activation of aziridine as aziridinium ion, as shown in Scheme 1. We activate this nonactivated aziridine by methylation with methyltriflate to methylated aziridinium ion whose counterpart triflate anion is not nucleophilic enough to open the aziridine ring. The following external nucleophiles are applicable to the ringopening reaction, yielding N-methylated aziridine. In conclusion, we described an efficient preparation of Nmethylated α- and β-amino acids by N-methylative aziridine ring-opening reaction of aziridine-2-carboxylate and carboxamide with various nucleophiles.

  4. Asymmetric Synthesis of Fluoroamines from Chiral Aziridines

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyeonjeong; Yoon, Dooha; Ha, Hyunjoon [Hankuk Univ. of Foreign Studies, Yongin (Korea, Republic of); Son, Se In; Lee, Won Koo [Sogang Univ., Seoul (Korea, Republic of)


    We described an efficient preparation of fluoroamines by the ring-opening reactions of chiral aziridines with Et{sub 3}N·3HF. At most cases both regioisomers were obtained from the ring openings at C2 and C3 positions depending on the substituents at C2 of the starting substrates.The fluorinated organic molecules have attracted great attentions from synthetic and medicinal chemists with wide use of various agrochemicals and pharmaceuticals. Their uniqueness is originated from its electronic characteristics and the small size without altering the molecular conformations of non-fluorinated compounds. The fluorine is the second most widely used atom in the commercial drugs following the amine. Thereby, the elaboration of fluoro-amines bearing two most widely used atoms in drugs is one of the most challenging problems in drug synthesis and its development.

  5. Efficient, regioselective ring-opening of activated aziridine-2-carboxylates with [18F]fluoride

    DEFF Research Database (Denmark)

    Schjøth-Eskesen, Christina; Hansen, Paul Robert; Kjær, Andreas;


    Aziridines can undergo a range of ring-opening reactions with nucleophiles. The regio- and stereochemistry of the products depend on the substituents on the aziridine. Aziridine ring-opening reactions have rarely been used in radiosynthesis. Herein we report the ring opening of activated aziridin...

  6. Synthetic Aziridines in Medicinal Chemistry: A Mini-Review. (United States)

    Singh, Girija S


    Azaheterocyclic compounds are well-known to have diverse types of biological activity. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ring-strain, building blocks in organic synthesis, and its biological properties. Several novel compounds containing aziridine ring have been designed and synthesized recently by medicinal chemists for evaluating their biological profile. A number of compounds are reported as cysteine protease inhibitors, antibacterial, antifungal, anticancer, antileishmanial, and antimalarial agents. This review article summarizes the biological activity of such compounds. The preparation of such compounds is also described.

  7. Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

    KAUST Repository

    Zhang, Yan


    An amino-indanol derived chiral guanidine was developed as an efficient Brønsted base catalyst for the desymmetrization of meso-aziridines with both thiols and carbamodithioic acids as nucleophiles, which provided 1,2-difunctionalized ring-opened products in high yields and enantioselectivities. © The Royal Society of Chemistry.

  8. Spin-Selective Generation of Triplet Nitrenes: Olefin Aziridination through Visible-Light Photosensitization of Azidoformates. (United States)

    Scholz, Spencer O; Farney, Elliot P; Kim, Sangyun; Bates, Desiree M; Yoon, Tehshik P


    Azidoformates are interesting potential nitrene precursors, but their direct photochemical activation can result in competitive formation of aziridination and allylic amination products. Herein, we show that visible-light-activated transition-metal complexes can be triplet sensitizers that selectively produce aziridines through the spin-selective photogeneration of triplet nitrenes from azidoformates. This approach enables the aziridination of a wide range of alkenes and the formal oxyamination of enol ethers using the alkene as the limiting reagent. Preparative-scale aziridinations can be easily achieved under continuous-flow conditions.

  9. Amino Trans-position through the Chiral Aziridine

    Institute of Scientific and Technical Information of China (English)

    FENG Xi-Chun; LIANG Shu-Cai; SU Jiang-Tao; QIU Quo-Fu; HU Xian-Ming


    @@ Aziridines are valuable synthetic reagents and intermediates.[1~3] The highly strained three membered ring readily opens with excellent stereo- and regio-control to afford a wide variety of more stable ring opened chiral amines. (1 S, 2S)-1-Phenyl-2-amino-1,3-propanediol (1) is sulphonated at amino group and the hydroxyl group. Obtainning two kinds of sulphonated 1. Then it reacts in the conditions of Mitsunobu reagents (DEAD/PPh3) and alkaline, get α-phenyl-1-p-toluensulfonyl-aziridinemethanol (4). The chiral aziridine intermediate can aza-payne rearrange and ring opened with the reagent of LiAlH4 to get the N-tosyl-norephedrine (5) and 3-sulphurylamino-1aryl-propanol (7). The structure of these products was detected by IR, 1H NMR and MS spectra.

  10. Ring-opening of N-Tosyl Aziridines with Hydroxyl Compounds Catalyzed by Acidic Ionic Liquid

    Institute of Scientific and Technical Information of China (English)

    LI Yuling; GU Dagong; XU Xiaoping; JI Shunjun


    Ring-opening of two types of N-tosyl aziridines with hydroxyl compounds has been studied.The aziridines could react smoothly with alcohols in the presence of functional ionic liquid [hmim]HSO4 to afford the corresponding β-amino ethers in moderate to good yields with high regioselectivity.The recyclable property of [hmim]HSO4 was demonstrated in the process.

  11. PLA branching with anhydrides and tri-functional aziridine (United States)

    Gu, Liangliang; Xu, Yuewen; Naredla, Rajasekhar; Hoye, Thomas; Macosko, Christopher

    Branched PLA was prepared by melt blending with tri-functional aziridine (T-Az) and pyromellitic dianhydride (PMDA). 1HNMR, gel permeation chromatography (GPC) and rheology were used to characterize the topological structures of branched PLA. Fast reaction between PLA carboxyl end group and T-Az resulted in 3-arm stars and increased the molecular weight. However, the 3-arm stars did not show strain hardening behavior under extensional flow. After modifying PLA hydroxyl end group with PMDA, PLA can react with T-Az on both chain ends and form long chain branched structure, which showed strain hardening in extension. It was found that that only 10% of the PLA hydroxyl end groups reacted with PMDA. This work is supported by Center for Sustainable Polymers.

  12. Synthesis of chiral N-phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via Co(II-based metalloradical catalysis

    Directory of Open Access Journals (Sweden)

    Jingran Tao


    Full Text Available The Co(II complex of a new D2-symmetric chiral porphyrin 3,5-DiMes-QingPhyrin, [Co(P6], can catalyze asymmetric aziridination of alkenes with bis(2,2,2-trichloroethylphosphoryl azide (TcepN3 as a nitrene source. This new Co(II-based metalloradical aziridination is suitable for different aromatic olefins, producing the corresponding N-phosphorylaziridines in good to excellent yields (up to 99% with moderate to high enantioselectivities (up to 85% ee. In addition to mild reaction conditions and generation of N2 as the only byproduct, this new metalloradical catalytic system is highlighted with a practical protocol that operates under neutral and non-oxidative conditions.

  13. Enantioselective synthesis of diaryl aziridines using tetrahydrothiophene-based chiral sulfides as organocatalysts. (United States)

    Huang, Meng-Ting; Wu, Hsin-Yi; Chein, Rong-Jie


    This work describes catalytic and asymmetric aziridinations (15 examples, 95-98% ee) of benzyl bromide and imines via the imino Corey-Chaykovsky reaction using (thiolan-2-yl)diarylmethanol benzyl ether as an organocatalyst. The catalyst and analogues thereof were prepared through an expeditious and efficient synthetic route featuring a double nucleophilic substitution and Shi epoxidation as key steps.

  14. Novel Synthesis of 8-Deaza-5,6,7,8-tetrahydroaminopterin Analogues via an Aziridine Intermediate

    Directory of Open Access Journals (Sweden)

    Zhili Zhang


    Full Text Available An efficient method for the construction of the tetrahydrofolate skeleton is described. Starting from pterin analogues and aromatic amines, 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives and the heterocyclic benzoyl isosteres were synthesized via a novel aziridine intermediate. Following this method, the byproducts of carbon-nitrogen bond hydrogenolysis in traditional synthetic strategy can be completely avoided.

  15. Ring opening of a resin-bound chiral aziridine with phenol nucleophiles

    DEFF Research Database (Denmark)

    Ottesen, Lars Korsgaard; Jaroszewski, Jerzy W; Franzyk, Henrik


    An efficient and versatile solid-phase route for the preparation of aryl-alkyl ethers is described. Regioselective ring opening of a resin-bound chiral aziridine with phenolic nucleophiles constitutes the key feature of the present protocol that allows incorporation of fluorescent moieties...

  16. Enantio- and diastereoselectivities in chiral sulfur ylide promoted asymmetric aziridination reactions. (United States)

    Janardanan, Deepa; Sunoj, Raghavan B


    Density functional theory investigation on the factors controlling enantio- and diastereoselection in asymmetric aziridination reaction by the addition of chiral bicyclic sulfur ylides to substituted aldimines is presented. High levels of enantioselection are predicted toward the formation of (2S,3S)-cis and (2R,3S)-trans aziridines by the addition of stabilized ylide (R = COMe) respectively to SO2Me and CO2Me protected aldimines. Similarly, high %ee is predicted for the formation of (2S,3R)-cis aziridines from semistabilized (R = Ph) ylide. Moderate to high levels of diastereoselectivity is noticed as well. The present study highlights that a correct prediction on extent of enantioselection requires the knowledge of the activation barriers for elementary steps beyond the initial addition step. In the case of stabilized ylides the ring-closure (or elimination of sulfur compound) is found to be crucial in controlling enantio- and diastereoselection. A cumulative effect of electronic as well as other weak interactions is identified as factors contributing to the relative energies of transition states leading to enantio- and diastereomeric products for the stabilized ylide addition to aldimines. On the contrary, steric control appears quite dominant with semistabilized ylide addition. With the smallest substituent on ylide (R = Me), high enantioselectivity is predicted for the formation of (2R,3R)-trans aziridines although the %de in this case is found to be very low.

  17. Enantioselective Addition of Organolithium Reagents to Imines Mediated by C2-Symmetric Bis(aziridine) Ligands

    DEFF Research Database (Denmark)

    Johansson, F.; Tanner, David Ackland


    The C-2-symmetric bis(aziridine) ligands 1 - 5 have been screened in the enantioselective addition of organolithium reagents to imines. Ligand 1 (used in stoichiometric amounts) was found to be superior in terms of chemical yield and enantioselectivity, the best result being 90% yield and 89% e.e...

  18. Bifunctional Asymmetric Catalysis with Hydrogen Chloride: Enantioselective Ring-Opening of Aziridines Catalyzed by a Phosphinothiourea. (United States)

    Mita, Tsuyoshi; Jacobsen, Eric N


    Ring-opening of aziridines with hydrogen chloride to form β-chloroamine derivatives is catalyzed by a chiral phosphinothiourea derivative in high yields and with high enantioselectivities. On the basis of (31)P NMR studies, activation of HCl appears to proceed via quantitative protonation of the catalyst to afford a phosphonium chloride complex.


    Institute of Scientific and Technical Information of China (English)

    Fei Xie; Zong-hui Liu; De-qing Wei


    A kind of aziridine crosslinkers was synthesized and used to crosslink acrylate copolymers. The crosslinking properties and curing kinetics of the resin were studied. It was found that with the increase of the content of crosslinker in the emulsion, the mechanical properties and solvent resistance of the resin will be apparently improved, but its glass transition temperature (Tg) is very low. The lowest amount of crosslinker used in the acrylic resin emulsion is 0.25%. Curing kinetics studied by DSC show that this curing reaction occurs readily because the apparent activation energy of the reaction is low(65.1 KJ/mol). These results demonstrate that the aziridine crosslinker is indeed a low temperature crosslinking agent and can be used at room temperature.

  20. Tri-n-butylphosphine Mediated Ring-Opening Reactions of Aziridines or Epoxides with Diphenyl Diselenide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wan-Xuan; YE Kang; RUAN Shan; CHEN Zu-Xing; XIA Qing-Hua


    Aziridines and epoxides were reacted with diphenyl diselenide in the presence of a stoichiometric amount of (n-Bu)3P, respectively, giving β-amino-or β-hydroxy selenides in moderate to excellent yields under mild conditions. In the reactions the (n-Bu)3P might act as a reductant though it was a nucleophilic catalyst in other similar ring-opening reactions.

  1. Tri-n-butylphosphane catalyzed ring opening of aziridines with secondary amines

    Institute of Scientific and Technical Information of China (English)

    Wan Xuan Zhang; Li Su; Wei Gang Hu; Jie Zhou


    Ring opening of aziridine with dialkyl amine took place readily in the presence of catalytic amounts of tri-n-butylphosphane (10 mol%) in the mixture of CH3CN/H2O (10:1),giving corresponding vicinal diamines in mediate to high yields (58-95%) with good regioselecfivifie,while aromatic secondary amine could not react under the same condifions.Tti-n-butylphosphane exhibited different catalytic selectivity to amines from Lewis acid catalysts.

  2. Mechanism and electronic effects in nitrogen ylide-promoted asymmetric aziridination reaction. (United States)

    Rajeev, Ramanan; Sunoj, Raghavan B


    The mechanism and stereoselectivity of the aziridination reaction between guanidinium ylide and a series of para-substituted benzaldehydes have been studied by using density functional theory methods. The mechanistic details and analyses of the key elementary steps involved in (a) the addition of nitrogen ylide to benzaldehydes and (b) subsequent fragmentation of the resulting oxaspirocyclic intermediate are presented. The relative energies of important transition states and intermediates are found to be useful toward rationalizing reported diastereoselective product formation. The relative energies of the key transition states could be rationalized on the basis of the differences in steric, electrostatic, and other stabilizing weak interactions. The deformation analysis of the transition state geometries exhibited good correlation with the predicted activation barriers. The changes in cis/trans diastereoselectivity preferences upon changes in the electron donating/withdrawing abilities of the para substituents on benzaldehyde are identified as arising due to vital differences in the preferred pathways. The large value of reaction constant (ρ > 4.8) estimated from the slope of good linear Hammett plots indicated high sensitivity to the electronic nature of substituents on benzaldehyde. The formation of trans-aziridine in the case of strong electron donating groups and cis-aziridines with weakly electron donating/withdrawing group has been explained by the likely changes in the mechanistic course of the reaction. In general, the predicted trends are found to be in good agreement with the earlier experimental reports.

  3. Computational investigations on the general reaction profile and diastereoselectivity in sulfur ylide promoted aziridination. (United States)

    Janardanan, Deepa; Sunoj, Raghavan B


    Mechanism and diastereoselectivity of sulfur ylide promoted aziridination reactions were studied by density functional theory with inclusion of solvent effects through the continuum solvation model. The general reaction pathway was modeled for the addition of substituted sulfur ylides (Me(2)S(+)CH(-)R) to an aldimine ((E)-methyl ethylidenecarbamate, MeHC=NCO(2)Me). The nature of the substituents on the ylidic carbon atom substantially affects the reaction profile. The stabilized (R=COMe) and semistabilized (R=Ph) ylides follow a cisoid addition mode leading to trans aziridines via anti betaine intermediates. The simplest model ylide (unstabilized, R=H) underwent cisoid addition in a similar fashion. In the case of stabilized ylides product diastereoselectivity is controlled by the barriers of the elimination step leading to the 2,3-trans aziridine, whereas it is decided in the addition step in the case of semistabilized ylides. The importance of steric and electronic factors in diastereoselective addition (2 and 5) and elimination (5) transition states was established. Comparison of results obtained with the gas-phase optimized geometries and with the fully optimized solvent-phase geometries reveals that the inclusion of solvent effects does not bring about any dramatic changes in the reaction profiles for all three kinds of ylides. In particular, diastereoselectivity for both kinds of ylides was found to be nearly the same in both these approaches.

  4. A comparative Study of C2-Symmetric Bis(aziridine) Ligands in Some Transition Metal-Mediated Asymmetric Transformations

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Johansson, Fredrik; Harden, Adrian;


    A comparative study has been made of the performance of differently substituted Ca-symmetric bis(aziridine) ligands in a variety of metal-mediated asymmetric reactions. The metals studied were osmium (dihydroxylation), palladium (allylic alkylation) and copper (cyclopropanation and aziridination......), the ligands being chosen so as to allow evaluation of both electronic and steric effects. The electronic effects were most pronounced for complexes of palladium, which seem to bind rather loosely to this type of ligand. For the other metals, steric effects play a more important role. (C) 1998 Elsevier Science...

  5. Synthesis of mono-fluorinated functionalized cyclopropanes and aziridines using the α-fluorovinyl diphenyl sulfonium salt. (United States)

    Hirotaki, Kensuke; Takehiro, Yui; Kamaishi, Ryo; Yamada, Yasunori; Hanamoto, Takeshi


    The α-fluorovinyl diphenyl sulfonium salt 1 is attractive due to its high potential for the synthesis of mono-fluorinated cyclopropanes and aziridines as useful three-membered rings. The synthetically useful salt 1 is readily prepared from α-fluorovinyl phenyl sulfide and diphenyl iodonium salt in one step.

  6. Uncatalyzed thermal gas phase aziridination of alkenes by organic azides. Part I: Mechanisms with discrete nitrene species

    Indian Academy of Sciences (India)



    Alkene aziridination by azides through uncatalyzed thermal gas phase routes has been studiedusing the DFT B3LYP/6-31G(d,p) method, where the possible role of discrete nitrene intermediates is emphasized.The thermal decomposition of azides is studied using the MP2/aug-cc-pVDZ strategy as well. The MP2(but not the B3LYP) results discount the existence of singlet alkylnitrenes where the alkyl group has an α-hydrogen. Addition of the lowest lying singlet and triplet nitrenes R-N (R = H, Me, Ac) to four different alkenesubstrates leading to aziridine formation was studied by the B3LYP method. Singlet nitrenes with alkenes canyield aziridines via a concerted mechanism, where H-N insertion takes place without a barrier, whereas Me-Nshows larger barriers than Ac-N. Methyl substitution in the alkene favors this reaction. Triplet nitrene additionto alkenes is studied as a two-step process, where the initially formed diradical intermediates cyclize to formaziridines by ISC (intersystem crossing) and collapse. Scope for C-C bond rotation in the diradical leads to lossof stereochemical integrity for triplet nitrene addition to cis- and trans-2-butenes. Geometries of the transitionstates in the various reaction steps studied here are described as “early” or “late” in good accordance with theHammond postulate.

  7. Aziridine- and Azetidine-Pd Catalytic Combinations. Synthesis and Evaluation of the Ligand Ring Size Impact on Suzuki-Miyaura Reaction Issues

    Directory of Open Access Journals (Sweden)

    Hamza Boufroura


    Full Text Available The synthesis of new vicinal diamines based on aziridine and azetidine cores as well as the comparison of their catalytic activities as ligand in the Suzuki-Miyaura coupling reaction are described in this communication. The synthesis of three- and four-membered ring heterocycles substituted by a methylamine pendant arm is detailed from the parent nitrile derivatives. Complexation to palladium under various conditions has been examined affording vicinal diamines or amine-imidate complexes. The efficiency of four new catalytic systems is compared in the preparation of variously substituted biaryls. Aziridine- and azetidine-based catalytic systems allowed Suzuki-Miyaura reactions from aryl halides including chlorides with catalytic loadings until 0.001% at temperatures ranging from 100 °C to r.t. The evolution of the Pd-metallacycle ring strain moving from azetidine to aziridine in combination with a methylamine or an imidate pendant arm impacted the Suzuki-Miyaura reaction issue.

  8. Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used as bonding agent for rocket solid propellants

    Directory of Open Access Journals (Sweden)

    Aparecida M. Kawamoto


    Full Text Available A rapid, expedient and enantioselective method for the synthesis of beta-hydroxy amines and monosubstituted aziridines in up to 99% e.e., via asymmetric transfer hydrogenation of a-amino ketones and cyclisation through treatment with tosyl chloride and base, is described. (1R,2R-N-(para-toluenesulfonyl-1,2-ethylenediamine with formic acid has been utilised as a ligand for the Ruthenium (II catalysed enantioselective transfer hydrogenation of the ketones.The chiral 2-methyl aziridine, which is a potentially more efficient bonding agent for Rocket Solid Propellant has been successfully achieved.

  9. Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides (United States)

    Huck, Lena; González, Juan F; de la Cuesta, Elena


    Summary A sequential three-component process is described, starting from 3-arylmethylene-2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step. PMID:27559422

  10. Unprecedented trinuclear Ag(I) complex with 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine as an efficient catalyst for the aziridination of olefins. (United States)

    Safin, Damir A; Pialat, Amélie; Korobkov, Ilia; Murugesu, Muralee


    An unprecedented trinuclear heteroleptic Ag(I) complex was isolated using a stable multidentate 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine (TPymT) ligand. The obtained compound is an efficient catalyst for the direct aziridination of terminal olefins.

  11. Investigation of the role of aziridine bonding agents on the aging of the composite solid rocket propellant(CSRP)

    Institute of Scientific and Technical Information of China (English)

    Amged A Ali; ZHANG Jian-wei; CAI Guo-biao


    The role of bonding agents on the aging characteristics is one of the important research topics.Aging program of the prepared propellant samples was conducting as follows:Five samples,two free of bonding agents,and three containing an aziridine based bonding agents (MAPO,HX-752,MAT4),four samples based on different bonding and curing agents all were aged at 70℃.The prepared bonding agent"MAT4"gave remarkable improvements and resulted in highly stable mechanical properties comparing with HX-752 or MAPO.The selected bonding agents family inhibited the rate of decomposition of the propellants during the aging periods and supported the propellant matrix against decomposition at the elevated temperatures.

  12. Exploration of aziridine- and β-lactam-based hybrids as both bioactive substances and synthetic intermediates in medicinal chemistry. (United States)

    Vandekerckhove, Stéphanie; D'hooghe, Matthias


    The concept of pharmacophore hybridization is attracting an increasing interest from medicinal chemists. Whereas the main motivation for the application of this methodology relates to the pharmacological advantages associated with hybrid molecules, molecular hybridization can also deliver a synthetic advantage through selective chemical modification of the more reactive entity within hybrid systems. Moreover, if both features are combined, new hybrid structures result displaying both a biological and a synthetic benefit, and elaboration of this methodology might culminate in structural diversity and chemical novelty. In this perspective, a new approach based on hybrid structures combining a biologically interesting yet rather chemically reactive nucleus with a privileged heterocyclic scaffold is discussed by means of β-lactam-purine chimeras useful in antiviral research and aziridine-(iso)quinoline hybrids for antimalarial purposes.

  13. Dramatic effects of halogen substitution and solvent on the rates and mechanisms of nucleophilic substitution reactions of aziridines. (United States)

    Banks, Harold D


    In a previous study we reported that fluorine substitution at the carbon positions of aziridine results in profound enhancements of the rate of reaction with ammonia, a typical nucleophile, in the gas phase. In this study the investigation is extended to include chloro- and bromoaziridines. Because syntheses are largely performed in the condensed phase, the present computational investigation [(MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level] was conducted with three typical solvents that cover a wide range of polarity: THF, CH3CN, and H2O. Nucleophiles can react with haloaziridines 1 by displacing a substituted amide ion by means of an SN2 mechanism (pathway a), producing 1,2-diaminohaloethanes (from the initially formed dipolar species 2). Alternatively, a rearrangement mechanism involving rate-determining departure of a halide ion (pathway b) to form an imidoyl halide, 3, is possible. Transition-state theory was used to compute relative reaction rates of these mechanistic possibilities and to assess the role of the halogen substituents and the reaction solvent. Gas-phase results provided the basis of mechanistic insights that were more apparent in the absence of intermolecular interactions. Fluoroaziridines were found to react at accelerated rates relative to aziridine exclusively by means of the a Menshutkin-type mechanism (SN2) in each solvent tested, while the reactions of the chloro- and bromoaziridines could be directed toward 2 in the highly nonpolar solvent, cyclohexane, or toward 3 in the more polar solvents. An assessment is made of the feasibility of using this chemistry of the haloazirdines in the synthetic laboratory.

  14. Chelating compounds as potential flash rust inhibitors and melamine & aziridine cure of acrylic colloidal unimolecular polymers (CUPs) (United States)

    Mistry, Jigar Kishorkumar

    Waterborne coatings on ferrous substrates usually show flash rusting which decreases the adhesion of the coating and the corrosion products can form a stain. Chelating compounds were investigated as potential flash rust inhibitors. Compounds being evaluated include amine alcohols, diamines and sulfur containing amines. A new corrosion inhibitor 2,5-bis(thioaceticacid)-1,3,4-thiadiazole (H2ADTZ) was synthesized and its performance characteristics were evaluated. It was noted that the observed structure of 1,3,4-thiadiazolidine-2,5-dithione (also known as 2,5-dimercapto-1,3,4-thiadiazole (DMTD or DMcT)) has been previously reported in three different tautomeric forms including -dithiol and -dithione. The relative stability of each form as well as the synthesis and characterization of the structures of mono- and dialkylated forms of 5-mercapto-1,3,4-thiadiazole-2(3H)-thione (MTT) were examined. The methods of X-ray crystallography, NMR spectroscopy and ab-initio electronic structure calculations were combined to understand the reactivity and structure of each compound. Polymers were synthesized with a 1:7 or 1:8 ratio of acrylic acid to acrylate monomers to produce an acid rich resin. The polymers were reduced and solvent stripped to produce Colloidal Unimolecular Polymers (CUPs). These particles are typically 3-9 nanometers in diameter depending upon the molecular weight. They were then formulated into a clear coating with either a melamine (bake) or an aziridine (ambient cure) and then cured. The melamine system was solvent free, a near zero VOC and the aziridine system was very low to near zero VOC. The coatings were evaluated for their MEK resistance, adhesion, hardness, gloss, flexibility, wet adhesion, abrasion and impact resistance properties.

  15. Reactions of Cu(I)Br with aziridine derivatives. Synthesis, characterization and crystal structures of monomeric, dimeric and hexameric aziridine (= az) complexes of the formal type [CuBr(az)2]n (n = 1, 2) and [CuBr(az)]6. (United States)

    Bobka, Roman; Roedel, J Nicolas; Wirth, Stefan; Lorenz, Ingo-Peter


    The first syntheses of monomeric and oligomeric aziridine complexes of copper(I) are described. Cu(I)Br (1) reacts with a series of different aziridine derivatives (C(2)H(3)PhNH (2), C(2)H(2)Me(2)NH (3), C(2)H(2)Me(2)NC(2)H(2)Me(2)NH(2) (4)) to give the neutral dimeric complex [CuBr(C(2)H(3)PhNH)(2)](2) (5) and the ionic hexameric complex [Cu(6)Br(5)(C(2)H(2)Me(2)NH)(6)]Br (6) with terminal bound aziridine ligands as well as the neutral monomeric complex [CuBr(C(2)H(2)Me(2)NC(2)H(2)Me(2)NH(2))] (7) where the dimerized aziridine acts as a N,N'-chelating ligand. After purification, all of the complexes were fully characterized and their IR, (1)H and (13)C NMR spectra are reported and discussed. The single crystal structure analysis revealed distorted tetrahedral geometry for the copper(I) centres in the complexes 5 and 6 and a trigonal planar structure for complex 7. In the oligomers the copper centres are bridged by two μ(2)- (5) or two μ(3)- and three μ(4)-bromido ligands (6), respectively.

  16. A Stereoselective Route to Tetrahydrobenzoxazepines and Tetrahydrobenzodiazepines via Ring-Opening and Aza-Michael Addition of Activated Aziridines with 2-Hydroxyphenyl and 2-Aminophenyl Acrylates. (United States)

    Shahi, Chandan Kumar; Bhattacharyya, Aditya; Nanaji, Yerramsetti; Ghorai, Manas K


    A simple and efficient synthetic route to 2,3,4,5-tetrahydrobenzoxazepines and -benzodiazepines bearing easily functionalizable appendages has been developed by ring-opening of activated aziridines with 2-hydroxyphenyl acrylates and 2-aminophenyl acrylate, respectively, and subsequent intramolecular C-N bond formation through palladium-catalyzed aza-Michael reaction. The straightforward synthetic approach delivers the desired molecular scaffolds in high yields (up to 82%) with excellent stereoselectivity (ee up to 94%).

  17. One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction. (United States)

    Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Han, Jianlin; Li, Guigen; Pan, Yi


    We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .

  18. Assessment of the repair and damage of DNA induced by parent and reduced RSU-1069, a 2-nitroimidazole-aziridine

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, P.; Cunniffe, S.M.


    The cellular repair and damage of DNA induced by parent and reduced RSU-1069, a 2-nitroimidazole-aziridine, was assessed at both the molecular and cellular level. At the molecular level, after in vitro incubation with parent or reduced RSU-1069, plasmid DNA was transfected into Escherichia coli (AB1157) with subsequent selection for gene expression. For equivalent levels of DNA strand breakage following such treatment it is evident from the relative transformation frequencies that interactions with reduced RSU-1069 lead to DNA damage consistent with bifunctional action of a metabolite(s). At the cellular level, the cytoxicity of RSU-1069 was determined for a series of repair deficient mutants of E. coli under both aerobic and hypoxic conditions. The differential aerobic:hypoxic cytotoxicity ratio is approximately 3. We conclude that the repair of cellular DNA damage induced by RSU-1069 involves activation of the gene products under the control of the recA gene and not those under the control of the ada gene. The ability of cellular systems to repair damage induced by RSU-1069 may play a significant role in determining its efficiency to act as a hypoxic cell radiosensitizer and a hypoxia selective cytotoxin.

  19. Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

    Directory of Open Access Journals (Sweden)

    U. K. Syam Kumar


    Full Text Available A novel synthetic methodology has been developed for the synthesis of diethyl 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates (also called 2-substituted pyrroline-4,5-dihydro-3,3-dicarboxylic acid diethyl esters by iodide ion induced ring expansion of 2-[(aziridin-1-yl-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters in very good to excellent yields under mild reaction conditions. The electronic and steric impact of the substituents on the kinetics of ring expansion of N-vinyl aziridines to pyrrolines has been studied. Various diversely substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines.

  20. Effects of mescaline and its derivative N-[3,4,5-trimethoxyphenylethyl]-aziridine on the spatial orientation of rats in a T-maze. (United States)

    Koupilová, M; Herink, J


    The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.

  1. Synthesis of cis-C-iodo-N-tosyl-aziridines using diiodomethyllithium: reaction optimization, product scope and stability, and a protocol for selection of stationary phase for chromatography. (United States)

    Boultwood, Tom; Affron, Dominic P; Trowbridge, Aaron D; Bull, James A


    The preparation of C-iodo-N-Ts-aziridines with excellent cis-diastereoselectivity has been achieved in high yields by the addition of diiodomethyllithium to N-tosylimines and N-tosylimine-HSO2Tol adducts. This addition-cyclization protocol successfully provided a wide range of cis-iodoaziridines, including the first examples of alkyl-substituted iodoaziridines, with the reaction tolerating both aryl imines and alkyl imines. An ortho-chlorophenyl imine afforded a β-amino gem-diiodide under the optimized reaction conditions due to a postulated coordinated intermediate preventing cyclization. An effective protocol to assess the stability of the sensitive iodoaziridine functional group to chromatography was also developed. As a result of the judicious choice of stationary phase, the iodoaziridines could be purified by column chromatography; the use of deactivated basic alumina (activity IV) afforded high yield and purity. Rearrangements of electron-rich aryl-iodoaziridines have been promoted, selectively affording either novel α-iodo-N-Ts-imines or α-iodo-aldehydes in high yield.

  2. Metodologia AGOA: a modelagem de clusters de hidratação no complexo aziridina···ácido fluorídrico AGOA methodology: modeling the hydration clusters for the aziridine···hydrofluoric complex

    Directory of Open Access Journals (Sweden)

    Boaz G. Oliveira


    Full Text Available We present a theoretical study of solvent effect on C2H5N···HF hydrogen-bonded complex through the application of the AGOA methodology. By using the TIP4P model to orientate the configuration of water molecules, the hydration clusters generated by AGOA were obtained through the analysis of the molecular electrostatic potential (MEP of solute (C2H5N···HF. Thereby, it was calculated the hydration energies on positive and negative MEP fields, which are maxima (PEMmax and minima (PEMmin when represent the -CH2- methylene groups and hydrofluoric acid, respectively. By taking into account the higher and lower hydration energy values of -370.6 kJ mol-1 and -74.3 kJ mol-1 for PEMmax and PEMmin of the C2H5N···HF, our analysis shows that these results corroborate the open ring reaction of aziridine, in which the preferential attack of water molecules occurs at the methylene groups of this heterocyclic.

  3. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. (United States)

    Knox, R J; Jenkins, T C; Hobbs, S M; Chen, S; Melton, R G; Burke, P J


    A novel prodrug activation system, endogenous in human tumor cells, is described. A latent enzyme-prodrug system is switched on by a simple synthetic, small molecule co-substrate. This ternary system is inactive if any one of the components is absent. CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is an antitumor prodrug that is activated in certain rat tumors via its 4-hydroxylamine derivative to a potent bifunctional alkylating agent. However, human tumor cells are resistant to CB 1954 because they are unable to catalyze this bioactivation efficiently. A human enzyme has been discovered that can activate CB 1954, and it has been shown to be commonly present in human tumor cells. The enzyme is NQO2 [NAD(P)H quinone oxidoreductase 2], but its activity is normally latent, and a nonbiogenic co-substrate such as NRH [nicotinamide riboside (reduced)] is required for enzymatic activity. There is a very large (100-3000-fold) increase in CB 1954 cytotoxicity toward either NQO2-transfected rodent or nontransfected human tumor cell lines in the presence of NRH. Other reduced pyridinium compounds can also act as co-substrates for NQO2. Thus, the simplest quaternary salt of nicotinamide, 1-methyl-3-carboxamidopyridinium iodide, was a co-substrate for NQO2 when reduced to the corresponding 1,4-dihydropyridine derivative. Increased chain length and/or alkyl load at the 1-position of the dihydropyridine ring improved specific activity, and compounds more active than NRH were found. However, little activity was seen with either the 1-benzyl or 1-(2-phenylethyl) derivatives. A negatively charged substituent at the 3-position of the reduced pyridine ring also negated the ability of these compounds to act as cosubstrates for NQO2. In particular, 1-carbamoylmethyl-3-carbamoyl-1,4dihydropyridine was shown to be a co-substrate for NQO2 with greater stability than NRH, with the ability to enter cells and potentiate the cytotoxicity of CB 1954. Furthermore, this agent is synthetically


    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  5. A theoretical study of dihydrogen bonds in small protonated rings: aziridine and azetidine cations. (United States)

    Oliveira, B G; Araújo, R C M U; Carvalho, A B; Ramos, M N


    B3LYP/6-311++G(d,p) calculations were used to predict some molecular properties of the C2H6N+...BeH2, C2H6N...MgH2, C3H8N...BeH2 and C3H8N+...MgH2 dihydrogen-bonded complexes. In these systems, it was demonstrated that the C2H6N+ and C3H8N+ protonated rings are potential candidates to bind with protonic hydrogens derived from alkaline earth metal compounds, BeH2 and MgH2. In terms of structural parameters and quantification of the dihydrogen bond energies, we should mention that the C2H6N+ three-membered ring provides the formation of stronger bound systems, which are 4.0 kJ mol-1 more stables than C3H8N+ four-membered ones. As complement, the analysis of the infrared spectrum indicated that red-shifts and blue-shifts are occurring in the N-H bonds of both C2H6N+ and C3H8N+ cationic rings. However, these two vibrational shifts were also verified on BeH2 and MgH2, what lead us to affirm that cationic compounds derived from small nitrogen rings and earth alkaline molecules are able to form unusual dihydrogen-bonded complexes by means of distinct spectroscopic phenomena, the red-shits and blue-shifts.

  6. Silver(I)-catalyzed dual activation of propargylic alcohol and aziridine/azetidine: triggering ring-opening and endo-selective ring-closing in a cascade. (United States)

    Bera, Milan; Roy, Sujit


    [Ag(COD)(2)]PF(6) catalyzes the reaction between propargyl alcohols and N-tosylaziridines/azetidines leading to a diverse range of N,O-heterocycles, namely, oxazines, oxazepines, and oxazocines via ring-opening and ring-closing in a cascade.

  7. Preparation and property of waterborne nitrocellulose emulsion modified by aziridine crosslinker%氮丙啶交联剂改性水性硝化纤维乳液的制备及性能

    Institute of Scientific and Technical Information of China (English)

    蒋吉磊; 惠媛媛



  8. 硫酸氢季铵盐催化环氧化物和氮杂环丙烷的醇解反应%Alcoholysis of Epoxides and Aziridines Catalyzed by Quaternary Ammonium Bisulfate

    Institute of Scientific and Technical Information of China (English)

    张万轩; 叶康; 刘丽琴; 曹锰




    NARCIS (Netherlands)



    Ephedrine and pseudoephedrine are converted by means of a Mitsunobu reaction to respectively trans- and cis-aziridines, which can be ring-opened at the benzylic center with inversion of configuration by thiols and thiol acids. The trans-aziridine from ephedrine reacts also with H2S in acetone under

  10. Expedite Protocol for Construction of Chiral Regioselectively N-Protected Monosubstituted Piperazine, 1,4-Diazepane, and 1,4-Diazocane Building Blocks

    DEFF Research Database (Denmark)

    Crestey, François; Witt, Matthias; Jaroszewski, Jerzy W.


    This paper describes the first study of solution-phase synthesis of chiral monosubstituted piperazine building blocks from nosylamide-activated aziridines. The protocol, involving aminolysis of the starting aziridines with ω-amino alcohols and subsequent Fukuyama−Mitsunobu cyclization, offers...

  11. Pharmacology of the mixed-function radio- and chemosensitizers CB 1954 and RSU 1069

    Energy Technology Data Exchange (ETDEWEB)

    Workman, P.; Walton, M.I.


    The authors have studied the pharmacokinetics and metabolism in mice of CB 1954 and RSU 1069. Containing both nitro and alkylating (aziridine) substituents, these are lead compounds in the mixed-function analogue series, which show particular promise for sensitizer development. Both compounds are degraded extensively, via pathways including nitro reduction, aziridine ring hydrolysis and aziridine ring removal. RSU 1069 was eliminated more rapidly than CB 1954. Tissue/plasma ratios tended to be rather lower than those for simple nitroimidazoles of intermediate lipophilicity, which are usually close to 100%. Nevertheless, tumor concentrations were consistent with potent sensitization. There is, however, scope for pharmacokinetic fine-tuning to modify tissue penetration as appropriate.

  12. Easy preparation of enantiopure C2 symmetrical hydroxy and amino sulfides derived from ephedrine and their application in a Pd catalyzed coupling reaction

    NARCIS (Netherlands)

    Koning, Bartjan; Hulst, Ron; Kellogg, Richard M.


    Ephedrine can be readily converted by means of intramolecular SN2 substitution by the hydroxyl or amino substituent into, respectively, the corresponding epoxide or aziridine with high stereocontrol. Subsequent stereoselective ring opening at the benzylic centre using tetrabutylammoniumfluoride (TBA

  13. Bifurcated, modular syntheses of chiral annulet triazacyclononanes. (United States)

    Argouarch, Gilles; Stones, Graham; Gibson, Colin L; Kennedy, Alan R; Sherrington, David C


    Three chiral 2,6-disubstituted tri-N-methyl azamacrocycles have been prepared by modular methods. These macrocycles were accessed from three chiral 1,4,7-triazaheptanes intermediates that were prepared by two independent routes. The first of these routes involved the benzylamine opening of chiral tosyl aziridines followed by debenzylation but was problematic on solubility grounds. A second, more effective, route was developed which avoided debenzylation by using ammonia in the nucleophilic opening of chiral tosyl aziridines.

  14. Intramolecular azide to alkene cycloadditions for the construction of pyrrolobenzodiazepines and azetidino-benzodiazepines. (United States)

    Hemming, Karl; Chambers, Christopher S; Jamshaid, Faisal; O'Gorman, Paul A


    The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

  15. Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Karl Hemming


    Full Text Available The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs, pyrrolo[1,2,5]benzothiadiazepines (PBTDs, and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

  16. Application of waterborne acrylic emulsions in coated controlled release fertilizer using reacted layer technology

    Institute of Scientific and Technical Information of China (English)

    Yazhen Shen; Cong Zhao; Jianmin Zhou; Changwen Du


    Waterborne acrylic emulsions modified with organic siloxanes and aziridine crosslinker were synthesized and applied as coating of controlled release fertilizer. The free films were characterized and the nutrient release pro-files of the coated fertilizers were determined. The results show that methyl silicone oil and methylsilanolate so-dium could not improve water resistance performance and glass transition temperature Tg of coatings, while the firmness is enhanced. Aziridine crosslinker improves the water resistance performance, firmness and Tg. Incorpo-ration of methyl silicone oil and aziridine crosslinker gives an excellent aqueous acrylic emulsion for coated con-trol ed release fertilizer, with the 30-day cumulative nutrient release reduced to 16%and an estimated nutrient release duration over 190 days. Therefore, this waterborne coating is promising to meet the requirements for controlled release of nutrient and environmental protection.


    Directory of Open Access Journals (Sweden)

    Assia Keniche


    Full Text Available A new series of aziridines was synthesized in our laboratory, which displays potent antibiotic activities. However, a practical synthesis by using the coupling method of this aziridines with either phosphonate or N-phtaloyl acide moiety can be converted into various derivatives. This work describes new results of our ongoing research targeting new derivatives of biological interest. All the compounds were screened for their antibacterial activity, they all showed comparable moderate to good growth inhibitory activity with reference to Tetracyclin and Gentamicin.

  18. An Approach to Preparation of trans-DHQs via Ring-Opening of meso-N-Sulfonylaziridines

    DEFF Research Database (Denmark)

    Nolsøe, Jens Mortansson Jelstrup; Riegert, David; Müller, Paul;


    As an approach to the enantioselective synthesis of trans-decahydroquinolines (DHQs), desymmetrization of meso-aziridine (5) with various carbon nucleophiles under catalytic conditions was investigated. By applying TMSCN in the presence of YbCl3 and chiral nonracemic ligands, nitrile 13 was obtai...

  19. Stereoselective Addition of Nucleophiles to Aziridinyl-2-carboxaldimine

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Woo; Noh, Heui Yoon; Paek, Seong In; Ha, Hyun Joon [Hankuk University of Foreign Studies, Yongin (Korea, Republic of); Lee, Won Koo [Sogang University, Seoul (Korea, Republic of)


    The addition of various nucleophiles to enantiomerically pure (p-methoxyphenyl)-[1'(R)-α-methylbenzyl] aziridin-2(R)-ylmethylene]amine was successful in highly stereoselective manner to give 2-aminomethylaziridine in the presence of BF{sub 3}·OEt{sub 2}. Commercial success to produce both enantiomers of aziridine-2-carboxylates in optically pure forms prompts us to extend their synthetic utilities for the preparation of enantiopure nitrogen containing molecules. In last few years we have studied with chiral aziridine-2-carboxylates to provide enantiomerically pure α- or β-amino ester and their derivatives. Synthetic study has been extended to construct diamine compounds based on the reaction with the substrate, aziridinyl-2-carboxaldimine. Recently we successfully prepared aminomethylaziridine and 4,5-disubstitued imidazolidin-2-ones by the addition of organomagnesium reagents to aziridinyl-2-carboxaldimine. The additions of alkyl- and arylmagnesium reagents to the chiral [1'(R)-α-methylbenzyl]aziridine-2(R)-carboxaldimine were highly stereoselective in most cases with chelation controlled transition states. The subsequent treatment of theses adducts with triphosgen and NaH afforded enantiopure 5-alkyl- or 5-aryl-4-chloromethylimidazolidin-2-ones.

  20. Effects of the covalent linker groups on the spin transport properties of single nickelocene molecules attached to single-walled carbon nanotubes (United States)

    Wei, Peng; Sun, Lili; Benassi, Enrico; Shen, Ziyong; Sanvito, Stefano; Hou, Shimin


    The understanding of how the spin moment of a magnetic molecule transfers to a carbon nanotube, when the molecule is attached to it, is crucial for designing novel supramolecular spin devices. Here we explore such an issue by modeling the spin transport of a single-walled carbon nanotube grafted with one nickelocene molecule. In particular we investigate how the electron transport becomes spin-polarized depending on the specific linking group bonding nickelocene to the nanotube. We consider as linkers both aziridine and pyrrolidine rings and the amide group. Our calculations show that, at variance with aziridine, both pyrrolidine and amide, do alter the sp2 character of the binding site of the nanotube and thus affect the transmission around the Fermi level. However, only aziridine allows transferring the spin polarization of the nickelocene to the nanotube, whose conductance at the Fermi level becomes spin-polarized. This suggests the superiority of aziridine as a linker for grafting magnetic molecules onto carbon nanotubes with efficient spin filtering functionality.

  1. Synthesis of enantiopure 3-substituted morpholines

    DEFF Research Database (Denmark)

    Bornholdt, Jan; Felding, Jakob; Kristensen, Jesper Langgaard


    Enantiopure 3-substituted morpholines were assembled through ring-opening of a N-2-benzothiazolesulfonyl (Bts) activated aziridine with organocuprates followed by a ring annulation reaction with a vinylsulfonium salt under microwave conditions. Deprotection of the N-Bts group proceeds under very...

  2. Total Synthesis of balanol, Part 2

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Kelly, Nicholas; Tedenborg, Lars


    A convergent enantioselective total synthesis of the natural product (-)-balanol (1) is described. In addition to benzophenone fragment 8, key intermediates are chiral bicyclic aziridine 3 and the corresponding epoxide 4, both of which undergo highly regio- and stereoselective nucleophilic ring-o...

  3. Aminolysis of resin-bound N-nosylaziridine-2-carboxylic acids

    DEFF Research Database (Denmark)

    Olsen, Christian A; Christensen, Caspar; Nielsen, Birgitte;


    [Structure: see text] Solid-phase synthesis is a rapidly developing area of organic chemistry, of particular importance for medicinal chemistry and chemical biology. Aziridines have previously only rarely been applied in solid-phase synthesis. In the present work, aminolysis of resin-bound, spring...

  4. NMR Investigation of the complexation of (S-2-isopropyl- 1-(o-nitrophenylsulfonylaziridine with -cyclodextrin

    Directory of Open Access Journals (Sweden)

    Mohamed Z. Sliman


    Full Text Available Aziridines are known to undergo hydrolysis in the presence of cyclodextrins, whereas the latter are largely investigated as potential vectors of biologically active compounds. Despite this easy cyclodextrin-induced cleavage of aziridines in aqueous medium, it was of interest to find out a model aziridine derivative that would be sufficiently water-stable and form a stable complex with b-cyclodextrin in aqueous medium, so that it could be used as a reference in future formulations or vectorization work. Among compounds we have investigated, we found out that only (S-2-isopropyl-1-(o-nitrophenylsulfonylaziridine complied with the above-mentioned solubility and stability requirements. NMR studies of the inclusion complex of this derivative with b-cyclodextrin provided useful parameters related to the stoichiometry of the complex and the association constant Ka. The geometry of the complex was assessed by 2D-ROESY experiments, suggesting a deep insertion of the aziridine into the cavity of b-cyclodextrin.

  5. Aziridino Alcohols as Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Kornø, Hanne Tøfting; Guijarro, David;


    addition of diethylzinc to benzaldehyde, with up to 90% stereoselectivity. The absolute configuration of the alcohol product is dependent on the substitution pattern of the aziridine ring, and different transition state models are proposed to explain the observed switch in enantioselectivity. The C-2...

  6. Chemistry of phosphorus ylides 31: Reaction of azidocoumarin with active phosphonium ylides, synthesis and antitumour activities of chromenones

    Indian Academy of Sciences (India)

    Soher S Maigali; Mansoura A Abd-El-Maksoud; Fouad M Soliman


    The reaction of 4- azidochromen-2-one (1) with the nucleophilic phosphacumulene ylides 2, 8, and 12 afforded the new heterocyclic triazoles, triazepines, aziridine, pyrrolone containing a coumarin moiety. Cycloaddition reactions took place first to give triazoline 3 and 9. The triazolines rearranged to the triazepines 4, 10, and 13 accompanied by elimination of triphenylphosphine leading to the phosphorus-free triazepines 5, 11, and moreover, aziridine 6 was produced via nitrogen extrusion from the triazoline 3, followed by ring expansion to the pyrrolone 7. On the other hand, the reaction of the azidocoumarin 1 with the phosphallene yield 15 behaves differently and afforded the triazine 17 and azetone 18. The antitumour activity of compounds 3, 4, 6, and 11 was evaluated, in vitro, against (breast: MCF-7 and liver: HPEG2) human solid tumour cell lines. They showed values closed to that recorded by the reference drug doxorubicin.

  7. Palladium-Catalyzed, Enantioselective Heine Reaction. (United States)

    Punk, Molly; Merkley, Charlotte; Kennedy, Katlyn; Morgan, Jeremy B


    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)-diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis.

  8. Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker

    DEFF Research Database (Denmark)

    Crestey, François; Ottesen, Lars Korsgaard; Jaroszewski, Jerzy Witold


    The Letter describes an improved, rapid and mild strategy for the loading of primary alcohols onto a polystyrene trityl resin via a highly reactive trityl bromide linker. This protocol facilitates an efficient resin loading even of acid-sensitive or heat-labile alcohols, which otherwise require...... of a sensitive alcohol containing an activated aziridine functionality, the use of the trityl bromide linker proved superior to a recently described silver triflate-assisted trityl chloride resin-based procedure....

  9. Synthesis and Crystal Structure of a New Salen Complex

    Institute of Scientific and Technical Information of China (English)

    LI Li-Jun; LI Ying; SUN Wen-Hua


    @@ Salen Schiff base complexes are some of the most important stereochemical models in transition metal coordina tion chemistry, with their ease of preparation and structural variation. [1] Salen complexes are extensively used as organic reaction catalysts, it was reported to be used in asymmetric cyclopropanation, epoxidation, aziridination, hydrolysis, alkylation, Diels-Alder reaction, reduction, oxidation etc. Here we report the synthesis and structure of a new salen nickel complex 4.

  10. Bending rigid molecular rods: formation of oligoproline macrocycles. (United States)

    Scully, Conor C G; Rai, Vishal; Poda, Gennadiy; Zaretsky, Serge; Burns, Darcy C; Houliston, R Scott; Lou, Tiantong; Yudin, Andrei K


    Bent but not broken: cyclic oligoprolines are accessed in a reaction that effectively bends rigid oligoproline peptides (see scheme; TBDMS=tert-butyldimethylsilyl). The stitching is accomplished during macrocyclization enabled by aziridine aldehydes and isocyanides. Molecular modeling studies suggest that electrostatic attraction between the termini of the linear peptide is pivotal for macrocyclization. The macrocycles were studied by circular dichroism with a polyproline II structure being observed in larger macrocycles.

  11. Nitrogen Atom Transfer From High Valent Iron Nitrides

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Michael D. [New Mexico State Univ., Las Cruces, NM (United States); Smith, Jeremy M. [Indiana Univ., Bloomington, IN (United States)


    This report describes the synthesis and reactions of high valent iron nitrides. Organonitrogen compounds such as aziridines are useful species for organic synthesis, but there are few efficient methods for their synthesis. Using iron nitrides to catalytically access these species may allow for their synthesis in an energy-and atom-efficient manner. We have developed a new ligand framework to achieve these goals as well as providing a method for inducing previously unknown reactivity.

  12. Dual-function 2-nitroimidazoles as hypoxic cell radiosensitizers and bioreductive cytotoxins: In vivo evaluation in KHT murine sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Cole, S.; Stratford, I.J.; Adams, G.E.; Fielden, E.M.; Jenkins, T.C. (Medical Research Council, Didcot, Oxon (England))


    The efficacies of a series of potential prodrugs of RSU-1069 and its alkyl-aziridine analogues were assessed. These 1-(2-haloethylamino)-3-(2-nitro-1-imidazolyl)-2-propanol compounds were designed to cyclize in vivo to generate 2-nitro-imidazoles with aziridine (RSU-1069) or alkyl-substituted aziridine (RSU-1164, RB-7040, or RSU-1150) functions. Maximum tolerated single, intraperitoneal doses (MTD) were determined in C3H/He mice bearing subcutaneous KHT sarcomas, and a drug dose-response relationship for radiosensitization was established for each compound administered at the optimum time (45-60 min) before local irradiation of tumors with a 10-Gy dose of X-rays. The potentials of the compounds as bioreductive cytotoxins were studied by administering them immediately after irradiation. Tumor cell survival was measured 18-24 h after treatment in an in vitro soft agar clonogenic assay. Results of toxicity, radiosensitization, and bioreductive cytotoxicity assays for each of the prodrugs (RB-6171, RB-6172, RB-6173, RB-6174, and RB-6175) of the alkyl-substituted aziridines were entirely consistent with complete conversion to their respective target compounds. For example, RB-6171 (the prodrug form of RSU-1164) was only about four times less efficient than RSU-1069 as a radiosensitizer and bioreductive cytotoxin but had an MTD 7.5 times higher. In contrast, prodrugs of RSU-1069 (RB-6144 and RB-6145) were two- to threefold less toxic than their expected product. RB-6144 was a poor radiosensitizer and bioreductive agent compared with RSU-1069 and was similar to RB-6170, a nonalkylating nitroimidazole. This is consistent with the observation that there is limited conversion of RB-6144 to RSU-1069 in vitro. However, radiosensitization and bioreductive cytotoxicity produced by RB-6145 were only slightly less than the effects produced by RSU-1069.

  13. Encapsulation and characterization of proton-bound amine homodimers in a water-soluble, self-assembled supramolecular host


    Pluth, Michael D.; Fiedler, Dorothea; Mugridge, Jeffrey S.; Bergman, Robert G.; Raymond, Kenneth N.


    Cyclic amines can be encapsulated in a water-soluble self-assembled supramolecular host upon protonation. The hydrogen-bonding ability of the cyclic amines, as well as the reduced degrees of rotational freedom, allows for the formation of proton-bound homodimers inside of the assembly that are otherwise not observable in aqueous solution. The generality of homodimer formation was explored with small N-alkyl aziridines, azetidines, pyrrolidines, and piperidines. Proton-bound homodimer formatio...

  14. SN2-type ring opening of substituted--tosylaziridines with zinc (II) halides: Control of racemization by quaternary ammonium salt

    Indian Academy of Sciences (India)

    Manas K Ghorai; Deo Prakash Tiwari; Amit Kumar; Kalpataru Das


    Quaternary ammonium salt mediated highly regioselective ring opening of aziridines with zinc(II) halides to racemic and non-racemic -halo amines in excellent yield and selectivity is described. The reaction proceeds via an SN2-type pathway and the partial racemization of the starting substrate and the product was effectively controlled by using quaternary ammonium salts to afford the enantioenriched products (er up to 95:5).

  15. Utilization of N-X bonds in the synthesis of N-heterocycles. (United States)

    Minakata, Satoshi


    Nitrogen-containing heterocycles--such as aziridines, pyrrolidines, piperidines, and oxazolines--frequently show up as substructures in natural products. In addition, some of these species show potent biological activities. Therefore, researchers would like to develop practical and convenient methods for constructing these heterocycles. Among the available methods, the transfer of N(1) units to organic molecules, especially olefins, is a versatile method for the synthesis of N-heterocycles. This Account reviews some of our recent work on the synthesis of N-heterocycles using the N-X bond. A nitrogen-halogen bond bearing an electron-withdrawing group on the nitrogen can be converted to a halonium ion. In the presence of C-C double bonds, these species produce three-membered cyclic halonium intermediates, which can be strong electrophiles and can produce stereocontrolled products. N-Halosuccinimides are representative sources of halonium ions, and the nitrogen of succinimide is rarely used in organic synthesis. If the nitrogen could act as a nucleophile, after releasing halonium ions to C-C double bonds, we expect great advances would be possible in the stereoselective functionalization of olefins. We chose N-chloro-N-sodio-p-toluenesulfonamide (chloramine-T, CT), an inexpensive and commercially available reagent, as our desired reactant. In the presence of a catalytic amount of CuCl or I(2) and AgNO(3), we achieved the direct aziridination of olefins with CT. The reaction catalyzed by I(2) could be carried out in water or silica-water as a green process. The reaction of iodoolefins with CT gave pyrrolidine derivatives under extremely mild conditions with complete stereoselectivity. We also extended the utility of the N-chloro-N-metallo reagent, which is often unstable and difficult to work with. Although CT does not react with electron-deficient olefins without a metal catalyst or an additive, we found that N-chloro-N-sodiocarbamates react with electron

  16. Self-optimisation and model-based design of experiments for developing a C-H activation flow process. (United States)

    Echtermeyer, Alexander; Amar, Yehia; Zakrzewski, Jacek; Lapkin, Alexei


    A recently described C(sp(3))-H activation reaction to synthesise aziridines was used as a model reaction to demonstrate the methodology of developing a process model using model-based design of experiments (MBDoE) and self-optimisation approaches in flow. The two approaches are compared in terms of experimental efficiency. The self-optimisation approach required the least number of experiments to reach the specified objectives of cost and product yield, whereas the MBDoE approach enabled a rapid generation of a process model.

  17. Mass Spectral Fragmentation of (S,S)-N,N′-Bis [1-(hydroxymethyl)alkyl]anthracene/Naphthalene-1,8-dicarboxamides under Electron Impact Ionization Conditions

    Institute of Scientific and Technical Information of China (English)


    The mass spectrometric fragmentation of(S,S)-N,N′-bis[1-(hydroxymethyl)alkyl]anthracene/naphthalene-1,8-dicarboxamides was investigated with the aid of mass-analyzed ion kinetic energy spectrometry and the elemental compositions of important fragment ions were determined by accurate mass measurement under electron impact ionization conditions. All the compounds could eliminate formaldehyde. The [M-CH2O] ions could also eliminate imine, aziridine, aziridinone,2-amonoalkan-1-ol, water, and other fragments. Several cyclizations were observed under electron impact ionization.


    Institute of Scientific and Technical Information of China (English)


    A novel method to prepare crosslinked polyethyleneimine (CPEI) hollow nanospheres was reported.Uniform silica nanospheres were used as templates,3-aminopropyl trimethoxysilane (APS) was immobilized on the surface of silica nanospheres as couple agent.Aziridine was initiated ring-opening polymerization with the amino groups in APS to form polyethyleneimine (PEI) shell layer.1,4-Butanediol diacrylate was utilized to crosslink PEI polymeric shell.The silica nanospheres in core were etched by hydrofluoric acid to obtain hollow CPEI nanospheres.The hollow nanospheres were characterized by X-ray photoelectron spectroscopy (XPS),transmission electron microscopy (TEM),and thermogravimetric analysis (TGA).

  19. Functional-Group-Tolerant, Silver-Catalyzed N-N Bond Formation by Nitrene Transfer to Amines. (United States)

    Maestre, Lourdes; Dorel, Ruth; Pablo, Óscar; Escofet, Imma; Sameera, W M C; Álvarez, Eleuterio; Maseras, Feliu; Díaz-Requejo, M Mar; Echavarren, Antonio M; Pérez, Pedro J


    Silver(I) promotes the highly chemoselective N-amidation of tertiary amines under catalytic conditions to form aminimides by nitrene transfer from PhI═NTs. Remarkably, this transformation proceeds in a selective manner in the presence of olefins and other functional groups without formation of the commonly observed aziridines or C-H insertion products. The methodology can be applied not only to rather simple tertiary amines but also to complex natural molecules such as brucine or quinine, where the products derived from N-N bond formation were exclusively formed. Theoretical mechanistic studies have shown that this selective N-amidation reaction proceeds through triplet silver nitrenes.

  20. 5-Azido-4-dimethylamino-1-methyl-1,2,4-triazolium Hexafluoridophosphate and Derivatives

    Directory of Open Access Journals (Sweden)

    Gerhard Laus


    Full Text Available 5-Azido-4-(dimethylamino-1-methyl-1,2,4-triazolium hexafluoridophosphate was synthesized from the corresponding 5-bromo compound with NaN3. Reaction with bicyclo[2.2.1]hept-2-ene yielded a tricyclic aziridine, addition of an N-heterocyclic carbene resulted in a triazatrimethine cyanine, and reduction with triphenylphosphane gave the 5-amino derivative. The crystal structures of three nitrogen-rich salts were determined. Thermoanalysis of the cationic azide and triazene showed exothermal decomposition. The triazene exhibited negative solvatochromism in polar solvents involving the dipolarity π* and hydrogen-bond donor acidity α of the solvent.

  1. Methodologies for chemical utilization of C02 to valuable compounds through molecular activation by efficient catalysts

    Institute of Scientific and Technical Information of China (English)

    Liangnian HE; Ya DU; Chengxia MIAO; Jinquan WANG; Xiaoyong DOU; Ying WU


    The reactions of CO2 with oxirane to produce cyclic carbonate, and with aziridine to afford oxazolidine have been of interest as a useful method for its fixation by a chemical process. Highly efficient processes employing recyclable CO2-phlilic homogeneous catalyst were devised for environmentally benign synthesis of cyclic carbonates and oxazolidinones under supercritical CO2 without any organic solvent. These processes represent pathways for greener chemical fixations of CO2 to afford industrial useful materials such as organic carbonates and oxazolidinones with great potential applications.

  2. Cycloaddition of methyl 2-(2,6-dichorophenyl)-2H-azirine-3-carboxylate to electron rich 2-azadienes


    Alves, M. José; Durães, M. Miguel; Fortes, A. Gil


    Tert-Butyldimethylsililoxy-2-aza-1,3-butadienes react with 2H-azirine 3 leading to Diels-Alder cycloadducts in moderate yields. The reactions are endo- and regio- selective with the azirine being added by its less hindered face. There is only one product in the case of 1b, 4b. There are two isomers (4 and 5) from 1a, 1c and 1d. A different result was obtained with the diene 1e. Diene 1e formed products 4e and 8. Some of compounds 4 and 5 have been hydrolysed leading to functionalized aziridin...

  3. Effect of support structure on CO2 adsorption properties of pore-expanded hyperbranched aminosilicas

    KAUST Repository

    Drese, Jeffrey H.


    Hyperbranched aminosilica (HAS) CO 2 adsorbents are prepared by the ring-opening polymerization of aziridine from SBA-15 mesoporous silica, as in the original synthesis of HAS materials, as well as over an array of new support materials with substantially larger average pore diameters to elucidate the effect of support porosity on final adsorbent properties. Pore-expanded hyperbranched aminosilica (PEHAS) CO 2 adsorbents are prepared from several different pore-expanded, ordered mesoporous silicas including pore-expanded SBA-15, mesocellular foam, and a large-pore commercial silica. The effect of the nature of the silica support is determined by examining the degree of aziridine polymerization and the CO 2 adsorption kinetics and capacities of the resulting organic/inorganic hybrid materials. Comparisons are made to non-pore-expanded SBA-15 based HAS adsorbents, reported previously, where pores become blocked at higher amine loadings. The PEHAS materials unexpectedly possess lower amine loadings than the previously reported HAS materials and do not exhibit pore blocking. The use of acetic acid as a catalyst during PEHAS synthesis only marginally increases amine loading. The adsorption kinetics of PEHAS adsorbents are similar to HAS adsorbents with low amine loadings and do not show the detrimental effects of pore-blocking. However, the inability to synthesize PEHAS adsorbents with high amine loadings via this approach limits the total amount of CO 2 captured per gram of material, compared to HAS adsorbents with high amine loadings. © 2011 Elsevier Inc. All rights reserved.

  4. Crosslinked and Dyed Chitosan Fiber Presenting Enhanced Acid Resistance and Bioactivities

    Directory of Open Access Journals (Sweden)

    Xiao-Qiong Li


    Full Text Available The application of biodegradable chitosan fiber for healthy and hygienic textiles is limited due to its poor acid resistance in wet processing and poor antioxidant activity. In order to prepare chitosan fiber with good acid resistance and high antioxidant activity, chitosan fiber was first crosslinked by a water-soluble aziridine crosslinker, and then dyed with natural lac dye consisting of polyphenolic anthraquinone compounds. The main application conditions and crosslinking mechanism of the aziridine crosslinker, the adsorption mechanism and building-up property of lac dye on the crosslinked fiber, and the effects of crosslinking and dyeing on the antioxidant and antibacterial activities of chitosan fiber were studied. The crosslinked fiber exhibited greatly reduced weight loss in acidic solution, and possessed excellent acid resistance. Lac dye displayed a very high adsorption capability on the crosslinked fiber and a high utilization rate under weakly acidic medium. The Langmuir–Nernst isotherm was the best model to describe the adsorption behavior of lac dye, and Langmuir adsorption had great contribution to total adsorption. Lac dyeing imparted good antioxidant activity to chitosan fiber. Crosslinking and dyeing had no impact on the good inherent antibacterial activity of chitosan fiber.

  5. Rational Design of Push-Pull Fluorene Dyes: Synthesis and Structure-Photophysics Relationship. (United States)

    Shaya, Janah; Fontaine-Vive, Fabien; Michel, Benoît Y; Burger, Alain


    Our work surveyed experimental and theoretical investigations to construct highly emissive D-π-A (D=donor, A=acceptor) fluorenes. The synthetic routes were optimised to be concise and gram-scalable. The molecular design was first rationalised by varying the electron-withdrawing group from an aldehyde, ketotriazole or succinyl to methylenemalonitrile or benzothiadiazole. The electron-donating group was next varied from aliphatic or aromatic amines to saturated cyclic amines ranging from aziridine to azepane. Spectroscopic studies correlated with TD-DFT calculations provided the optimised structures. The selected push-pull dyes exhibited visible absorptions, significant brightness, important solvatofluorochromism, mega-Stokes shifts (>250 nm) and dramatic shifts in emission to the near-infrared. The current library includes the comprehensive characterization of 16 prospective dyes for fluorescence applications. Among them, several fluorene derivatives bearing different conjugation anchors were tested for coupling and demonstrated to preserve the photophysical responses once further bound.

  6. Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics. (United States)

    Low, Kristin E; Ler, Spencer; Chen, Kevin J; Campbell, Robert L; Hickey, Jennifer L; Tan, Joanne; Scully, Conor C G; Davies, Peter L; Yudin, Andrei K; Zaretsky, Serge


    Our previously reported structures of calpain bound to its endogenous inhibitor calpastatin have motivated the use of aziridine aldehyde-mediated peptide macrocyclization toward the design of cyclic peptides and peptidomimetics as calpain inhibitors. Inspired by nature's hint that a β-turn loop within calpastatin forms a broad interaction around calpain's active site cysteine, we have constructed and tested a library of 45 peptidic compounds based on this loop sequence. Four molecules have shown reproducibly low micromolar inhibition of calpain-2. Further systematic sequence changes led to the development of probes that displayed increased potency and specificity of inhibition against calpain over other cysteine proteases. Calculated Ki values were in the low micromolar range, rivaling other peptidomimetic calpain inhibitors and presenting an improved selectivity profile against other therapeutically relevant proteases. Competitive and mixed inhibition against calpain-2 was observed, and an allosteric inhibition site on the enzyme was identified for a noncompetitive inhibitor.

  7. Anisotropy effect of three-membered rings in (1)H NMR spectra: quantification by TSNMRS and assignment of the stereochemistry. (United States)

    Kleinpeter, Erich; Krüger, Stefanie; Koch, Andreas


    The spatial magnetic properties (through space NMR shieldings, TSNMRSs) of cyclopropane; of the heteroanalogous oxirane, thiirane, and aziridine; and of various substituted mono-, dis-, and tris-cyclic analogues have been computed by the GIAO perturbation method employing the nucleus independent chemical shift (NICS) concept and visualized as iso-chemical-shielding surfaces (ICSSs) of various size and direction. The TSNMRS values, thus obtained, can be employed to visualize the anisotropy (ring current) effect of the cyclopropane ring moiety. This approach has been employed to qualify and quantify substituent influences and contributions of appropriate ring heteroatoms O, NH, and S on the anisotropy (ring current) effect of three-membered ring moieties, and to assign the stereochemistry of mono-, bis-, and tris-cyclic structures containing cyclopropane as a structural element. Characteristic examples are included.

  8. Improving the tensile strength of carbon nanotube yarn via one-step double [2+1] cycloadditions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, HeeJin [Kyungpook National University, Daegu (Korea, Republic of); Lee, Jaegeun; Park, Byungrak; Sa, Jeong Hoon; Jung, Alum; Kim, Teawon; Park, Junbeom; Hwang, Woonbong; Lee, Kun Hong [Pohang University of Science and Technology, Pohang (Korea, Republic of)


    The tensile strength of a CNT yarn was improved through simple one-step double [2+1] cycloaddition reactions that crosslinked the constituent CNTs using a polyethylene glycol (PEG)-diazide crosslinker. The FT-IR spectrum confirmed that the azide groups in the PEG-diazide were converted into aziridine rings, indicating that the cycloaddition reaction was successful. The generation of crosslinked CNTs was also supported by the observation of N1s peak in the XPS spectrum and the increased thermal stability of the material, as observed by TGA. The tensile strength of the CNT yarn was increased from 0.2GPa to 1.4GPa after the crosslinking reaction when twisted at 4000 twists/ meter. The appropriate selection of the crosslinker may further optimize the CNT yarn crosslinking reaction. The simplicity of this one-step crosslinking reaction provides an economical approach to the mass production of high-strength CNT yarns.

  9. Activation of carboxylic acids in asymmetric organocatalysis. (United States)

    Monaco, Mattia Riccardo; Poladura, Belén; Diaz de Los Bernardos, Miriam; Leutzsch, Markus; Goddard, Richard; List, Benjamin


    Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. Its success relies to a large extent upon the introduction of novel and generic activation modes. Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition-metal catalysis, a general and well-defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self-assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine-opening reaction with carboxylic acids as nucleophiles.

  10. A New Approach to Non-Coordinating Anions: Lewis Acid Enhancement of Porphyrin Metal Centers in a Zwitterionic Metal$-$Organic Framework

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jacob A. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Petersen, Brenna M. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Kormos, Attila [Hungarian Academy of Sciences, Budapest (Hungary); Echeverría, Elena [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Physics and Astronomy; Chen, Yu-Sheng [Univ. of Chicago, Argonne, IL (United States). ChemMatCARS, Center for Advanced Radiation Sources; Zhang, Jian [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry


    Here, we describe a new strategy to generate non-coordinating anions using zwitterionic metal–organic frameworks (MOFs). By assembly of anionic inorganic secondary building blocks (SBUs) ([In(CO2)4]$-$) with cationic metalloporphyrin-based organic linkers, we prepared zwitterionic MOFs in which the complete internal charge separation effectively prevents the potential binding of the counteranion to the cationic metal center. We demonstrate the enhanced Lewis acidity of MnIII- and FeIII-porphyrins in the zwitterionic MOFs in three representative electrocyclization reactions: [2 + 1] cycloisomerization of enynes, [3 + 2] cycloaddition of aziridines and alkenes, and [4 + 2] hetero-Diels–Alder cycloaddition of aldehydes with dienes. Lastly, this work paves a new way to design functional MOFs for tunable chemical catalysis.

  11. Ring-opening of cis-3-Substituted-2-vinylaziridines with Heteroatom Nucleophiles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gaeun; Shin, Miri; Kang, Hanyoung [Chungbuk National Univ., Cheongju (Korea, Republic of)


    The results of the ring opening reaction of N-protected-cis-2-vinyl-3-(benzyloxymethyl)aziridines as model compounds for cis-3-substituted-2-vinylaziridines with various heteroatom nucleophiles are summarized in Table 1. Methanol is a good nucleophile to provide the desired 1,2-amino-alcohol derivative as a single product in excellent yield. We analyzed briefly the effect of solvents with methanol. Although other solvents such as DMF and THF also gave the product, CH{sub 2}Cl{sub 2} was employed as a preferred solvent because of the high yield and ease of handling. All the reactions were, therefore, examined in CH{sub 2}Cl{sub 2} in the presence of BF{sub 3}·OEt{sub 2} as a Lewis acid unless mentioned otherwise. All alcohols behaved as good nucleophiles to exclusively give the desired products (entry 1-7)

  12. Computational synthesis of C₆₀ cyano- and azopolyderivatives. (United States)

    Sheka, Elena F


    The cyanation of C(60) to C(60)(CN)(18) and the aziridination of C(60) to C(60)(NH)(9) were studied by an unrestricted broken spin symmetry Hartree-Fock approach implemented in semiempirical codes based on the AM1 technique. The calculations focused on the successive addition of CN and NH moieties to the fullerene cage following the identification of the target cage atoms as those with the highest atomic chemical susceptibilities calculated at each step. The results obtained were analyzed from the viewpoint of the parallelism between these derivatives as well as C(60) fluorides and hydrides. The difference between the first-stage C(60) chlorination and other sterically free processes is discussed.

  13. An easy stereoselective access to beta,gamma-aziridino alpha-amino ester derivatives via mannich reaction of benzophenone imines of glycine esters with N-sulfonyl alpha-chloroaldimines. (United States)

    Kiss, Loránd; Mangelinckx, Sven; Sillanpää, Reijo; Fülöp, Ferenc; De Kimpe, Norbert


    Mannich-type addition of benzophenone imine glycinates across newly synthesized N-(p-toluenesulfonyl) alpha-chloroaldimines afforded gamma-chloro-alpha,beta-diamino ester derivatives with moderate diastereoselectivity as separable mixtures of anti and syn diastereomers. The gamma-chloro-alpha,beta-diamino esters were efficiently cyclized under basic conditions to the corresponding beta,gamma-aziridino alpha-amino ester derivatives, representing a new class of conformationally constrained heterocyclic alpha,beta-diamino acid derivatives. The relative configuration of the aziridines was determined via X-ray diffraction analysis. Mechanisms and intermediate transition states to explain the stereochemical outcome of the Mannich reaction with different substrates or under different conditions are proposed. The synthetic importance of the beta,gamma-aziridino alpha-amino ester derivatives is demonstrated by their conversion into the corresponding Boc-protected derivatives and ring opening reactions to alpha,beta-diamino esters and a gamma-amino alpha,beta-unsaturated amino ester.

  14. Steady-state and laser flash photolysis studies of 1-aziridinyl-1,2-dibenzoylalkenes

    Energy Technology Data Exchange (ETDEWEB)

    Barik, R.; Kumar, C.V.; Das, P.K.; George, M.V.


    Results of a photochemical study based on product analysis and 337.1-nm laser flash photolysis are reported for several cis- and trans-1,2-dibenzoylethylenes bearing aziridinyl groups at the 1-position. Products isolated from steady-state photolysis suggest facile ring expansions yielding pyrrolines as well as extrusion of alkenes from the aziridine moieties forming nitrene fragments, which subsequently undergo ring closure to give isoxazoles. Laser flash photolysis studies show transient absorption changes, explainable in terms of cis-trans photoisomerization and formation of azomethine ylides. The latter are also observed upon steady-state irradiation of these aziridinyl-1,2-dibenzoylethylenes in an EPA glass at 77 K. 46 references, 4 figures.

  15. The nature of chemical innovation: new enzymes by evolution. (United States)

    Arnold, Frances H


    I describe how we direct the evolution of non-natural enzyme activities, using chemical intuition and information on structure and mechanism to guide us to the most promising reaction/enzyme systems. With synthetic reagents to generate new reactive intermediates and just a few amino acid substitutions to tune the active site, a cytochrome P450 can catalyze a variety of carbene and nitrene transfer reactions. The cyclopropanation, N-H insertion, C-H amination, sulfimidation, and aziridination reactions now demonstrated are all well known in chemical catalysis but have no counterparts in nature. The new enzymes are fully genetically encoded, assemble and function inside of cells, and can be optimized for different substrates, activities, and selectivities. We are learning how to use nature's innovation mechanisms to marry some of the synthetic chemists' favorite transformations with the exquisite selectivity and tunability of enzymes.

  16. Mass spectrometric studies of cis- and trans-1a,3-disubstituted-1,1-dichloro-4-formyl-1a, 2,3,4-tetrahydro-1H-azirino [ 1,2-a ][ 1,5 ] benzodiazepines

    Institute of Scientific and Technical Information of China (English)

    XU, Jia-Xi(许家喜); ZHANG, Xin-Yu(张新宇); JIN, Sheng(金声)


    The mass spectrometric behaviour of four cis- and trans-1a,3- disubstituted -1,1 - dichloro-4-formyl-1a,2,3,4-tetrahydro1H-azirino[1,2-a] [1,5] benzodiazepines has been studied with the aid of mass-analysed ion kinetic energy spectrometry and exact mass measurements under electron impact ionization. All compounds show a tendency to eliminate a chlorine atom from the aziridine ring, and then eliminate a neutral propene or styrene from the diazepine ring to yield azirino[1,2-b][1,3]benzimidazole ions. These azirino[1,2-a] [1,5]-benzodiazepines can also eliminate HCl, or Cl plus HCl simultaneously to undergo a ring enlargement rearrangement to yield 1,6-benzodiazocine ions, which further lose small molecular fragments, propyne or phenylacetylene, with rearrangement to give quinoxaline ions.

  17. Crystal structure of [2-(triethylammonioethyl][(2,4,6-triisopropylphenylsulfonyl]amide tetrahydrate

    Directory of Open Access Journals (Sweden)

    C. Golz


    Full Text Available The zwitterionic title compound, C23H42N2O2S·4H2O, crystallized as a tetrahydrate from a solution of N-[(2,4,6-triisopropylphenylsulfonyl]aziridine in triethylamine, diethyl ether and pentane in the presence of moist air. It is formed by a nucleophillic ring-opening that is assumed to be reversible. The molecular structure shows a major disorder of the triisopropylphenyl group over two equally occupied locations. An interesting feature is the uncommon hydrate structure, exhibiting a tape-like motif which can be classified as a transition of the one-dimensional T4(26(2 motif into the two-dimensional L4(65(76(8 motif.

  18. Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate (United States)

    Li, Jing; Cisar, Justin S.; Zhou, Cong-Ying; Vera, Brunilda; Williams, Howard; Rodríguez, Abimael D.; Cravatt, Benjamin F.; Romo, Daniel


    Natural products have a venerable history of, and enduring potential for the discovery of useful biological activity. To fully exploit this, the development of chemical methodology that can functionalize unique sites within these complex structures is highly desirable. Here, we describe the use of rhodium(II)-catalysed C-H amination reactions developed by Du Bois to carry out simultaneous structure-activity relationship studies and arming (alkynylation) of natural products at ‘unfunctionalized’ positions. Allylic and benzylic C-H bonds in the natural products undergo amination while olefins undergo aziridination, and tertiary amine-containing natural products are converted to amidines by a C-H amination-oxidation sequence or to hydrazine sulfamate zwitterions by an unusual N-amination. The alkynylated derivatives are ready for conversion into cellular probes that can be used for mechanism-of-action studies. Chemo- and site-selectivity was studied with a diverse library of natural products. For one of these—the marine-derived anticancer diterpene, eupalmerin acetate—quantitative proteome profiling led to the identification of several protein targets in HL-60 cells, suggesting a polypharmacological mode of action.

  19. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility. (United States)

    Williams, Elsie M; Little, Rory F; Mowday, Alexandra M; Rich, Michelle H; Chan-Hyams, Jasmine V E; Copp, Janine N; Smaill, Jeff B; Patterson, Adam V; Ackerley, David F


    This review examines the vast catalytic and therapeutic potential offered by type I (i.e. oxygen-insensitive) nitroreductase enzymes in partnership with nitroaromatic prodrugs, with particular focus on gene-directed enzyme prodrug therapy (GDEPT; a form of cancer gene therapy). Important first indications of this potential were demonstrated over 20 years ago, for the enzyme-prodrug pairing of Escherichia coli NfsB and CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. However, it has become apparent that both the enzyme and the prodrug in this prototypical pairing have limitations that have impeded their clinical progression. Recently, substantial advances have been made in the biodiscovery and engineering of superior nitroreductase variants, in particular development of elegant high-throughput screening capabilities to enable optimization of desirable activities via directed evolution. These advances in enzymology have been paralleled by advances in medicinal chemistry, leading to the development of second- and third-generation nitroaromatic prodrugs that offer substantial advantages over CB1954 for nitroreductase GDEPT, including greater dose-potency and enhanced ability of the activated metabolite(s) to exhibit a local bystander effect. In addition to forging substantial progress towards future clinical trials, this research is supporting other fields, most notably the development and improvement of targeted cellular ablation capabilities in small animal models, such as zebrafish, to enable cell-specific physiology or regeneration studies.

  20. Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

    Directory of Open Access Journals (Sweden)

    Nikolai V. Rostovskii


    Full Text Available Strained azirinium ylides derived from 2H-azirines and α-diazoketones under Rh(II-catalysis can undergo either irreversible ring opening across the N–C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methylketene generated from 3-diazoacetylacetone under Rh(II catalysis to give 4,6-dioxa-1-azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p, the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methylketene followed by aziridine ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines.

  1. Synthesis and Crystal Structure of 2,3-Dihydroxymethyl-N-cyclohexylaziridine

    Institute of Scientific and Technical Information of China (English)

    GUO Jin-Bo; YU Zhao-Lian; LI Sen-Lan; CHEN Qing-Hua


    The title compound, 2(S),3(R)-dihydroxymethyl-N-cyclohexylaziridine 1, has been synthesized via tandem Micheal addition and internal nucleophilic substitution reactions of 5-methoxy-3-bromo-2(5H)-furanones 2 with cyclohexylamine 3 and subsequent reduction of intermediate 5, Its crystal structure was determined by single-crystal X-ray diffraction.Crystal data:C1oH19NO2, Mr = 185.26, monoclinic system, space group P21/n, a = 8.0620(16), b = 7.2013(14), c = 18.555(4)(。A), β= 102.30(3)°, V= 1052.5(4)(。A)3, Z= 4, Dc= 1.169 g/cm3, ~MoKα) = 0.071073 nm,μ = 0.080 mm- 1 and F(000) = 408.The structure was refined to R = 0.0439 and wR = 0.1178 for 1839 observed reflections (I > 2σ(I)).The crystallographic structure of 1 shows that the functionalized aziridine ring links two hyroxymethyl groups.

  2. Ruthenium complexes with chiral tetradentate PNNP ligands: asymmetric catalysis from the viewpoint of inorganic chemistry. (United States)

    Mezzetti, Antonio


    This is a personal account of the application of ruthenium complexes containing chiral tetradentate ligands with a P(2)N(2) ligand set (PNNP) as catalyst precursors for enantioselective "atom transfer" reactions. Therewith are meant reactions that involve bond formation between a metal-coordinated molecule and a free reagent. The reactive fragment (e.g. carbene) is transferred either from the metal to the non-coordinated substrate (e.g. olefin) or from the free reagent (e.g. F(+)) to the metal-bound substrate (e.g.beta-ketoester), depending on the class of catalyst (monocationic, Class A; or dicationic, Class B). The monocationic five-coordinate species [RuCl(PNNP)](+) and the six-coordinate complexes [RuCl(L)(PNNP)](+) (L = Et(2)O, H(2)O) of Class A catalyse asymmetric epoxidation, cyclopropanation (carbene transfer from the metal to the free olefin), and imine aziridination. Alternatively, the dicationic complexes [Ru(L-L)(PNNP)](2+) (Class B), which contain substrates that act as neutral bidentate ligands L-L (e.g., beta-ketoesters), catalyse Michael addition, electrophilic fluorination, and hydroxylation reactions. Additionally, unsaturated beta-ketoesters form dicationic complexes of Class B that catalyse Diels-Alder reactions with acyclic dienes to produce tetrahydro-1-indanones and estrone derivatives. Excellent enantioselectivity has been achieved in several of the catalytic reactions mentioned above. The study of key reaction intermediates (both in the solid state and in solution) has revealed significant mechanistic aspects of the catalytic reactions.

  3. Synthesis and Antibacterial Activities of Novel 4-Hydroxy-7-hydroxy- and 3-Carboxycoumarin Derivatives

    Directory of Open Access Journals (Sweden)

    Lin-Wen Lee


    Full Text Available Coumarin derivatives are used as fluorescent dyes and medicines. They also have some notable physiological effects, including the acute hepatoxicity and carcinogenicity of certain aflatoxins, the anticoagulant action of dicoumarol, and the antibiotic activity of novobicin and coumerymycin A1. Because the number of drug resistant strains is increasing at present, the synthesis of new antibacterial compounds is one of the critical methods for treating infectious diseases. Therefore, a series of coumarin-substituted derivatives, namely 4-hydroxy- and 7-hydroxycoumarins, and 3-carboxycoumarins were synthesized. 4-Hydroxycoumarin derivatives 4a–c underwent rearrangement reactions. Both 4- and 7-hydroxycoumarins were treated with activated aziridines which produced series of ring-opened products 7, 8, 10, and 11. 3-Carboxy-coumarin amide dimer derivatives 14–21 were prepared by reacting aliphatic alkylamines and alkyldiamines with PyBOP and DIEA. In this study, we use a new technique called modified micro-plate antibiotic susceptibility test method (MMAST, which is more convenient, more efficient, and more accurate than previous methods and only a small amount of the sample is required for the test. Some of the compounds were produced by reactions with acid anhydrides and demonstrated the ability to inhibit Gram-positive microorganisms. The dimer derivatives displayed lower antibacterial activities.

  4. Thermoset elastomers derived from carvomenthide. (United States)

    Yang, Jinyoung; Lee, Sangjun; Choi, Woo Jin; Seo, Howon; Kim, Pilhan; Kim, Geon-Joong; Kim, Young-Wun; Shin, Jihoon


    Renewable thermoset elastomers were prepared using the plant-based monomer carvomenthide. Controlled ring-opening transesterification polymerization of carvomenthide using diethylene glycol as an initiator gave α,ω-dihydroxyl poly(carvomenthide) (HO-PCM-OH), which was subsequently converted to carboxy-telechelic poly(carvomenthide) (HOOC-PCM-COOH) by esterification with excess succinic anhydride through a one-pot, two-step process, leading to no crystallinity, high viscosity, strong thermal resistance, and low glass transition temperature of the resulting functionalized polyester. Thermal curing processes of the resulting 3, 6, and 12 kg mol(-1) prepolymers were achieved with trifunctional aziridine to give cross-linked PCM elastomers. The thermal properties, mechanical behavior, and biocompatibility of the rubbery thermoset products were investigated by differential scanning calorimetry, thermal gravimetric analysis, dynamic mechanical analysis, tensile tests under static and cyclic loads, and cell adherence. These new materials are useful candidates to satisfy the design objective for the engineering of a variety of soft tissues.

  5. A structural insight into the P1S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

    Energy Technology Data Exchange (ETDEWEB)

    Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata; Nocek, Bogusław; Joachimiak, Andrzej; Mucha, Artur


    N0 -substituted 1,2-diaminoethylphosphonic acids and 1,2-diaminoethylphosphinic dipeptides were explored to unveil the structural context of the unexpected selectivity of these inhibitors of M1 alanine aminopeptidases (APNs) versus M17 leucine aminopeptidase (LAP). The diaminophosphonic acids were obtained via aziridines in an improved synthetic procedure that was further expanded for the phosphinic pseudodipeptide system. The inhibitory activity, measured for three M1 and one M17 metalloaminopeptidases of different sources (bacterial, human and porcine), revealed several potent compounds (e.g., Ki ¼ 65 nM of 1u for HsAPN). Two structures of an M1 representative (APN from Neisseria meningitidis) in complex with N-benzyl-1,2-diaminoethylphosphonic acid and N-cyclohexyl-1,2- diaminoethylphosphonic acid were determined by the X-ray crystallography. The analysis of these structures and the models of the phosphonic acid complexes of the human ortholog provided an insight into the role of the additional amino group and the hydrophobic substituents of the ligands within the S1 active site region.

  6. Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension. (United States)

    Zhu, Gui-Dong; Gandhi, Viraj B; Gong, Jianchun; Thomas, Sheela; Woods, Keith W; Song, Xiaohong; Li, Tongmei; Diebold, R Bruce; Luo, Yan; Liu, Xuesong; Guan, Ran; Klinghofer, Vered; Johnson, Eric F; Bouska, Jennifer; Olson, Amanda; Marsh, Kennan C; Stoll, Vincent S; Mamo, Mulugeta; Polakowski, James; Campbell, Thomas J; Martin, Ruth L; Gintant, Gary A; Penning, Thomas D; Li, Qun; Rosenberg, Saul H; Giranda, Vincent L


    Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.

  7. 4-[4-(4-Fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide–4-[3-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide (0.6/0.4

    Directory of Open Access Journals (Sweden)

    Simona Margutti


    Full Text Available The crystal structure of the title compound, C16H16FN2O2+·I−, was determined as part of a study of the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK inhibitors. The X-ray crystal structure of 4-[4-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide showed the presence of the regioisomer 4-[3-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide. The synthesis of the former compound was achieved by reacting 4-(4-fluorophenyl-3-(4-pyridylisoxazol-5(2H-one after treatment with Et3N in dimethylformamide, with iodomethane. The unexpected formation of the regioisomer could be explained by a rearrangement occurring via aziridine of the isoxazolone compound. The regioisomers have site occupancies of 0.632 (4/0.368 (4. The two six members rings make a dihedral angle of 66.8 (2°.

  8. HTPB/ADN推进剂反应气孔产生机理研究%Reaction Mechanism of Forming Pore in HTPB/AND Propellants

    Institute of Scientific and Technical Information of China (English)

    胥会祥; 庞维强; 李勇宏; 张楠楠; 王晓红


    为揭示HTPB/ADN/AP/Al推进剂产生气孔的原因,制备了一系列含ADN和TEA、T-313、MAPO、HX-752等键合剂的推进剂样品,试验确定与ADN反应产生气孔的组分,并通过DSC/TG-IR/MS联用仪分析了产生气孔的反应机理.结果表明,含固化剂TDI、IPDI和醇胺类键合剂TEA、T-313的推进剂样品不产生气孔,而含氮丙啶类键合剂MAPO、HX-752的样品固化后均出现气孔.DSC法证实MAPO与ADN产生强烈的作用,使ADN的主要放热分解峰温度降低99.7 ℃.在50 ℃,MAPO与ADN混合物(质量比1:1)加热2 h的过程形成了气体产物: N_2O、NO_2,并通过质谱检测到其存在.分析认为,推进剂中氮丙啶类键合剂促使了ADN的分解,形成反应气孔.%In order to reveal the reasons of forming pore in hydroxyl terminated polybutadiene/ammonium dinitramide/ammonium perchlorate/aluminium ( HTPB/ADN/AP/Al ) composite propellants, a series of propellant samples containing ADN and triethanolamine ( TEA ) , triethanolamine trifluoroboron complex ( T-313), tris ( 2-methylaziridinyl) phosphine oxide ( MAPO ) , isoph-thaloyl-bis-(2-methylaziridine) (HX-752) were prepared,and the components of reacting with ADN and forming pore were confirmed, and the reaction mechanism was analyzed by DSC/TG-IR/MS. Results show that there are no pores in the propellant samples containing curing agents such as toluene diisocyanate(TDI) ,isophrone diisocyanate(IPDI) and ethanolamine bonding agents such as TEA, T-313 respectively, but the pores are formed in the samples containing aziridine bonding agents MAPO and HX-752. It is proved by DSC that there is a strong interaction between ADN and MAPO,which decreases the temperature of the main decomposition peak of ADN by about 99.7 ℃ . When the mixture of ADN and MAPO ( mass ratio 1:1) was heated continuously at 50 ℃ for 2 h ,the gasous products N_2O and NO_2 are farmed and detected by mass spectrum. It is considered that the aziridine bonding agents can accelerate

  9. Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes.

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    Daniela Herrera Moro Chao

    Full Text Available Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA. In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2 of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia.

  10. Sustained Release of Mitomycin C from Its Conjugate with Single-Walled Carbon Nanotubes Associated by Pegylated Peptide. (United States)

    Ohta, Takahisa; Hashida, Yasuhiko; Yamashita, Fumiyoshi; Hashida, Mitsuru


    A novel sustained release formulation of mitomycin C (MMC) was developed by employing single-walled carbon nanotubes (SWCNTs) wrapped by designed peptide with polyethylene glycol (PEG) modification (pegylation) as a nano-scale molecular platform. The amino groups of polycationic and amphiphilic H-(-Cys-Trp-Lys-Gly-)(-Lys-Trp-Lys-Gly-)6-OH [CWKG(KWKG)6] peptide associated with SWCNTs were modified using PEG with 12 units (PEG12) to improve the dispersion stability of the composite. Then thiol groups of peptide were conjugated with MMC using N-ε-maleimidocaproic acid (EMCA) as a linker via transformation of aziridine group of MMC. The obtained SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC composites particularly that with 13.6% PEG modification extent of amino groups, showed good dispersion stability both in water and in a cell culture medium for 24 h. The release of MMC from SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC was confirmed to follow first-order kinetics being accelerated by the pH increase in good agreement with the results observed for MMC-dextran conjugate with the same conjugation structure. The SWCNTs-CWKG(KWKG)6-(PEG)12 composite exhibited a considerably low cytotoxicity against cultured human lung adenocarcinoma epithelial cell line (A549). In contrast, SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC demonstrated delayed but relatively corresponding antitumor activity with free MMC at the same concentration. The results suggested the potential role of SWCNTs-CWKG(KWKG)6-(PEG)12 as a carrier for a controlled release drug delivery system (DDS).

  11. Synthesis and Antitumor Evaluation of Novel Bis-Triaziquone Derivatives

    Directory of Open Access Journals (Sweden)

    Yuh-Ling Lin


    Full Text Available Aziridine-containing compounds have been of interest as anticancer agents since late 1970s. The design, synthesis and study of triaziquone (TZQ analogues with the aim of obtaining compounds with enhanced efficacy and reduced toxicity are an ongoing research effort in our group. A series of bis-type TZQ derivatives has been prepared and their cytotoxic activities were investigated. The cytotoxicity of these bis-type TZQ derivatives were tested on three cancer lines, including breast cancer (BC-M1, oral cancer (OEC-M1, larynx epidermal cancer (Hep2 and one normal skin fibroblast (SF. Most of these synthetic derivatives displayed significant cytotoxic activities against human carcinoma cell lines, but weak activities against SF. Among tested analogues the bis-type TZQ derivative 1a showed lethal effects on larynx epidermal carcinoma cells (Hep2, with an LC50 value of 2.02 mM, and also weak cytotoxic activity against SF cells with an LC50 value over 10 mM for 24 hr treatment. Comparing the viability of normal fibroblast cells treated with compound 1a and TZQ, the LC50 value of the latter was 2.52 mM, indicating more toxicity than compound 1a. This significantly decreased cytotoxicity of compound 1a towards normal SF cells, while still maintaining the anticancer activity towards Hep2 cells is an interesting feature. Among the seven compounds synthesized, compound 1c has similar toxicity effects on the three cancer cell lines and SF normal cells as the TZQ monomer.

  12. Selectively N-protected enantiopure 2,5-disubstituted piperazines: avoiding the pitfalls in solid-phase Fukuyama-Mitsunobu cyclizations. (United States)

    Ottesen, Lars K; Olsen, Christian A; Witt, Matthias; Jaroszewski, Jerzy W; Franzyk, Henrik


    An efficient solid-phase route to ring-substituted piperazines from O-linked resin-bound (S)-aziridine-2-methanol is described. Regioselective microwave-assisted aminolysis followed by intramolecular Fukuyama-Mitsunobu cyclization constitute the key features of the protocol. Simple piperazines and diazepanes were readily obtained without preceding N-protection of the acyclic intermediate, whereas attempts to extend this protocol to chiral 2,5-disubstituted piperazines failed. Modifications encompassing N-carbamoylation prior to ring-closure were therefore investigated. However, standard carbamoylating agents, for example, Fmoc-Cl and Alloc-Cl tended to give bis-protected by-products. Thus, novel microwave-assisted solid-phase N-protection procedures were developed for efficient introduction of Fmoc, Boc and Alloc groups. The subsequent cyclization proceeded in moderate to excellent yields depending on the bulk of the side chain and type of N-protecting group. This protocol readily provided novel cis- and trans-2,5-disubstituted piperazines displaying a variety of N-protecting group patterns after further on-resin manipulations. Also, unexpected by-products obtained during these optimization studies were identified and characterized. This includes nosylated ureas arising from an alternative cyclization pathway. Finally, post-cleavage oxidation gave access to the Fmoc/Boc-protected alpha-amino acid as well as the corresponding aldehyde. The chiral piperazines described in this work will enable construction of combinatorial libraries with a higher chemical diversity compared to those containing simple N,N'-difunctionalized piperazines, often present in drug-like compounds.

  13. (1) H NMR Spectra. Part 28: Proton chemical shifts and couplings in three-membered rings. A ring current model for cyclopropane and a novel dihedral angle dependence for (3) J(HH) couplings involving the epoxy proton. (United States)

    Abraham, Raymond J; Leonard, Paul; Tormena, Cláudio F


    The (1) H chemical shifts of selected three-membered ring compounds in CDCl(3) solvent were obtained. This allowed the determination of the substituent chemical shifts of the substituents in the three-membered rings and the long-range effect of these rings on the distant protons. The substituent chemical shifts of common substituents in the cyclopropane ring differ considerably from the same substituents in acyclic fragments and in cyclohexane and were modelled in terms of a three-bond (γ)-effect. For long-range protons (more than three bonds removed), the substituent effects of the cyclopropane ring were analysed in terms of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent dipole perpendicular to and at the centre of the cyclopropane ring and (b) by three identical equivalent dipoles perpendicular to the ring placed at each carbon atom. Model (b) gave a more accurate description of the (1) H chemical shifts and was the selected model. After parameterization, the overall root mean square error for the dataset of 289 entries was 0.068 ppm. The anisotropic effects are significant for the cyclopropane protons (ca 1 ppm) but decrease rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine do not possess a ring current. (3) J(HH) couplings of the epoxy ring proton with side-chain protons were obtained and shown to be dependent on both the H-C-C-H and H-C-C-O orientations. Both density functional theory calculations and a simple Karplus-type equation gave general agreement with the observed couplings (root mean square error 0.5 Hz over a 10-Hz range).

  14. Research of waterborne polyurethane modified with silane coupling agent γ-methacryloxypropyl trimethoxy silane%γ-(甲基丙烯酰氧基)丙基三甲氧基硅烷改性聚氨酯的研究

    Institute of Scientific and Technical Information of China (English)

    王小荣; 沈一丁; 赖小娟


    Silane modified waterborne polyurethane was synthesized by isophorone diisocyanate(IPDI),polytetrahydrofuran glycol(PTMG),γ-methacryloxypropyl trimethoxy silane and aziridine was also used to improve the quality of the film.The structure was characterized by ATR-FT-IR.The effect of MEMO content on emulsion size,the film property of water resistence,mechanical properties,thermal stability,crystallinity and contact angle were studied.The results showed that when m(MEMO)=5.67%,m(AZ)=2%,water resistence rate was low to 14.84%,the maximum tensile strength was 17.334MPa,the breaking elongation was 232.56%,the surface engery and the crystallinity of the polyurethane film was decreased while the thermal stability was enhanced.%以异佛尔酮二异氰酸酯(IPDI)、聚四氢呋喃二醇(PTMG)、γ-(甲基丙烯酰氧基)丙基三甲氧基硅烷(MEMO)为基本原料,制备了硅烷改性聚氨酯乳液,并外加氮丙啶进一步提高了胶膜的性能。衰减全反射傅里叶变换红外光谱(ATR-FT-IR)对产物的结构进行了表征,考察了MEMO含量对乳液粒径、胶膜耐水性、力学性能及热性能的影响,同时对胶膜的结晶性及接触角进行了测试。结果表明ATR-FT-IR证实了MEMO成功地反应到了聚氨酯分子链上;在m(MEMO)=5.67%,m(AZ)=2%时,胶膜的耐水性最低为14.84%,胶膜的最大拉伸强度为17.334MPa,断裂伸长率为232.56%,改性后聚氨酯的热稳定性提高,结晶性及表面能均降低。

  15. Characterization of Iron-Imido Species Relevant for N-Group Transfer Chemistry. (United States)

    Iovan, Diana A; Betley, Theodore A


    A sterically accessible tert-butyl-substituted dipyrrinato di-iron(II) complex [((tBu)L)FeCl]2 possessing two bridging chloride atoms was synthesized from the previously reported solvento adduct. Upon treatment with aryl azides, the formation of high-spin Fe(III) species was confirmed by (57)Fe Mössbauer spectroscopy. Crystallographic characterization revealed two possible oxidation products: (1) a terminal iron iminyl from aryl azides bearing ortho isopropyl substituents, ((tBu)L)FeCl((•)NC6H3-2,6-(i)Pr2); or (2) a bridging di-iron imido arising from reaction with 3,5-bis(trifluoromethyl)aryl azide, [((tBu)L)FeCl]2(μ-NC6H3-3,5-(CF3)2). Similar to the previously reported ((Ar)L)FeCl((•)NC6H4-4-(t)Bu), the monomeric iron imido is best described as a high-spin Fe(III) antiferromagnetically coupled to an iminyl radical, affording an S = 2 spin state as confirmed by SQUID magnetometry. The di-iron imido possesses an S = 0 ground state, arising from two high-spin Fe(III) centers weakly antiferromagnetically coupled through the bridging imido ligand. The terminal iron iminyl complex undergoes facile decomposition via intra- or intermolecular hydrogen-atom abstraction (HAA) from an imido aryl ortho isopropyl group, or from 1,4-cyclohexadiene, respectively. The bridging di-iron imido is a competent N-group transfer reagent to cyclic internal olefins as well as styrene. Although solid-state magnetometry indicates an antiferromagnetic interaction between the two iron centers (J = -108.7 cm(-1)) in [((tBu)L)FeCl]2(μ-NC6H3-3,5-(CF3)2), we demonstrate that in solution the bridging imido can facilitate HAA as well as dissociate into a terminal iminyl species, which then can promote HAA. In situ monitoring reveals the di-iron bridging imido is a catalytically competent intermediate, one of several iron complexes observed in the amination of C-H bond substrates or styrene aziridination.

  16. Cytotoxicity and Radiosensitising Activity of Synthesized Dinitrophenyl Derivatives of 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Khosrou Abdi


    Full Text Available Background and the purpose of the study: Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In thepresent investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide,and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions wasinvestigated.Methods: 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substitutedbenzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking,group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively.Results and major conclusion: Findings of the present study showed that

  17. Very fast (and safe) inactivation of foot-and-mouth disease virus and enteroviruses by a combination of binary ethyleneimine and formaldehyde. (United States)

    Barteling, S J; Cassim, N I


    For FMD vaccine production, inactivation of the FMD virus is the most critical step. Formerly, from 1940 onwards, the virus was inactivated with formaldehyde. This inactivation was relatively slow, about 0.2 - 0.3 log 10 per hour. Because formaldehyde not only reacts with the virus produced but with many other components in the medium, such as proteins and amino acids, its concentration can become rate-limiting and inactivation plots may show tailing-off, resulting in residual infectivity. Many of the bad stories of post-vaccination outbreaks date back to the use of formaldehyde-inactivated vaccines (e.g. the outbreaks in France in 1981 and in Eastern Germany causing the Danish outbreak in 1982). Much faster and safer inactivation was obtained with aziridines and in the 1980s binary ethyleneimine (BEI) was introduced in practically all vaccine production laboratories. If inactivation plots are made of every production batch, as is now required by the European Pharmacopoeia, and these plots show proper inactivation rates, vaccines can considered to be completely safe. Under optimal conditions, inactivation rates are in the range of 0.5 - 1.0 log 10 per hour. In general, the inactivation takes 40-48 hours,which will guarantee complete inactivation of all virus particles in a batch. Since formaldehyde (FA), the 'classical' inactivating agent, inactivates at a rate of 0.3 logs per hour only, a significant contribution of FA to the inactivation of BEI can hardly be expected. However, here it is shown that FA added during the BEI-inactivation process strongly augments inactivation rates with a hundred to thousand-times (to 2.5-3.5 logs per hour). This will enable inactivation during a working day or just overnight with even higher safety levels of the vaccines. Also, it is known that formaldehyde cross-links viral proteins which will stabilise the antigen. The short inactivation times will limit proteolytic destruction of 146 S antigen and increase antigen yields. It is

  18. Regioselective Nucleophilic Ring Opening Reactions of Unsymmetric Thiiranes%非对称环硫乙烷的区域选择性亲核开环反应

    Institute of Scientific and Technical Information of China (English)

    周婵; 许家喜


    Thiiranes are a class of important intermediates in organic synthesis, as well in pharmaceutical and agrochemieal industries as their oxygen analogs oxiranes and nitrogen analogs aziridines. They have been widely applied in the preparation of sulfur-containing compounds, such as diverse thiols and thioethers and so on, via ring opening reaction and isomerization. Nucleophilic ring opening reactions of unsymmetric thiiranes and their regioseleetivity with various widely used nueleophiles are reviewed. Generally, nucleophilic ring opening reactions of unsymmetrie thiiranes occur on their less substituted carbon atom, controlled by the steric hindrance. 2- Alkenyhhiiranes can undergo an SN2' ring opening reaction in some cases via the attack on the β-carbon atom of their alkenyl group. Strong nucleophiles easily lead to desulfurization of thiiranes to afford the corresponding olefins, while the relatively weak nueleophiles readily result in polymerization of thiiranes, affording polythioethers. In the presence of Lewis acid, the electronic effect affects the regioselectivity in ring opening reactions, even as the prominent effect in the reactions. Although aliphatic thiiranes are still attacked predominantly on their less substituted carbon atom with nucleophiles (the steric hindrance control) , aromatic thiiranes and 2-alkenylthiiranes are attacked on their more substituted carbon atom with nucleophiles (the electronic effect control). The current review provides a general rule for the regioselectivity of the nucleophilic ring opening reaction of unsymmetric thiiranes.%环硫乙烷与它的氧类似物环氧乙烷和氮类似物氮杂环丙烷一样,是一类重要的有机合成中间体,在医药和农用化学品工业领域也得到广泛应用。通过开环和异构化反应,还广泛用于制备硫醇和硫醚等含硫化合物。本文总结了常用亲核试剂对非对称环硫乙烷的亲核开环反应及其区域选择性。环硫乙烷

  19. Theoretical Study on the Tautomerization of Cartap Intermediate and Its Isomer%杀螟丹中间体与异构体互变异构理论研究

    Institute of Scientific and Technical Information of China (English)

    于观平; 马翼; 刘鹏飞; 闫涛; 李正名


    The byproduct l-(dimethylamino)-2,3-dithiocyanatopropane(2) can be recycled and partly converted into its isomer 2-(dimethylamino)-l ,3-dithiocyanatopropane(l) , the key intermediate of Cartap, and finally achieved dynamic equilibrium, which can be used to increase the yield. Effects of temperature, catalyst and solvent on the tautomerization of compound 1 and its isomer 2 were investigated. The rearrangement mechanism was studied by density functional theory(DFT) method at B3LYP/6-31G(aziridine carbon atom via an SN 2 mechanism. The solvent effect ( toluene, chloroform, acetone, methanol, ethanol, acetonitrile and DMSO) on tautomerization was also taken into account via polarizable continuum model ( PCM ). Ionization of a neutral substrate results in charge separation, and solvent polarity has a greater effect at the transition state than that for the reactants. Polar solvents lower the energy of the transition more than the solvents of lower polarity. The results show that the solvent effect plays an important role which was supported by experiment data.%研究了合成杀虫剂杀螟丹的关键中间体2-N,N-二甲胺基-1,3-二硫氰基丙烷(有效体)及其异构体1-N,N-二甲胺基-2,3-二硫氰基丙烷(无效体)互变异构反应中溶剂和温度的影响.采用密度泛函理论B3 LYP/6-31 G(d)方法研究了其在气相中的反应机理,确定了相应的过渡态和反应活化能.量子化学计算结果表明,反应首先通过分子内亲核取代环化生成吖丙啶鎓盐活性中间体,硫氰基进攻N-三元环中间体过程中发生了分子内重排转位,转化为异构体.采用极化连续(Polarizable continuum model,PCM)模型研究了反应体系在甲苯、氯仿、丙酮、乙醇、甲醇、乙腈和DMSO溶液中的溶剂效应.结果表明,该重排反应溶剂化效应非常明