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Sample records for aziridines

  1. Asymmetric Synthesis via Chiral Aziridines

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Harden, Adrian; Wyatt, Paul; Andersson, Pher G.; Johansson, Fredrik

    1996-01-01

    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...

  2. Coupling of Vinyl Aziridines and Isocyanates

    OpenAIRE

    Zhang, Kainan; Chopade, Pramod R.; Louie, Janis

    2008-01-01

    Thermal coupling of vinyl aziridines and phenyl isocyanate was evaluated. Although oxazolidinone products were predominant, some reactions afforded a seven-membered ring heterocycle. When Ni/IMes was employed as a catalyst, a wider array of vinyl aziridines underwent coupling reactions. The Ni catalyzed reactions generally afforded vinyl imidazolidinones as major products.

  3. Asymmetric catalytic aziridination of cyclic enones.

    Science.gov (United States)

    De Vincentiis, Francesco; Bencivenni, Giorgio; Pesciaioli, Fabio; Mazzanti, Andrea; Bartoli, Giuseppe; Galzerano, Patrizia; Melchiorre, Paolo

    2010-07-01

    The first catalytic method for the asymmetric aziridination of cyclic enones is described. The presented organocatalytic strategy is based on the use of an easily available organocatalyst that is able to convert a wide range of cyclic enones into the desired aziridines with very high enantiomeric purity and good chemical yield. Such a method may very well open up new opportunities to stereoselectively prepare complex chiral molecules that possess an indane moiety, a framework that is found in a large number of bioactive and pharmaceutically important molecules. PMID:20512797

  4. Styrene Aziridination by Iron(IV) Nitrides.

    Science.gov (United States)

    Muñoz, Salvador B; Lee, Wei-Tsung; Dickie, Diane A; Scepaniak, Jeremiah J; Subedi, Deepak; Pink, Maren; Johnson, Michael D; Smith, Jeremy M

    2015-09-01

    Thermolysis of the iron(IV) nitride complex [PhB(tBuIm)3Fe≡N] with styrene leads to formation of the high-spin iron(II) aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)]. Similar aziridination occurs with both electron-rich and electron-poor styrenes, while bulky styrenes hinder the reaction. The aziridino complex [PhB(tBuIm)3Fe-N(CH2CHPh)] acts as a nitride synthon, reacting with electron-poor styrenes to generate their corresponding aziridino complexes, that is, aziridine cross-metathesis. Reaction of [PhB(tBuIm)3Fe-N(CH2CHPh)] with Me3SiCl releases the N-functionalized aziridine Me3SiN(CH2CHPh) while simultaneously generating [PhB(tBuIm)3FeCl]. This closes a synthetic cycle for styrene azirdination by a nitride complex. While the less hindered iron(IV) nitride complex [PhB(MesIm)3Fe≡N] reacts with styrenes below room temperature, only bulky styrenes lead to tractable aziridino products. PMID:26179563

  5. 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)

    2015-01-15

    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.

  6. 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)

    2014-03-15

    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.

  7. Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

    KAUST Repository

    Zhang, Yan

    2011-01-01

    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. Pyridinium hydrobromide perbromide: a versatile catalyst for aziridination of olefins using Chloramine-T.

    Science.gov (United States)

    Ali, S I; Nikalje, M D; Sudalai, A

    1999-09-01

    [reaction: see text] Pyridinium hydrobromide perbromide (Py x HBr3) catalyzes effectively the aziridination of electron-deficient as well as electron-rich olefins using Chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide) as a nitrogen source to afford the corresponding aziridines in moderate to good yields. PMID:16118868

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -2-carboxylates with [18F]fluoride. The aziridine was activated for nucleophilic attack by substitution of various groups on the aziridine nitrogen atom. Fluorine-18 radiolabelling was followed by ester hydrolysis and removal of the activation group. Totally regioselective ring opening and subsequent...

  10. β-Elimination of an Aziridine to an Allylic Amine: A Mechanistic Study

    OpenAIRE

    Morgan, Kathleen M.; Brown, Garry; Pichon, Monique A.; Green, Geannette Y.

    2011-01-01

    The base-induced rearrangement of aziridines has been examined using a combination of calculations and experiment. The calculations show that the substituent on nitrogen is a critical feature that greatly affects the favorability of both α-deprotonation, and β-elimination to form an allylic amine. Experiments were carried out to determine whether E2-like rearrangement to the allylic amine with lithium diisopropyl amide (LDA) is possible. N-Tosyl aziridines were found to deprotonate on the tos...

  11. Room Temperature Activation of Aryloxysulfonyl Azides by [Co(II)(TPP)] for Selective Radical Aziridination of Alkenes via Metalloradical Catalysis

    Science.gov (United States)

    Subbarayan, Velusamy; Jin, Li-Mei; Xin, Cui; Zhang, X. Peter

    2015-01-01

    Aryloxysulfonyl azides can be effectively activated by commercially available cobalt(II) complex of meso-tetraphenylporphyrin ([Co(TPP)]) at room temperature under neutral and nonoxidative conditions for selective radical aziridination of alkenes via metalloradical catalysis. The [Co(TPP)]-catalyzed radical aziridination system is suitable for different combinations of olefin substrates and aryloxysulfonyl azides, producing various N-aryloxysulfonyl aziridine derivatives in good to excellent yields. In addition to generating the environmentally benign N2 as the only byproduct, this Co(II)-based metalloradical aziridination process features mild reaction conditions and operational simplicity. PMID:26139944

  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

    2014-06-01

    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. Efficient aziridine synthesis in metastable crystalline phases by photoinduced denitrogenation of crystalline triazolines.

    Science.gov (United States)

    de Loera, Denisse; Garcia-Garibay, Miguel A

    2012-08-01

    The solid-state photodenitrogenation of crystalline triazolines proceeds with high efficiency to form the corresponding aziridines in high chemical yields upon selection of the proper irradiation wavelength. It was shown that the solid-to-solid reactions occur by formation of the product in metastable crystalline phases. PMID:22794188

  14. Reactions of Nitroso Hetero Diels-Alder Cycloadducts with Azides: Stereoselective Formation of Triazolines and Aziridines

    Science.gov (United States)

    Bodnar, Brian S.

    2011-01-01

    The addition of azides to acylnitroso hetero Diels-Alder cycloadducts derived from cyclopentadiene affords exo triazolines in excellent yield. The reaction is greatly affected by reducing the level of alkene strain, while sterically demanding azides do not hinder the reaction. Conversion of the triazolines to aziridines is also described. PMID:17429998

  15. Reactions of nitroso hetero-Diels-Alder cycloadducts with azides: stereoselective formation of triazolines and aziridines.

    Science.gov (United States)

    Bodnar, Brian S; Miller, Marvin J

    2007-05-11

    The addition of azides to acylnitroso hetero-Diels-Alder cycloadducts derived from cyclopentadiene affords exo-triazolines in excellent yield. The reaction is greatly affected by the level of alkene strain, while sterically demanding azides do not hinder the reaction. Conversion of the triazolines to aziridines is also described. PMID:17429998

  16. Asymmetric nitrogen. Communications 38. Optically active 1-hydroxyl-, 1-alkoxycarbonyloxy-, and 1-tosyloxy-2, 2-bis(trifluoromethyl)-aziridines

    Energy Technology Data Exchange (ETDEWEB)

    Kostyanovskii, R.G.; Chervin, I.I.; Kadorkina, G.K.; Maldonado, I.K.A.; Nasibov, S.S.

    1985-08-20

    The authors accomplish the separation of diastereomers Xa,b and KIa,b obtained from chiral alkoxycarbonyl derivatives of hexafluoracetone oxime by reaction with CH/sub 2/N/sub 2/ through the corresponding triazolines, which were decomposed to the aziridines by photolysis or by the action of Et/sub 2/O.BF/sub 3/ at 20 C. Diasteromeric 1-alkoxycarbonyloxy-2,2-bis(trifluormethyl)ariridines, which were speated by crystallization and chromatography, under the influence of phenylhydrazine acylates give optically active 1-hydroxy-2,2-bis(trifluoromethyl)aziridine, on the basis of which optically active 1-tosyloxy-2,2-bis(trifluoromethyl)aziridine was obtained. The activation parameters of the epimerization of diasteromeric 1-alkoxycarbonyloxy-2,2-bis(trifluoromethyl)aziridine were found.

  17. Evaluation of aziridine bonding agent by means of chemical and instrumental techniques of analysis

    Directory of Open Access Journals (Sweden)

    Darci Cortes Pires

    2009-01-01

    Full Text Available A new method using wet chemistry and instrumental analysis has been developed for evaluating the ring-opening of aziridine tris [1-(2 methyl aziridinyl] phosphide oxide (MAPO of the bonding agent used in composite propellant. A reduction was observed in the intensity absorption bands in 1400 and 1040 cm-1, characteristic of aziridinic ring. It was also observed, in some cases, that when the number of open aziridinyl ring increases, the NH band in the range 3400-3300 cm-1, that appears with ring-opening, is located in the region of lower wave numbers. The study of the synthesis of MAPO derivative indicated side reactions such as homopolymerization of rings and also, with secondary hydroxyl of the 12-hydroxy stearic acid and probable humidity existent in the original sample.

  18. CURING KINETICS AND PROPERTIES OF ACRYLIC RESIN CURED WITH AZIRIDINE CROSSLINKER

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

    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.

  19. Ring-Opening Reactions of Aziridines Fused to a Conformationally Locked Tetrahydropyran Ring

    Czech Academy of Sciences Publication Activity Database

    Karban, Jindřich; Kroutil, J.; Buděšínský, Miloš; Sýkora, Jan; Císařová, I.

    2009-01-01

    Roč. 2009, č. 36 (2009), s. 6399-6406. ISSN 1434-193X R&D Projects: GA AV ČR IAA400720703; GA AV ČR IAA400720706 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z40550506 Keywords : aziridines * carbohydrates * regioselectivity Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.096, year: 2009

  20. Induction of DNA strand breaks by RSU-1069, a nitroimidazole-aziridine radiosensitizer

    International Nuclear Information System (INIS)

    [2-14C]-RSU-1069 [1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol], either as a parent or following radiation reduction, binds to calf thymus DNA in vitro. Radiation-reduced RSU-1069 binds to a greater extent and more rapidly than the parent compound. RSU-1137, a non-aziridino analogue of RSU-1069, binds following radiation reduction. Radiation-reduced misonidazole exhibits binding ratios a thousand-fold less than those of reduced RSU-1069. Both parent and reduced RSU-1069 cause single strand breaks (ssbs) in pSV2 gpt plasmid DNA with the reduced compound causing a greater number of breaks. Parent and reduced RSU-1137 and misonidazole do not cause ssbs. It is inferred that the aziridine moiety present in both parent and reduced RSU-1069 is required for ssb production. RSU-1069 reacts with inorganic phosphate probably via nucleophilic ring-opening of the aziridine fragment. Incubation of plasmid DNA with reduced RSU-1069 in the presence of either phosphate or deoxyribose-5-phosphate at concentrations greater than 0.35 mol dm-3 prevents strand breakage, whereas 1.2 mol dm-3 deoxyribose does not protect against strand breakage formation. It is proposed that the observed binding to DNA occurs via the aziridine and the reduced nitro group of RSU-1069 and that these two have different target sites. Binding to DNA via the reduced nitro group may serve to increase aziridine attack due to localization at or near its target. (author)

  1. Catalytic aziridination of electron-deficient olefins with an N-chloro-N-sodio carbamate and application of this novel method to asymmetric synthesis.

    Science.gov (United States)

    Minakata, Satoshi; Murakami, Yuta; Tsuruoka, Ryoji; Kitanaka, Shinsuke; Komatsu, Mitsuo

    2008-12-21

    A new method for the aziridination of electron-deficient olefins using an N-chloro-N-sodio carbamate is described; the reaction was promoted by phase-transfer catalysis (solid-liquid) and afforded aziridines from alpha,beta-unsaturated ketones, esters, sulfones and amides. PMID:19048156

  2. One-pot multiple reactions: asymmetric synthesis of 2,6-cis-disubstituted piperidine alkaloids from chiral aziridine.

    Science.gov (United States)

    Yadav, Nagendra Nath; Choi, Jihye; Ha, Hyun-Joon

    2016-07-01

    A divergent, new, and highly stereoselective synthesis of cis-2,6-disubstituted piperidine natural products including isosolenopsins, deoxocassine, and spectaline was achieved from chiral aziridine decorated with appropriate alkyl chains for isosolenopsins or alkynyl groups for deoxocassine and spectaline at C2. The characteristic feature of this synthesis is one-pot sequential reactions under atmospheric hydrogen including the reduction of alkyne (for deoxocassine and spectaline), reductive ring-opening of aziridine, debenzylation, and intramolecular reductive amination in high yields. The prerequisite aziridines were elaborated from commercially available (2S)-hydroxymethylaziridine through oxidation, Wittig olefination, and the Grignard reaction for isosolenopsins or substrate-controlled lithium alkynylate addition for deoxocassine and spectaline. PMID:27189444

  3. 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;

    1998-01-01

    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...

  4. Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines

    Directory of Open Access Journals (Sweden)

    Hongnan Sun

    2015-04-01

    Full Text Available The metal-free synthesis of 2-substituted and 2,3-disubstituted morpholines through a one-pot strategy is described. A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with halogenated alcohols to proceed via an SN2-type ring opening followed by cyclization of the resulting haloalkoxy amine.

  5. Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines

    OpenAIRE

    Hongnan Sun; Binbin Huang; Run Lin; Chao Yang; Wujiong Xia

    2015-01-01

    The metal-free synthesis of 2-substituted and 2,3-disubstituted morpholines through a one-pot strategy is described. A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with halogenated alcohols to proceed via an SN2-type ring opening followed by cyclization of the resulting haloalkoxy amine.

  6. Searches for new interstellar molecules, including a tentative detection of aziridine and a possible detection of propenal

    OpenAIRE

    DICKENS, J.E; IRVINE, W.M; Nummelin, A.; MØLLENDAL, H; Saito, S.; Thorwirth, S.; Hjalmarson, Å.; OhiShi, M

    2001-01-01

    Rotational spectroscopy at millimeter wavelengths is a powerful means of investigating the chemistry of dense interstellar clouds. These regions can exhibit an interesting complement of gas phase molecules, including relatively complex organics. Here we report the tentative first astronomical detection of aziridine (ethylenimine), the possible detection of propenal (acrolein), and upper limits on the abundances of cyclopropenone, furan, hydroxyethanal (glycolaldehyde), thiohydroxylamine (NH2S...

  7. Searches for new interstellar molecules, including a tentative detection of aziridine and a possible detection of propenal

    Science.gov (United States)

    Dickens, J. E.; Irvine, W. M.; Nummelin, A.; Mollendal, H.; Saito, S.; Thorwirth, S.; Hjalmarson, A.; Ohishi, M.

    2001-01-01

    Rotational spectroscopy at millimeter wavelengths is a powerful means of investigating the chemistry of dense interstellar clouds. These regions can exhibit an interesting complement of gas phase molecules, including relatively complex organics. Here we report the tentative first astronomical detection of aziridine (ethylenimine), the possible detection of propenal (acrolein), and upper limits on the abundances of cyclopropenone, furan, hydroxyethanal (glycolaldehyde), thiohydroxylamine (NH2SH), and ethenol (vinyl alcohol) in various interstellar clouds.

  8. Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases.

    Science.gov (United States)

    Schad, Caroline; Baum, Ulrike; Frank, Benjamin; Dietzel, Uwe; Mattern, Felix; Gomes, Carlos; Ponte-Sucre, Alicia; Moll, Heidrun; Schurigt, Uta; Schirmeister, Tanja

    2015-01-01

    Leishmaniasis is one of the major neglected tropical diseases of the world. Druggable targets are the parasite cysteine proteases (CPs) of clan CA, family C1 (CAC1). In previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin L (CL) subfamily of the papain clan CAC1. Both displayed antileishmanial activity in vitro while not showing cytotoxicity against host cells. In further investigations, the mode of action was characterized in Leishmania major. It was demonstrated that aziridines 13b and 13e mainly inhibited the parasitic cathepsin B (CB)-like CPC enzyme and, additionally, mammalian CL. Although these compounds induced cell death of Leishmania promastigotes and amastigotes in vitro, the induction of a proleishmanial T helper type 2 (Th2) response caused by host CL inhibition was observed in vivo. Therefore, we describe here the synthesis of a new library of more selective peptidomimetic aziridine-2,3-dicarboxylates discriminating between host and parasite CPs. The new compounds are based on 13b and 13e as lead structures. One of the most promising compounds of this series is compound s9, showing selective inhibition of the parasite CPs LmaCatB (a CB-like enzyme of L. major; also named L. major CPC) and LmCPB2.8 (a CL-like enzyme of Leishmania mexicana) while not affecting mammalian CL and CB. It displayed excellent leishmanicidal activities against L. major promastigotes (50% inhibitory concentration [IC50] = 37.4 μM) and amastigotes (IC50 = 2.3 μM). In summary, we demonstrate a new selective aziridine-2,3-dicarboxylate, compound s9, which might be a good candidate for future in vivo studies. PMID:26596939

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

    Indian Academy of Sciences (India)

    S PREMILA DEVI; TEJESHWORI SALAM; R H DUNCAN LYNGDOH

    2016-05-01

    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.

  10. 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

    2002-11-01

    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.

  11. Stereospecific Synthesis of Substituted Aziridines by a Crystal-to-Crystal Photodenitrogenation of Δ(2)-1,2,3-Triazolines.

    Science.gov (United States)

    Chung, Tim S; Lopez, Steven A; Houk, K N; Garcia-Garibay, Miguel A

    2015-09-18

    Crystalline cis- or trans-Δ(2)-1,2,3-triazolines prepared by highly stereospecific and regioselective hydrogen bonding-catalyzed dipolar cycloaddition of activated cis- or trans-alkenes with aryl azides undergo a highly stereospecific photodenitrogenation to form the corresponding cis- or trans- azidirines in high chemical yields. While examples involving disubstituted and trisubstituted triazolines highlight steric challenges encountered in the dipolar cycloaddition reaction, the stereochemical control exerted by the crystalline lattice is enhanced by bulky substituents in the triazoline precursors to generate aziridines photochemically. PMID:26338467

  12. Origins of selectivity in Brønsted acid-promoted diazoalkane-azomethine reactions (the aza-Darzens aziridine synthesis).

    Science.gov (United States)

    Troyer, Timothy L; Muchalski, Hubert; Hong, Ki Bum; Johnston, Jeffrey N

    2011-04-01

    The mechanism of the Brønsted acid-catalyzed aza-Darzens reaction is explored by charting the stereochemical outcome of the triflic acid-promoted conversion of trans-triazolines to cis-aziridines. These experiments are consistent with the intermediacy of an α-diazonium-β-amino ester intermediate. PMID:21366339

  13. A Rapid and Simple Method for Quantitative Aziridination from Aminobrominated Derivatives of Olefins under Solvent-free and Mild Conditions%A Rapid and Simple Method for Quantitative Aziridination from Aminobrominated Derivatives of Olefins under Solvent-free and Mild Conditions

    Institute of Scientific and Technical Information of China (English)

    Wei, Junfa; Chen, Zhanguo; Gao, Yanni; Zhang, Peng; Wang, Chuanning; Zhao, Pengfei; Wang, Yun; Shi, Xianying

    2012-01-01

    The urea-catalyzed aziridination of 1,2-vicinal haloamines derived from aminohalogenation of olefins has been developed. This rapid and simple method was carried out by simply grinding the solid mixture of the substrate, K2CO3 and catalytic amount of urea at room temperature in air. The reaction provides a protocol for quantitative preparation of aziridines in a large scope of aminohalogenated derivatives of olefins including α,β-unsaturated ketones, α,β-unsaturated esters and simple olefins. The possible mechanism involving an H-bond promoting deprotonation has been suggested for this reaction.

  14. Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl) butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

    International Nuclear Information System (INIS)

    Introduction: The small molecule 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid (NST732) is a member of the ApoSense family of compounds, capable of selective targeting, binding and accumulation within cells undergoing apoptotic cell death. It has application in molecular imaging and blood clotting particularly for monitoring antiapoptotic drug treatments. We are investigating a fluorine-18-radiolabeled analog of this compound for positron emission tomography studies. Methods: We prepared the tosylate precursor methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(tosyloxymethyl)butanoate (4) to synthesize fluorine-18-labeled NST732. Fluorination reaction of the tosylate precursor in 1:1 acetonitrile:dimethylsulfoxide with tetrabutyl ammonium fluoride proceeds through an aziridine intermediate (4A) to afford two regioisomers: 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-fluorobutanoate (5) and methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoate (6). Acid hydrolysis of the fluoromethylbutanoate (6) isomer produced NST732. As the fluorination reaction of the tosylate precursor proceeds through an aziridine intermediate (4A) and the fluorination conceivably could be done directly on the aziridine, we have separately prepared an aziridine precursor (4A). Fluorine-18 labeling of the aziridine precursor (4A) was performed with [18F]tetrabutyl ammonium fluoride to afford the same two regioisomers (5 and 6). The [18F]2-((5-dimethylamino)naphthalene-1-sulfonamido)methyl)-2-fluorobutanoic acid (NST732) was then obtained by the hydrolysis of corresponding [18F]-labeled ester (6) with 6 N hydrochloric acid. Results: Two regioisomers obtained from the fluorination reaction of aziridine were easily separated by high-performance liquid chromatography. The total radiochemical yield was 15%±3% (uncorrected, n=18) from the aziridine precursor in a 70-min synthesis time with a radiochemical purity >99%. Conclusion

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

    Science.gov (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.

  16. Diastereo- and Enantioselective Iridium Catalyzed Coupling of Vinyl Aziridines with Alcohols: Site-Selective Modification of Unprotected Diols and Synthesis of Substituted Piperidines.

    Science.gov (United States)

    Wang, Gang; Franke, Jana; Ngo, Chinh Q; Krische, Michael J

    2015-06-24

    The chiral cyclometalated π-allyliridium ortho-C,O-benzoate complex (R)-Ir-VIb derived from [Ir(cod)Cl]2, allyl acetate, 4-cyano-3-nitro-benzoic acid, and (R)-MeO-BIPHEP catalyzes the coupling of N-(p-nitrophenylsulfonyl) protected vinyl aziridine 3a with primary alcohols 1a-1l to furnish branched products of C-C bond formation 4a-4l with good levels of anti-diastereo- and enantioselectivity. In the presence of 2-propanol, but under otherwise identical conditions, vinyl aziridine 3a and aldehydes 2a-2l engage in reductive coupling to furnish an equivalent set of adducts 4a-4l with roughly equivalent levels of anti-diastereo- and enantioselectivity. Using enantiomeric iridium catalysts, vinyl aziridine 3a reacts with unprotected chiral 1,3-diols 1m-1o in a site-selective manner to deliver the diastereomeric products of C-allylation syn-4m, -4n, -4o and anti-4m, -4n, -4o, respectively, with good isolated yields and excellent levels of catalyst-directed diastereoselectivity. These adducts were directly converted to the diastereomeric 2,4,5-trisubstituted piperidines syn-5m, -5n, -5o and anti-5m, -5n, -5o. PMID:26074091

  17. Interaction of hepatic microsomal epoxide hydrolase derived from a recombinant baculovirus expression system with an azarene oxide and an aziridine substrate analogue.

    Science.gov (United States)

    Lacourciere, G M; Vakharia, V N; Tan, C P; Morris, D I; Edwards, G H; Moos, M; Armstrong, R N

    1993-03-16

    A recombinant baculovirus (vEHX) encoding rat hepatic microsomal epoxide hydrolase has been constructed. Infection of Spodoptera frugiperda (Sf9) cells with the recombinant virus results in the expression of the enzyme at a level estimated to be between 5% and 10% of the cellular protein. The enzyme, which can be purified in 15% yield by a simple three-step procedure involving detergent extraction, DEAE-cellulose chromatography, and removal of the detergent on hydroxylapatite, has physical and kinetic properties very close to those of the enzyme obtained from rat liver microsomes. The interaction of the enzyme with two nitrogen-containing analogues of the substrate phenanthrene 9,10-oxide (1) was investigated in order to delineate the contributions of the oxirane group and the hydrophobic surface of the substrate to substrate recognition. The enzyme exhibits altered kinetic properties toward 1,10-phenanthroline 5,6-oxide (2) in which the biphenyl group of 1 is replaced with a bipyridyl group, suggesting that hydrophobic interaction between the complementary surfaces of the substrate and active site has an influence on catalysis. The conjugate acid of the aziridine analogue of 1, phenanthrene 9,10-imine (3), in which the oxirane oxygen is replaced with NH, has a pKa of 6.1, which allows the characterization of both the neutral and protonated aziridine (3H+) as substrate analogues for the enzyme. The pH dependence of the solvolysis reveals that 3H+ rearranges to a 65/35 mixture of 9-aminophenanthrene and 9-amino-10-hydroxy-9,10-dihydrophenanthrene 10(3)-fold faster than does 3. The neutral aziridine is a competitive inhibitor (Ki = 26 microM) of the enzyme at pH 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8383521

  18. Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase.

    Science.gov (United States)

    Ling, Y Z; Li, J S; Kato, K; Liu, Y; Wang, X; Klus, G T; Marat, K; Nnane, I P; Brodie, A M

    1998-10-01

    Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole). PMID:9839000

  19. New organocatalyzed transformations of aziridines

    OpenAIRE

    Díaz de los Bernardos Sánchez, Miriam

    2013-01-01

    Entre los intermedios sintéticos más versátiles en química orgánica se encuentran las aziridinas, estos compuestos son heterociclos de tres miembros que presentan una funcionalidad amina. Un gran número de moléculas biológicamente activas contienen en su estructura estos anillos heterocíclicos de tres miembros. En este contexto, la transformación selectiva de aziridinas ha generado un creciente interés en la comunidad sintética hacia la síntesis de diversos aminoácidos, product...

  20. Ring opening of pymisyl-protected aziridines with organocuprates

    DEFF Research Database (Denmark)

    Bornholdt, Jan; Felding, Jakob; Clausen, Rasmus Prætorius; Kristensen, Jesper Langgaard

    2010-01-01

    the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of...

  1. Sulfonyl azide-mediated norbornene aziridination for orthogonal peptide and protein labeling

    Czech Academy of Sciences Publication Activity Database

    Gattner, M. J.; Ehrlich, M.; Vrábel, Milan

    2014-01-01

    Roč. 50, č. 83 (2014), s. 12568-12571. ISSN 1359-7345 Institutional support: RVO:61388963 Keywords : Diels-Adler reactions * transfer RNA synthetase * free click chemistry Subject RIV: CC - Organic Chemistry Impact factor: 6.834, year: 2014

  2. Regioselective Nucleophilic Ring Opening of Epoxides and Aziridines derived from Homoallylic Alcohols

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Groth, Thomas

    1997-01-01

    The regioselectivity of nucleophilic ring opening of some 3,4-epoxy and 3,4-aziridino alcohols has been studied. The nucleophiles chosen were complex hydrides (LiAlH4, Red-Al and DIBAL) and Lipshutz- or Gilman-type organocuprate reagents. The C-4 substituent in the substrates was varied in order ...

  3. Functionalization of olefins by alkoximidoylnitrenes

    Energy Technology Data Exchange (ETDEWEB)

    Subbaraj, A.; Rao, O.S.; Lwowski, W. (New Mexico State Univ., Las Cruces (USA))

    1989-08-04

    (N-Cyano- and N-(methylsulfonyl)alkoxycarbimidoyl)nitrenes, generated in situ from the corresponding azides by 300-nm UV light, convert a variety of olefins cleanly and stereospecifically to the corresponding aziridines. These can readily be hydrolyzed to N-unsubstituted aziridines or ring-opened to allylic isoureas. The nitrenes can also be generated by thermolysis at 80{degree}C. The azides add to norbornene to give triazolines, which lose nitrogen to give the exo-aziridines.

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

    DEFF Research Database (Denmark)

    Olsen, Christian A; Christensen, Caspar; Nielsen, Birgitte; Farah, Mohamed M; Mohamed, Farah M; Witt, Matthias; Clausen, Rasmus P; Kristensen, Jesper L; Franzyk, Henrik; Jaroszewski, Jerzy W

    2006-01-01

    [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, sprin......-loaded N-nitrobenzenesulfonyl-activated aziridine-2-carboxylic acids has been optimized and employed in the synthesis of a number of open-chain and heterocyclic scaffolds, including enantiopure products....

  5. 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

    2015-01-01

    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.

  6. Synthetic Study of Pactamycin: Enantioselective Construction of the Pactamycin Core with Five Contiguous Stereocenters.

    Science.gov (United States)

    Yamaguchi, Mami; Hayashi, Minami; Hamada, Yasumasa; Nemoto, Tetsuhiro

    2016-05-20

    A synthetic study of pactamycin is described. Enantioselective construction of the aminocyclopentitol core of pactamycin bearing five contiguous stereocenters was achieved based on an organocatalytic asymmetric aziridination of 2-cyclopentene-1-one, a regio- and diastereoselective 1,3-dipolar cycloaddition, and a rhodium-catalyzed C-H amination reaction. PMID:27171747

  7. Total Synthesis of balanol, Part 2

    DEFF Research Database (Denmark)

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

    1997-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Mohamed Z. Sliman

    2014-07-01

    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.

  9. Synthesis of enantiopure 3-substituted morpholines

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  10. Synthesis of an Epoxide Carbonylation Catalyst: Exploration of Contemporary Chemistry for Advanced Undergraduates

    Science.gov (United States)

    Getzler, Yutan D. Y. L.; Schmidt, Joseph A. R.; Coates, Geoffrey W.

    2005-01-01

    A class of highly active, well-defined compounds for the catalytic carbonylation of epoxides and aziridines to beta-lactones and beta-lactams are introduced. The synthesis of one of the catalysts involves a simple imine condensation to form the ligand followed by air-sensitive metalation and salt metathesis steps.

  11. Copper-catalyzed cross-coupling reactions of epoxides with gem-diborylmethane: access to γ-hydroxyl boronic esters.

    Science.gov (United States)

    Ebrahim-Alkhalil, Ahmed; Zhang, Zhen-Qi; Gong, Tian-Jun; Su, Wei; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

    2016-04-01

    Herein, we describe a novel copper-catalyzed epoxide opening reaction with gem-diborylmethane. Aliphatic, aromatic epoxides as well as aziridines are converted to the corresponding γ-pinacolboronate alcohols or amines in moderate to excellent yields. This new reaction provides beneficial applications for classic epoxide substrates as well as interesting gem-diborylalkane reagents. PMID:26973991

  12. 四正丁基溴化铵催化的氮杂环丙烷与水合羧酸铜的开环反应%Efficient ring-opening reactions of N-tosylaziridines with hydrous cupric carboxylate mediated by tetra-n-butyl ammonium bromide

    Institute of Scientific and Technical Information of China (English)

    张万轩; 周洁; 黄巍; 苏莉; 汤从国

    2012-01-01

    β-amino alcohol esters could be obtained from the reactions of aziridines with hydrated cupric acetate which were catalysed by tetran-butyl ammonium bromide. Firstly, condition was optimized, such as using different hydration carboxylic acid salts, solvents, reaction temperatures, catalyst of quaternary ammonium salts and the ratios of reaction raw materials to the reaction. 1, 4-dioxane was the best solvent and the preferential molar ratio of aziridine, hydrated cupric acetate and tetrabutyl ammonium bromide was 1 : 0. 6:0. 2. Finally, we expanded the substrate of aziridine and hydrated cupric carboxylates for an excellent yields ( 85%—99%) in a short time. The regioselectivities were 83%—95% for the major products. In the case of cycloalkyl aziridines, the stereochemistry of the ring product was found to be trans-form. Alkyl N-tosyl aziridines and aryl N-tosyl aziridines both mainly underwent cleavage at the terminal carbon atom. A new convenient method for the preparation of β-amino alcohol esters was developed and the role of cation Cu2+ was discussed.%氮杂环丙烷与水合羧酸铜在溴化四丁基铵的催化下可以合成β-胺基醇酯,首先通过条件优化,分别对不同水合羧酸盐、溶剂、反应温度、季铵盐催化剂、反应物料配比对该反应的影响进行研究,得到最优条件:溶剂为1,4-二氧六环,反应条件为回流,氮杂环丙烷、一水乙酸铜、四正丁基溴化铵的摩尔比为1∶0.6∶0.2.然后在此条件下拓展不同反应底物,反应时间短,产物的产率高(85%~99%),产物的区域选择性也高(83%~95%).这种方法对于N-Ts活化的环状氮杂环丙烷,开环产物的立体结构为反式;对芳基和烷基取代的N-Ts活化的氮杂环丙烷,主要开环产物为端位开环产物.对反应条件和Cu2+的作用进行了讨论.

  13. Development of new mitomycin C and porfiromycin analogues.

    Science.gov (United States)

    Iyengar, B S; Lin, H J; Cheng, L; Remers, W A; Bradner, W T

    1981-08-01

    New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data. PMID:7328599

  14. 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

    2013-11-01

    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.

  15. 40 CFR Table 6 to Subpart Jj of... - VHAP of Potential Concern

    Science.gov (United States)

    2010-07-01

    ... aminoazobenzene 1.0 56553 Benzo (a) anthracene 0.01 205992 Benzo (b) fluoranthene 0.01 79469 2-Nitropropane 1.0...′-Methylenedianiline 1.0 90040 o-Anisidine 1.0 1746016 2,3,7,8-Tetrachlorodibenzo-p-dioxin 0.00000006 92875 Benzidine 0... carbamoyl chloride 0.002 75558 1,2-Propylenimine (2-Methyl aziridine) 0.0003 57147 1,1-Dimethyl hydrazine...

  16. 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

    2011-11-01

    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).

  17. 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

    2003-01-01

    @@ 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.

  18. Vicinal Diamination of Alkenes under Rh-Catalysis

    OpenAIRE

    Olson, David E.; Su, Justin Y.; Roberts, D. Allen; Du Bois, J.

    2014-01-01

    The synthesis of 1,2-diamines has been achieved through a single-step, tandem sequence involving Rh-catalyzed aziridination followed by NaI-promoted rearrangement to an isomeric cyclic sulfamide. Facile ring opening of these products in hot water and pyridine affords differentially protected vicinal diamines. Demonstration of the utility of this method for the syntheses of (±)-enduracididine and (±)-allo-enduracididine is highlighted.

  19. Selectively N-protected enantiopure 2,5-disubstituted piperazines

    DEFF Research Database (Denmark)

    Ottesen, Lars Korsgaard; Olsen, Christian Adam; Witt, Matthias;

    2009-01-01

    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 an...... construction of combinatorial libraries with a higher chemical diversity compared to those containing simple N,N'-difunctionalized piperazines, often present in drug-like compounds....

  20. Iron catalyzed C-H activation and synthesis of novel ligands

    OpenAIRE

    Nakanishi, Masafumi

    2007-01-01

    Iron-catalyzed benzylic oxidations, nitrogen transfer reactions such as iminations of sulfides and sulfoxides, aziridinations of olefins and a-aminations of silyl enol ethers were developed. Also, the synthesis of novel nitrogen containing ligands such as 1,4,7-triazacyclononane (TACN) derivatives and dipyridylamine derivatives was undertaken.Iron-catalyzed benzylic oxidation was successfully performed by using a combination of iron(III) chloride (2 mol%) as a catalyst and tert-butyl hydroper...

  1. 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)

    2015-10-14

    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.

  2. Lewis acid Mediated Aza-Diels-Alder Reactions and Asymmetric Alkylations of 2H-azirines

    OpenAIRE

    Risberg, Erik

    2004-01-01

    This thesis describes the use of 2H-azirines, three-membered unsaturatednitrogen-containing heterocycles, as reactive intermediates ina number of Lewis acid promoted alkylations and Diels-Alderreactions providing synthetically useful aziridines. In order to carry out this investigation a new generalprocedure for the ring closure of vinyl azides, forming theresultant 3-substituted-2H-azirines, was developed applying low boiling solventsin closed reaction vessels at elevated temperatures. The a...

  3. Utilization of N-X bonds in the synthesis of N-heterocycles.

    Science.gov (United States)

    Minakata, Satoshi

    2009-08-18

    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

  4. Synthesis and evaluation of alpha-[[(2-haloethyl)amino]methyl]-2- nitro-1H-imidazole-1-ethanols as prodrugs of alpha-[(1-aziridinyl)methyl]-2- nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogues which are radiosensitizers and bioreductively activated cytotoxins

    International Nuclear Information System (INIS)

    alpha-[(1-Aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanols, of general formula ImCH2CH(OH)CH2NCR1R2CR3R4, where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo. Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2(+)-NH2CR1R2CR3R4X X-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I. These 2-haloethylamines were evaluated as prodrugs of the parent aziridines. The rates of ring closure in aqueous solution at pH approximately 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I approximately Br greater than Cl much greater than F). A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2X X- (X = Cl, Br) with aqueous HCO3- ions gives 3-[2-hyroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone. The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. alpha-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1- ethanol (RB 6145, 10), the prodrug of alpha-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions

  5. Fulleropyrrolidine end-capped molecular wires for molecular electronics--synthesis, spectroscopic, electrochemical, and theoretical characterization

    DEFF Research Database (Denmark)

    Sørensen, Jakob Kryger; Fock, Jeppe; Pedersen, Anders Holmen;

    2011-01-01

    synthetic protocols for derivatives terminated with one or two fullero[c]pyrrolidine "electrode anchoring" groups were developed. An aryl-substituted aziridine could in some cases be employed directly as the azomethine ylide precursor for the Prato reaction without the need of having an electron...... state. However, the fluorescence of C(60) was quenched by charge transfer from the wire to C(60). Quantum chemical calculations predict and explain the collapse of coherent electronic transmission through one of the fulleropyrrolidine-terminated molecular wires....

  6. Synthesis of new pyrazolyl-1,3-diazabicyclo[3.1.0]hexe-3-ene derivatives

    Science.gov (United States)

    Kiyani, Hamzeh; Albooyeh, Fereshteh; Fallahnezhad, Saied

    2015-07-01

    A series of new of photochromic 1,3-diazabicyclo[3.1.0]hex-3-ene derivatives based on the skeleton of five-membered pyrazole moiety have been synthesized and characterized by spectral techniques, as well as their photochromic properties were examined under UV light irradiation in various solutions. All these newly synthesized compounds showed good photochromic properties in the both solution and solid states. The UV-Visible spectral analysis of the corresponding pyrazolyl bicyclic aziridines established structure-photochromic behavior relationships.

  7. 5-Azido-4-dimethylamino-1-methyl-1,2,4-triazolium Hexafluoridophosphate and Derivatives

    Directory of Open Access Journals (Sweden)

    Gerhard Laus

    2016-02-01

    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.

  8. A NOVEL METHOD TO PREPARE CROSSLINKED POLYETHYLENEIMINE HOLLOW NANOSPHERES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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).

  9. Synthetic and Mechanistic Studies of Strained Heterocycle Opening Reactions Mediated by Zirconium(IV) Imido Complexes

    OpenAIRE

    Blum, Suzanne A.; Rivera, Vicki A.; Ruck, Rebecca T.; Michael, Forrest E.; Bergman, Robert G.

    2005-01-01

    The reactions of the bis(cyclopentadienyl)(tert-butylimido)zirconium complex (Cp2Zr=N-t-Bu)(THF) (1) with epoxides, aziridines, and episulfides were investigated. Heterocycles without accessible β-hydrogens undergo insertion/protonation of the C–X bond to produce 1,2-amino alcohols (X = O) and 1,2-diamines (X = NR), whereas heterocycles with accessible β-hydrogens undergo elimination/protonation to produce allylic alcohols (X = O) and allylic sulfides (X = S). Mechanistic investigations suppo...

  10. Reduction of 2-chloro-N-phenylpropanamide and 2-methyl-N-phenylaziridine with lithium aluminium hydride

    DEFF Research Database (Denmark)

    Vilhelmsen, Mie Højer; Østergaard, Lars Frøsig; Nielsen, Mogens Brøndsted; Hammerum, Steen

    2008-01-01

    The reduction of 2-chloro-N-phenylpropanamide with LiAlH4 has been re-examined. In contrast to previous findings, we obtain in almost equal quantities two amines from this reaction, namely N-propylaniline and the rearranged product N-isopropylaniline. 2-Methyl-N-phenylaziridine is an intermediate...... the 2-chloropropanamide, which indicates that Lewis acid catalysis (by aluminium chlorohydrides) facilitates the reduction of the aziridine. In addition, Lewis acid catalysis increases the relative yield of the propylamine product. The reduction of 2-chloro-N-phenylpropanamide furnishes 2-phenylamino...

  11. Highly dispersive ion exchangers in the analytical chemistry of uranium, particularly regarding separation methods

    International Nuclear Information System (INIS)

    The reaction of water-insoluble polyvinyl pyrrolidon with uranium VI was investigated and a determination method for uranium was worked out in which the polyvinyl pyrrolidon was used as specific exchanger. Good separations of uranium from numerous transition metal ions were achieved here. The application of this exchanger for a fast and simple elution and determination method was of particular importance. A possible sorption mechanism was suggested based on the capacity curve of uranium with polyvinyl pyrrolidon and nitrogen and chloride content at maximum load. The sorption occurs by coordination of the carbonyl oxygen of single pyrrolidon rings with the protons of the complex acides and uranium. This assumption is supported by IR investigations. The sorbability of other inorganic acids was also investigated and possible structures were formulated for the sorption mechanism. In addition to this, ion exchangers were prepared based on cellulose by converting cellulose powder with aziridine and tris-1-aziridinyl-phosphine oxide. A polyethylene imine cellulose of high capacity was obtained in the conversion of cellulose powder with aziridine. This exchanger absorbs cobalt III very strongly. The exchanger loaded with cobalt III was used to separate the uranium as cyanato complex. The exchanger obtained in converting chlorated cellulose with tris-1-aziridinyl phosphine oxide also absorbs uranium VI very strongly. Thus a separation method of high specifity and selectivity was developed. (orig.)

  12. Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X-ray, NMR, and molecular mechanics.

    Science.gov (United States)

    Arora, S K; Cox, M B; Arjunan, P

    1990-11-01

    X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five-membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross-linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic. PMID:2231597

  13. Specificity of antisera produced against mitomycin C.

    Science.gov (United States)

    Fujiwara, K; Saikusa, H; Kitagawa, T; Takahashi, S; Konishi, Y

    1983-12-01

    The specificity of antisera produced in rabbits for use in mitomycin C (MMC) enzyme immunoassay has been examined employing competitive experiments using several mitomycin analogs and the chemically or biologically degraded preparations of MMC. These studies demonstrate that the antiserum distinguished alterations in the chemical structure of the molecule, showing decreased immunoreactivity with mitomycin A (7.8%) and B (0.78%). On the other hand, porfiromycin and acetyl MMC (Ac-MMC), which commonly possess the substituted groups (methyl and acetyl groups, respectively) at the aziridine ring, showed enhanced reactivity with the antiserum (about two times and ten times as compared to the parent MMC, respectively), suggesting that the antigen used for antibody production was the MMC acylated at the imino group of the aziridine ring. The values of the chemically or biologically degraded preparations of MMC quantified by this enzyme immunoassay were in good agreement with those of the remaining nonreacted MMC measured spectrophotometrically, thus indicating that the anti-MMC antiserum hardly cross-reacted with these degradation products. PMID:6418380

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

    Directory of Open Access Journals (Sweden)

    Xiao-Qiong Li

    2016-04-01

    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.

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

    KAUST Repository

    Drese, Jeffrey H.

    2012-03-01

    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.

  16. A new class of analogues of the bifunctional radiosensitizer alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069): The cycloalkylaziridines

    International Nuclear Information System (INIS)

    A series of compounds related to alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069, 1) were synthesized and evaluated as selective hypoxic cell cytotoxic agents and as radiosensitizers. The aziridine moiety was replaced with a number of other potential alkylating groups including cycloalkylaziridines and azetidines. The data indicated that modification of the aziridine of 1 resulted in a substantial decrease in the ability of the compounds to selectively kill hypoxic cells. However, these modifications did not affect the compounds' in vitro radiosensitizing activity since many of the derivatives were as potent as 1. All of the compounds that were evaluated in vivo were less toxic than 1, and several members of this series had significant activity. The best compound was trans-alpha-[[(4-bromotetrahydro-2H-pyran-3-yl) amino]methyl]-2-nitro-1H-imidazole-1-ethanol (18), which, due to its activity and log P value, is a candidate for additional in vivo studies

  17. A surprising dipolar cycloaddition provides ready access to aminoglycosides.

    Science.gov (United States)

    Dahl, Russell S; Finney, Nathaniel S

    2004-07-14

    This contribution describes the results of a new research effort in our laboratory aimed at the synthesis of novel aminoglycosides and amino-C-glycosides. Despite the importance of such compounds, and the previous development of some methodological solutions, this remains an important area of research. Notable features of our approach, which is distinct from and complementary to previous efforts, are the following: (1) Reliance on a surprising and unprecedented formation of glycal triazolines via an inverse electron demand dipolar cycloaddition of glucal. We believe this desirable transformation has not previously been discovered because of the unusual selection of substrates and solvent required. (2) Very mild reaction conditions. An initial thermal cycloaddition is carried out in an inert solvent, the triazoline generated is photochemically converted to a reactive aziridine, and the crude aziridine undergoes ring opening at room temperature in the presence of a nucleophile and a mild Lewis acid catalyst. (3) Formation of products lacking an N-acyl group, allowing ready synthesis of novel glucosamine derivatives. PMID:15237974

  18. Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics.

    Science.gov (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

    2016-06-01

    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. PMID:27148623

  19. Synthesis of aminoaldonic acids

    DEFF Research Database (Denmark)

    Jørgensen, Christel Thea

    With the aim of synthesising aminoaldonic acids, two 2-acetamido-2-deoxyaldonolactones with D-galacto (6) and D-arabino (11) configuration were prepared from acetylated sugar formazans in analogy with a known procedure. Empolying the same procedure to acetylated sugar phenylhydrazones gave mixtures...... of 2,5-anhydrides and not the expected 2-acetamido-2-deoxy aldose phenylhydrazones. The acetylated phenylhydrazones were found to eliminate acetic acid when heated in aqueous ethanol and 1-phenylazoalkenes could be isolated by crystallisation. By this method the 17, 20, 23 and 25 were prepared from...... aziridino amides 43 and 51 were reductively cleaved with hydrazine to give 3-amino-2,3-dideoxyhexonhydrazides 83 and 85, which were easily converted into the corresponding lactone 84 and acid 86. The aziridine ring of 43 and 51 was also opened with acetic acid to give the 3-amino-3-deoxyhexonic acids 79 and...

  20. Dds-Based Fast Scan Spectrometer

    Science.gov (United States)

    Alekseev, E. A.; Motiyenko, R. A.; Margulès, L.

    2010-06-01

    The technique of direct digital synthesis (DDS) has two important features which enable its application in microwave spectroscopy: micro-Hz tuning resolution and extremely fast frequency switching with continuous phase. We have applied a direct digital synthesizer in a PLL-spectrometer based on backward-wave oscillator (BWO). As result we have obtained an instrument that can cover a 100 GHz bandwidth in less than one hour with high spectral resolution and high precision of frequency measurement. The application of the spectrometer to sub-millimeter wave survey spectra records of several isotopic species of astrophysical molecules (methanol, formamide, methyl formate, aziridine) will be discussed. The support of Université de Lille 1 and le Programme National de Physique Chimie du Milieu Interstellaire is gratefully acknowledged.

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

    Directory of Open Access Journals (Sweden)

    C. Golz

    2015-05-01

    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.

  2. Solid-phase route to Fmoc-protected cationic amino acid building blocks

    DEFF Research Database (Denmark)

    Clausen, Jacob Dahlqvist; Linderoth, Lars; Nielsen, Hanne Mørck;

    2012-01-01

    Diamino acids are commonly found in bioactive compounds, yet only few are commercially available as building blocks for solid-phase peptide synthesis. In the present work a convenient, inexpensive route to multiple-charged amino acid building blocks with varying degree of hydrophobicity was...... developed. A versatile solid-phase protocol leading to selectively protected amino alcohol intermediates was followed by oxidation to yield the desired di- or polycationic amino acid building blocks in gram-scale amounts. The synthetic sequence comprises loading of (S)-1-(p-nosyl)aziridine-2-methanol onto a...... simple neutral amino acids as well as analogs displaying high bulkiness or polycationic side chains was prepared. Two building blocks were incorporated into peptide sequences using microwave-assisted solid-phase peptide synthesis confirming their general utility....

  3. The derivation of 1a-demethylmitomycin G from mitomycin C.

    Science.gov (United States)

    Kono, M; Kasai, M; Shirahata, K; Morimoto, M

    1990-04-01

    Mitomycin G (2) was derived from porfiromycin (10b) in 3 steps via the methanesulfonate (14b) in an overall yield of 39%. On the basis of the established method for the introduction of an exomethylene group in mitomycins with a 9a-methoxy group, the preparation of biologically more important 1a-demethylmitomycin G (5) from mitomycin C (1) was accomplished by the use of a protective acetyl group on the aziridine in an overall yield of 57%. 1a-Demethylmitomycin K (6) was obtained from 5 in a yield of 42%. In a preliminary evaluation of their antitumor activity, compound 5 showed superior activity against sarcoma 180 (sc-ip) to its 1a-methyl congener, i.e., mitomycin G (2). PMID:2112532

  4. Aspects of the chemical stability of mitomycin and porfiromycin in acidic solution.

    Science.gov (United States)

    Underberg, W J; Lingeman, H

    1983-05-01

    Aspects of the degradations of mitomycin and porfiromycin were studied. The initial degradation processes of the compounds in an acidic medium were investigated. Influences of pH, buffers, and other additives such as halogenides and dioctyl sodium sulfosuccinate [sodium 1,4-bis(2-ethylhexyl)sulfosuccinate] were studied. The hydrogen ion catalyzes the degradation of both the uncharged and the protonated species. Anions also promote the degradation of the compounds in an acidic medium. Rate constants for all of the catalytic reactions could be determined. From the pH profiles, after correction for buffer influences, accurate pKa values for the aziridine nitrogens could be obtained. The protective influence of the dioctyl sulfosuccinate ion could be explained. From the data obtained a plausible mechanism for the initial acidic degradation reactions was developed. PMID:6864504

  5. Passive Membrane Permeability of Macrocycles Can Be Controlled by Exocyclic Amide Bonds.

    Science.gov (United States)

    Hickey, Jennifer L; Zaretsky, Serge; St Denis, Megan A; Kumar Chakka, Sai; Morshed, M Monzur; Scully, Conor C G; Roughton, Andrew L; Yudin, Andrei K

    2016-06-01

    We have developed a strategy for synthesizing passively permeable peptidomimetic macrocycles. The cyclization chemistry centers on using aziridine aldehydes in a multicomponent reaction with peptides and isocyanides. The linker region in the resulting product contains an exocyclic amide positioned α to the peptide backbone, an arrangement that is not found among natural amino acids. This amide provides structural rigidity within the cyclic peptidomimetic and promotes the creation of a stabilizing intramolecular hydrogen bonding network. This exocyclic control element also contributes to the increased membrane permeability exhibited by multicomponent-derived macrocycles with respect to their homodetic counterparts. The exocyclic control element is employed along with a strategic placement of N-methyl and d-amino acids to produce passively permeable peptides, which contain multiple polar residues. This strategy should be applicable in the pursuit of synthesizing therapeutically relevant macrocycles. PMID:27120576

  6. Photoinduced and thermal denitrogenation of bulky triazoline crystals: insights into solid-to-solid transformation.

    Science.gov (United States)

    de Loera, Denisse; Stopin, Antoine; Garcia-Garibay, Miguel A

    2013-05-01

    The photoinduced and thermal denitrogenation of crystalline triazolines with bulky substituents leads to the quantitative formation of aziridines in clean solid-to-solid reactions despite very large structural changes in the transition from reactant to product. Analysis of the reaction progress by powder X-ray diffraction, solid-state (13)C CPMAS NMR, solid-state FTIR spectroscopy, and thermal analysis has revealed that solid-to-solid reactions proceed either through metastable phases susceptible to amorphization or by mechanisms that involve a reconstructive phase transition that culminates in the formation of the stable phase of the product. While the key for a solid-to-solid transformation is that the reaction occurs below the eutectic temperature of the reactant and product two-component system, experimental evidence suggests that those reactions will undergo a reconstructive phase transition when they take place above the glass transition temperature. PMID:23547729

  7. Rational drug design and the discovery of the delta2-1,2,3-triazolines, a unique class of anticonvulsant and antiischemic agents.

    Science.gov (United States)

    Kadaba, Pankaja K

    2003-10-01

    The delta(2)- 1,2,3- triazoline anticonvulsants (TRs) may be considered as representing a unique class of "built-in" heterocyclic prodrugs where the active "structure element" is an integral part of the ring system and can be identified only by a knowledge of their chemical reactivity and metabolism. Investigations on the metabolism and pharmacology of a lead triazoline, ADD17014 suggest that the triazolines function as "prodrugs" and exert their anticonvulsant activity by impairing excitatory amino acid (EAA) L-Glutamate (L-Glu) neurotransmission via a unique "dual-action" mechanism. While an active primary beta-amino alcohol metabolite from the parent prodrug acts as an N-methyl-D-aspartate (NMDA)/MK -801 receptor antagonist, the parent triazoline impairs the presynaptic release of L-Glu. Various pieces of theoretical reasoning and experimental evidence have led to the clucidation of the dual-action mechanism. Based on the unique chemistry of the triazolines, and their metabolic pathways, biotransformation products of TRs were predicted to be the beta-amino alcohols V and VA, the alpha-amino acid VI, the triazole VII, the aziridine VIII and the ketimine IX. In vivo and in vitro pharmacological studies of the TR and potential metabolites, along with a full quantitative urinary metabolic profiling of TR indicated the primary beta-amino alcohol V as the active species. It was the only compound that inhibited the specific binding of [3H]MK-801 to the MK-801 site, 56% at 10 micro M drug concentration, but itself had no anticonvulsant activity, suggesting TR acted as a prodrug. Three metabolites were identified; V was the most predominant (45.7 +/- 7.6) % of administered drug, with lesser amounts of VA, (17.3 +/- 5.1) % and very minor amounts of aziridine VIII (4.0 +/- 0.02)%. Since only VIII can yield VA, its formation indicated that the biotransformation of TR occurred, at least in part, through aziridine. No amino acid metabolite was detected, which implied that no

  8. New impurity profiles of recent Australian imported 'ice': methamphetamine impurity profiling and the identification of (pseudo)ephedrine and Leuckart specific marker compounds.

    Science.gov (United States)

    Qi, Ying; Evans, Ian; McCluskey, Adam

    2007-07-01

    Determination of the synthetic route in methamphetamine profiling relies on the identification of key, route specific marker impurity compounds. Impurity profiling of recent crystalline methamphetamine ('ice'), seized by the Australian Federal Police at the Australian border in 2003-2004, identified route specific marker compounds normally associated with two different synthetic approaches in the same samples. Impurities consistent with the ephedrine route included 1,2-dimethyl-3-phenyl aziridine (I), 1,3-dimethyl-2-phenylnaphthalene (VIII) and 1-benzyl-3-methylnaphthalene (IX), alongside N-formylmethamphetamine (V), N,N-di-(beta-phenylisopropyl)amine (XII) and N,N-di-(beta-phenylisopropyl)methylamine (XIII), N-benzoylamphetamine (XIV) and N,N-di-(beta-phenylisopropyl)formamide (XV) commonly associated with the Leuckart route and/or reductive amination. A non-synthetic process related origin of low-level N-formylmethamphetamine is proposed. PMID:17145150

  9. 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)

    2016-01-15

    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.

  10. Highly Strained Heterocycles Constructed from Boron-Boron Multiple Bonds and Heavy Chalcogens.

    Science.gov (United States)

    Braunschweig, Holger; Constantinidis, Philipp; Dellermann, Theresa; Ewing, William C; Fischer, Ingo; Hess, Merlin; Knight, Fergus R; Rempel, Anna; Schneider, Christoph; Ullrich, Stefan; Vargas, Alfredo; Woollins, J Derek

    2016-04-25

    The reactions of a diborene with elemental selenium or tellurium are shown to afford a diboraselenirane or diboratellurirane, respectively. These reactions are reminiscent of the sequestration of subvalent oxygen and nitrogen in the formation of oxiranes and aziridines; however, such reactivity is not known between alkenes and the heavy chalcogens. Although carbon is too electronegative to affect the reduction of elements with lower relative electronegativity, the highly reducing nature of the B-B double bond enables reactions with Se(0) and Te(0) . The capacity of multiple bonds between boron atoms to donate electron density is highlighted in reactions where diborynes behave as nucleophiles, attacking one of the two Te atoms of diaryltellurides, forming salts consisting of diboratellurenium cations and aryltelluride anions. PMID:27027522

  11. Synthesis, characterization and degradation of some polyamines

    International Nuclear Information System (INIS)

    The present assignment deals with the synthesis, characterization and thermal degradation of poly-tertiary butyl aziridine (PTBA) and its copolymers with PMMA. Macro monomer of MMA and TBA was synthesised, its polymerisation and degradation studies were also conducted. Chapter one describes the major synthetic modes and the degradative processes in polymers and the ways and means to retard the degradation are also discussed. Chapter two includes the details of analytical and thermo analytical techniques used in the present research. Chapter three describes the methods employed for purification of chemicals, experimental details and data for the synthesis of monomers and polymers, characterization methodologies and isolation techniques. Chapter four includes the characterization of poly-tertiary butyl aziridine (PTBA) which was synthesised through cationic ring opening polymerization. Significant feature being the production of oligomers in bulk quantity which were collected as cold ring fraction. The mechanisms were proposed for the degradation products. Bifunctional anionic polymerisation of MMA to the desired molecular weight, end capping it with carbon disulfide, and block copolymer synthesis of PMMA with 'living' PTBA is included in chapter five. Chapter six includes the details of the modification procedure adopted for PMMA to generate desirable 'sites' on the polymer. Living PTBA segment were later grafted onto those sites to yield PMMA-g-PTBA. The TG, TVA and SATVA shows that the copolymer is quite stable and the degradation products are almost evenly distributed in liquid and cold ring fraction with very little condensable volatile fraction. In the final chapter the details of synthesis of a new monomer N-methyl-N-tert.butyl-amino ethyl-methacrylate (MTBAEM) are given. The polymerisation and characterization of the MTBAEM is discussed in details. Thermal analysis through TG, TVA and SATVA was conducted, the major fraction was collected at the cold ring

  12. Encapsulation and Characterization of Proton-Bound Amine Homodimers in a Water Soluble, Self-Assembled Supramolecular Host

    Energy Technology Data Exchange (ETDEWEB)

    Pluth, Michael; Fiedler, Dorothea; Mugridge, Jeffrey; Bergman, Robert; Raymond, Kenneth

    2008-10-01

    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 which 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 formation is observed for N-alkylaziridines (R = methyl, isopropyl, tert-butyl), N-alkylazetidines (R = isopropyl, tertbutyl), and N-methylpyrrolidine. At high concentration, formation of a proton-bound homotrimer is observed in the case of N-methylaziridine. The homodimers stay intact inside the assembly over a large concentration range, thereby suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the proton-bound homodimers and suggest that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.

  13. Prebiologically Important Interstellar Molecules

    Science.gov (United States)

    Kuan, Y.-J.; Huang, H.-C.; Charnley, S. B.; Tseng, W.-L.; Snyder, L. E.; Ehrenfreund, P.; Kisiel, Z.; Thorwirth, S.; Bohn, R. K.; Wilson, T. L.

    2004-06-01

    Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

  14. Key role of the Lewis base position in asymmetric bifunctional catalysis: design and evaluation of a new ligand for chiral polymetallic catalysts.

    Science.gov (United States)

    Fujimori, Ikuo; Mita, Tsuyoshi; Maki, Keisuke; Shiro, Motoo; Sato, Akihiro; Furusho, Sanae; Kanai, Motomu; Shibasaki, Masakatsu

    2006-12-27

    New chiral ligands for asymmetric polymetallic catalysts were designed on the basis of the assumption that the higher-order assembly structure is stabilized by modifying the modular unit. The designed ligands 6 and 7 contained a scaffolding cyclohexane ring with a Lewis base phosphine oxide directly attached to the scaffold. A module in the polymetallic complex contains two metals per ligand, and a stable 6-, 5-, 5-membered fused chelation ring system should be generated. Synthesis of these ligands is simple and high yielding, using a catalytic dynamic kinetic resolution promoted by the Trost catalyst as a key step. Ligand function was assessed in a catalytic asymmetric ring-opening reaction of meso-aziridines with TMSCN, a useful reaction for the synthesis of optically active beta-amino acids. The Gd complex generated from Gd(OiPr)3 and the ligand was a highly active and enantioselective catalyst in this reaction. Enantioselectivity was reversed compared to the previously reported d-glucose-derived catalyst containing the same chirality of the individual module. ESI-MS analysis and X-ray crystallographic studies indicate that the assembly state of the modules in the polymetallic catalysts differs depending on the chiral ligand. The difference in the higher-order structure stems from a subtle change (one carbon) in the position of the Lewis base relative to the Gd metal. The change in the higher-order structure of the polymetallic complex led to a dramatic reversal of the enantioselectivity and increased catalyst activity. PMID:17177358

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

    Science.gov (United States)

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

    2016-07-19

    N'-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 = 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. PMID:27100031

  16. 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

    2008-01-01

    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°.

  17. Proceedings of workshop on 'boron chemistry and boron neutron capture therapy'

    International Nuclear Information System (INIS)

    This volume contains the proceedings of the 4th Workshop on 'the Boron Chemistry and Boron Neutron Capture Therapy' held on February 24 in 1992. First, clinical experiences of BNCT in the Kyoto University Research Reactor in 1992 were briefly reported. Then, the killing effects of boron cluster-containing nucleic acid precursors on tumor cells were shown (Chap. 2). The various trials of the optical resolution of B-p-boronophenylalanine for neutron capture therapy were made (Chap. 3). The borate-dextran gel complexes were investigated by the nuclear magnetic resonance spectroscopy. The stability constants of borate complexes were listed, and are useful in the solution chemistry of boron compounds (Chap. 4). The interactions between boron compounds and biological materials were studied by the paper electrophoresis which had been developed by us (Chap. 5). Molecular design of boron-10 carriers and their organic synthesis were reported (Chap. 6). Carborane-containing aziridine boron carriers which were directed to the DNA alkylation were synthesized and their cancer cell killing efficacies were tested (Chap. 7). The solution chemistry of deuterium oxide which is a good neutron moderator was reported, relating to the BNCT (Chap. 8). (author)

  18. Design, synthesis and biological evaluation of diaziridinyl quinone isoxazole hybrids.

    Science.gov (United States)

    Swapnaja, K Jones M; Yennam, Satyanarayana; Chavali, Murthy; Poornachandra, Y; Kumar, C Ganesh; Muthusamy, Krubakaran; Jayaraman, Venkatesh Babu; Arumugam, Premkumar; Balasubramanian, Sridhar; Sriram, Kiran Kumar

    2016-07-19

    A series of novel diaziridinyl quinone isoxazole hybrids (9a-9j) were synthesized starting from 2, 5-dimethoxy acetophenone 1 via Claisen reaction, cyclisation, alkoxy carbonylation, hydrolysis, oxidation and aziridine insertion. All the compounds were screened for antimicrobial, anti-biofilm and cytotoxic activities. Among the screened compounds, the compound 9h showed good antibacterial and anti-biofilm activities with MIC value of 3.9, 3.9, 3.9 and 7.8 μg/mL, respectively, and IC50 values of 1.9, 2.5, 2.8 and 5.1 μM, respectively, against Staphylococcus aureus MTCC 96, S. aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Klebsiella planticola MTCC 530, and also exhibited potent antifungal activity against Candida albicans MTCC 227, C. albicans MTCC 854 and Candida krusei MTCC 3020 equipotent to standard miconazole (MIC value 7.8 μg/mL). All the synthesized compounds exhibited promising cytotoxicity against A549 and PC3 cell lines (IC50 values between 1 and 4 μM). Compounds 9b and 9j exhibited IC50 value of 0.5 μM which was similar to that of Mitomycin C against PC3 cell line. PMID:27089214

  19. Estrogen receptor and progesterone receptor synthesis and degradation in target cells

    International Nuclear Information System (INIS)

    It was the intent of this study to determine the turnover of the estrogen receptor (ER) and progesterone receptors (PR) in rat uterine and human breast cancer cells, respectively, and to examine the effect of estrogen and progestin on PR levels. The rates of synthesis and degradation of ER were determined in rat uterine cells in vitro and in vivo. The affinity labeling antiestrogen, [3H]tamoxifen aziridine, was used in pulse chase experiments to show that the 65,000 molecular weight ER has a half-life of 3-4h in primary cultures of rat uterine cells in vitro and in the intact rat uterus in vivo. Density shift analyses using dense (15N, 13C, 2H) amino acid incorporation corroborate the rapid turnover of ER in rat uterine cell cultures. The regulation of PR by progestins in T47D human breast cancer cells was examined using density shift-dense amino acid incorporation. When T47D cells, which normally maintain high PR levels, are exposed to progestin (R5020), PR levels decline. Receptor half-life, which is 21h in control cells, is reduced to 6h when cells are exposed to 20 nM [3H]R5020. In addition, PR synthesis rate declines exponentially following R5020 exposure. The reduction in receptor level is thus due to dramatic increases in PR degradation as well as marked decreases in PR synthesis

  20. Direct positive selection for improved nitroreductase variants using SOS triggering of bacteriophage lambda lytic cycle.

    Science.gov (United States)

    Guise, C P; Grove, J I; Hyde, E I; Searle, P F

    2007-04-01

    Expression of prodrug-activating enzymes that convert non-toxic substrates to cytotoxic derivatives is a promising strategy for cancer gene therapy. However, their catalytic activity with unnatural, prodrug substrates is often suboptimal. Efforts to improve these enzymes have been limited by the inability to select directly for increased prodrug activation. We have focussed on developing variants of Escherichia coli (E. coli) nitroreductase (NTR) with improved ability to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), and describe here a novel, direct, positive selection for improved enzymes that exploits the alternative life cycles of bacteriophage lambda. In lambda lysogens of E. coli, the activation of the prodrug CB1954 by NTR triggers the SOS response to DNA damage, switching integrated lambda prophages into lytic cycle. This provides a direct, positive selection for phages encoding improved NTR variants, as, upon limiting exposure of lysogenized E. coli to CB1954, only those encoding the most active enzyme variants are triggered into lytic cycle, allowing their selective recovery. We exemplify the selection by isolating highly improved 'turbo-NTR' variants from a library of 6.8 x 10(5) clones, conferring up to 50-fold greater sensitivity to CB1954 than the wild type. Carcinoma cells infected with adenovirus expressing T41Q/N71S/F124T-NTR were sensitized to CB1954 concentrations 40- to 80-fold lower than required with WT-NTR. PMID:17301844

  1. Metal binding sites of the estradiol receptor from calf uterus and their possible role in the regulation of receptor function

    International Nuclear Information System (INIS)

    The existence of putative metal binding sites on the estradiol receptor (ER) molecule from calf uterus was evaluated by immobilizing various divalent metals to iminodiacetate-Sepharose. ER from both crude and highly purified preparations binds to metal-containing adsorbents complexed with Zn(II), Ni(II), Co(II), and Cu(II), but not to those complexed with Fe(II) and Cd(II). Analysis of affinity-labeled ER by [3H]tamoxifen aziridine after elution from a column of Zn(II)-charged iminodiacetate-Sepharose showed that ER fragments obtained by extensive trypsinization were also bound. Zn(II) and the same other metals able to bind ER, when immobilized on resins, inhibit the binding of estradiol to the receptor at micromolar concentration. This inhibition is noncompetitive and can be reversed by EDTA. The inhibition of the hormone binding was still present after trypsin treatment of the cytosol, and it was abolished by preincubation with the hormone. Micromolar concentrations of these metals were able to block those chemical-physical changes occurring during the process of ER transformation in vitro. The presence of metal binding sites that modulate the ER activity in the hormone binding domain of ER is speculated. Since progesterone receptor showed the same pattern of binding and elution from metal-containing adsorbents, the presence of metal binding regulatory sites could be a property of all steroid receptors

  2. Metal binding sites of the estradiol receptor from calf uterus and their possible role in the regulation of receptor function

    Energy Technology Data Exchange (ETDEWEB)

    Medici, N.; Minucci, S.; Nigro, V.; Abbondanza, C.; Armetta, I.; Molinari, A.M.; Puca, G.A. (Istituto di Patologia Generale ed Oncologia, Naples (Italy))

    1989-01-10

    The existence of putative metal binding sites on the estradiol receptor (ER) molecule from calf uterus was evaluated by immobilizing various divalent metals to iminodiacetate-Sepharose. ER from both crude and highly purified preparations binds to metal-containing adsorbents complexed with Zn(II), Ni(II), Co(II), and Cu(II), but not to those complexed with Fe(II) and Cd(II). Analysis of affinity-labeled ER by ({sup 3}H)tamoxifen aziridine after elution from a column of Zn(II)-charged iminodiacetate-Sepharose showed that ER fragments obtained by extensive trypsinization were also bound. Zn(II) and the same other metals able to bind ER, when immobilized on resins, inhibit the binding of estradiol to the receptor at micromolar concentration. This inhibition is noncompetitive and can be reversed by EDTA. The inhibition of the hormone binding was still present after trypsin treatment of the cytosol, and it was abolished by preincubation with the hormone. Micromolar concentrations of these metals were able to block those chemical-physical changes occurring during the process of ER transformation in vitro. The presence of metal binding sites that modulate the ER activity in the hormone binding domain of ER is speculated. Since progesterone receptor showed the same pattern of binding and elution from metal-containing adsorbents, the presence of metal binding regulatory sites could be a property of all steroid receptors.

  3. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility.

    Science.gov (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

    2015-10-15

    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. PMID:26431849

  4. The p53-dependent apoptotic pathway of breast cancer cells (BC-M1) induced by the bis-type bioreductive compound aziridinylnaphthoquinone

    International Nuclear Information System (INIS)

    Several aziridinylbenzoquinone drugs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill cells preferentially within the hypoxia tumor microenvironment. The bioreductive compound of bis-type naphthoquinone synthesized in our laboratory, 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1, 4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1), had the most potent death effect on the breast cancer cells BC-M1 in our previous screening. In the present study, we determined that the mechanism of the death effect of BC-M1 cells induced by AZ-1 was mediated by the apoptosis pathway. We evaluated the cytotoxicity of AZ-1 and the anti-breast cancer drugs tamoxifen and paclitaxel to BC-M1 cells and MCF-7 cells by the MTT assay and measured the apoptosis phenomena by Hoechst 33258 staining for apoptotic bodies. We also quantified the sub-G1 peak area and the ratio of the CH2/CH3 peak area of the cell membrane in BC-M1 cells by flow cytometry and 1H-NMR spectra, respectively. The apoptosis-related protein expressions, including p53, p21, the RNA-relating protein T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2 (cell cycle regulating kinase) and pro-caspase 3, were detected by western blot, and the caspase-3 enzyme activity was also quantified by an assay kit. AZ-1 induced two of the breast cancer cell lines, with IC50 = 0.51 μM in BC-M1 cells and with IC50= 0.57 μM in MCF-7 cells, and showed less cytotoxicity to normal fibroblast cells (skin fibroblasts) with IC50= 5.6 μM. There was a 10-fold difference between two breast cancer cell lines and normal fibroblasts. Of the two anti-breast cancer drugs, tamoxifen showed IC50= 0.12 μM to BC-M1 cells and paclitaxel had much less sensitivity than AZ-1. The expression of p53 protein increased from 0.5 to 1.0 μM AZ-1 and decreased at 2.0 μM AZ-1. The p21 protein increased from 0.5 μM AZ-1, with the highest at 2 μM AZ

  5. 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

    2009-01-01

    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

  6. Triazolines--XXVII. delta2-1,2,3-triazoline anticonvulsants: novel 'built-in' heterocyclic prodrugs with a unique 'dual-action' mechanism for impairing excitatory amino acid L-glutamate neurotransmission.

    Science.gov (United States)

    Kadaba, P K; Stevenson, P J; P-Nnane, I; Damani, L A

    1996-02-01

    The delta2-1,2,3-triazoline anticonvulsants (1) may be considered as representing a unique class of 'built-in' heterocyclic prodrugs where the active 'structure element' is an integral part of the ring system and can be identified only by a knowledge of their chemical reactivity and metabolism. Investigations on the metabolism and pharmacology of a lead triazoline, ADD17014 (1a), suggest that the triazolines function as 'prodrugs' and exert their anticonvulsant activity by impairing excitatory amino acid (EAA) L-glutamate (L-Glu) neurotransmission via a unique 'dual-action' mechanism. While an active beta-amino alcohol metabolite, 2a, from the parent prodrug acts as an N-methyl-D-aspartate (NMDA)/MK-801 receptor antagonist, the parent triazoline impairs the presynaptic release of L-Glu. Various pieces of theoretical reasoning and experimental evidence led to the elucidation of the dual-action mechanism. Based on the unique chemistry of the triazolines, the potential metabolic pathways and biotransformation products of 1a were predicted to be the beta-amino alcohols 2a and 2a', the alpha-amino acid 3a, the triazole 4a, the aziridine 5a, and the ketimine 6a. In vivo and in vitro pharmacological studies of 1a and potential metabolities, along with a full quantitative urinary metabolic profiling of 1a, indicated the beta-amino alcohol 2a as the active species. It was the only compound that inhibited the specific binding of [3H]MK-801 to the MK-801 site, 56% at 10 microM drug concentration, but itself had no anticonvulsant activity, suggesting 1a acted as a prodrug. Three metabolites were identified; 2a was the most predominant, with lesser amounts of 2a', and very minor amounts of aziridine 5a. Since only 5a can yield 2a', its formation indicated that the biotransformation of 1a occurred, at least in part, through 5a. No amino acid metabolite 3a was detected, which implied that no in vivo oxidation of 2a or oxidative biotransformation of 1a or 5a by hydroxylation at

  7. Inhibition of Grb2-mediated activation of MAPK signal transduction suppresses NOR1/CB1954-induced cytotoxicity in the HepG2 cell line.

    Science.gov (United States)

    Gui, Rong; Li, Dengqing; Qi, Guannan; Suhad, Ali; Nie, Xinmin

    2012-09-01

    The nitroreductase oxidored-nitro domain containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyngeal carcinoma (NPC). We have previously demonstrated that NOR1 overexpression is capable of converting the monofunctional alkylating agent 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) into a toxic form by reducing the 4-nitro group of CB1954. Toxic CB1954 is able to enhance cell killing in the NPC cell line CNE1; however, the underlying mechanisms remain unknown. Using cDNA microarrays and quantitative real-time PCR, we previously discovered that NOR1 increases the expression of growth factor receptor-bound protein 2 (Grb2) mRNA by 4.8-fold in the human hepatocellular carcinoma cell line HepG2. In the present study, we revealed that NOR1 increased Grb2 protein expression by 3-fold in HepG2 cells. Additionally, we demonstrated that NOR1 enhanced CB1954-induced cell killing in HepG2 cells, and cell cytotoxicity was inhibited with the tyrosine kinase inhibitor genistein, or by stable transfection of Grb2 small hairpin RNA (shRNA) pU6(+27)-shGrb2 to silence the expression of Grb2. Western blot analysis revealed that Grb2 downregulation may reduce the activity of the mitogen-activated protein kinase (MAPK). Inhibiting the activation of MAPK using the methyl ethyl ketone (MEK) inhibtor PD98059 suppressed CB1954-induced cell killing. These results suggested that the NOR1 gene enhances CB1954-mediated cell cytotoxicity through the upregulation of Grb2 expression and the activation of MAPK signal transduction in the HepG2 cell line. PMID:23741254

  8. Metabolites and DNA adduct formation from flavoenzyme-activated porfiromycin.

    Science.gov (United States)

    Pan, S S; Iracki, T

    1988-08-01

    Porfiromycin was reductively metabolized by NADPH cytochrome P-450 reductase and xanthine oxidase under anaerobic conditions. The production of metabolites varied with the pH and the contents of the reaction buffer. In Tris buffer, two major metabolites were produced at pH 7.5 and above, whereas one major metabolite was produced at pH 6.5. The three major metabolites were separated and isolated by HPLC. Identification by californium-252 plasma desorption mass spectrometry showed that the two major metabolites from pH 7.5 were (trans) and (cis)-forms of 7-amino-1-hydroxyl-2-methylaminomitosene and the major metabolite from pH 6.5 was 7-amino-2-methylaminomitosene. All three major metabolites showed substitutions at the C-1 position. DNA was alkylated readily by enzyme-activated porfiromycin. Digestion of porfiromycin-alkylated DNA by DNase, snake venom phosphodiesterase, and alkaline phosphatase resulted in an insoluble nuclease-resistant fraction and a soluble fraction. The nuclease-resistant fraction reflected a high content of cross-linked adducts. Upon HPLC analysis, the solubilized fraction contained two monofunctionally linked porfiromycin adducts and a possibly cross-linked dinucleotide. The major adduct was isolated by HPLC and identified by NMR, as N2-(2'-deoxyguanosyl)-7-amino-2-methylaminomitosene. The N2 position of deoxyguanosine appeared as the major monofunctional alkylating site for DNA alkylation by porfiromycin. Thus, mitomycin C and porfiromycin (which differs from mitomycin C only by the addition of a methyl group to the aziridine nitrogen) share the same enzymatic activating mechanism that leads to the formation of the same types of metabolites and the same specificity of DNA alkylation. PMID:3412325

  9. Conversion of pristine and p-doped sulfuric-acid-treated single-walled carbon nanotubes to n-type materials by a facile hydrazine vapor exposure process

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Pen-Cheng, E-mail: wangpc@ess.nthu.edu.tw [Department of Engineering and System Science, National Tsing Hua University, 101 Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Liao, Yu-Chun [Department of Engineering and System Science, National Tsing Hua University, 101 Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076, Taiwan (China); Lai, Yu-Ling; Lin, Ying-Chang [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076, Taiwan (China); Su, Ching-Yuan; Tsai, Chuen-Horng [Department of Engineering and System Science, National Tsing Hua University, 101 Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Hsu, Yao-Jane, E-mail: yjhsu@nsrrc.org.tw [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076, Taiwan (China)

    2012-05-15

    Highlights: Black-Right-Pointing-Pointer Discovery of a facile method to n-dope carbon nanotubes by vapor-phase hydrazine. Black-Right-Pointing-Pointer Confirming covalently bound sulfonic groups on CNTs treated with sulfuric acid. Black-Right-Pointing-Pointer Spectroscopic investigation of CNTs' bonding structures after hydrazine treatment. Black-Right-Pointing-Pointer Proposing a cycloaddition reaction between graphenic domains of CNTs and reactive nitrogen-containing radicals thermally decomposed from hydrazine. Black-Right-Pointing-Pointer Establishing aziridine as a probable n-doping chemical entity on hydrazine-treated CNTs. - Abstract: It was found in this study that a facile vapor-phase hydrazine (N{sub 2}H{sub 4}) treatment could effectively convert pristine and even p-doped sulfuric-acid-treated single-walled cabon nanotubes (SWCNTs) to n-type materials. The Raman spectroscopy results show that the facile vapor-phase hydrazine treatment could suppress the intensity of SWCNTs' radial breathing modes and alter SWCNTs' D-band vs. G-band intensity ratio. The sheet resistance measurement results show that the n-doping effect exerted by the vapor-phase hydrazine treatment could overwhelmingly counteract sulfuric acid's p-doping effect and subdue the SWCNTs' acquired p-type characteristics rendered by the sulfuric acid treatment. The ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy results suggest that certain reactive nitrogen-containing radicals thermally decomposed from hydrazine, such as nitrene and amidogen, could covalently functionalize CNTs and then n-dope the functionalzed CNTs.

  10. Metal binding sites of the estradiol receptor from calf uterus and their possible role in the regulation of receptor function.

    Science.gov (United States)

    Medici, N; Minucci, S; Nigro, V; Abbondanza, C; Armetta, I; Molinari, A M; Puca, G A

    1989-01-10

    The existence of putative metal binding sites on the estradiol receptor (ER) molecule from calf uterus was evaluated by immobilizing various divalent metals to iminodiacetate-Sepharose. ER from both crude and highly purified preparations binds to metal-containing adsorbents complexed with Zn(II), Ni(II), Co(II), and Cu(II), but not to those complexed with Fe(II) and Cd(II). Elution of ER was obtained by chelating agents or by imidazole, thus indicating that histidine residues on the ER molecule are involved in the interaction with the metal. Analysis of affinity-labeled ER by [3H]tamoxifen aziridine after elution from a column of Zn(II)-charged iminodiacetate-Sepharose showed that ER fragments obtained by extensive trypsinization were also bound. Zn(II) and the same other metals able to bind ER, when immobilized on resins, inhibit the binding of estradiol to the receptor at micromolar concentrations. This inhibition is noncompetitive and can be reversed by EDTA. The inhibition of the hormone binding was still present after trypsin treatment of the cytosol, and it was abolished by preincubation with the hormone. Micromolar concentrations of these metals were able to block those chemical-physical changes occurring during the process of ER transformation in vitro. Furthermore, if added to pretransformed ER-hormone complex, they strongly inhibited the binding of the complex to isolated nuclei. The presence of metal binding sites that modulate the ER activity in the hormone binding domain of ER is therefore speculated. Since progesterone receptor showed the same pattern of binding and elution from metal-containing adsorbents, the presence of metal binding regulatory sites could be a property of all steroid receptors. PMID:2706244

  11. Triazolines. XXI: Preformulation degradation kinetics and chemical stability of a novel triazoline anticonvulsant.

    Science.gov (United States)

    Freeke Hamelijnck, M A; Stevenson, P J; Kadaba, P K; Damani, L A

    1992-04-01

    The effect of pH, temperature, and two buffer species (citric acid-phosphate and bicarbonate-carbonate) on the stability of 1-(4-chlorophenyl)-5-(4-pyridyl)-delta 2-1,2,3-triazoline (ADD17014; 1), a novel triazoline anticonvulsant, was determined by HPLC. One of the main degradation products of 1 at pH 7.0 was isolated by TLC and identified as the aziridine derivative by MS. Investigations were carried out over a range of pH (2.2-10.7) and buffer concentration [ionic strength (mu), 0.25-4.18] at 23 degrees C. The degradation followed buffer-catalyzed, pseudo-first-order kinetics and was accelerated by a decrease in pH and an increase in temperature. The activation energy for the degradation in citric acid-phosphate buffer (pH 7.0 and constant ionic strength mu at 0.54) was 12.5 kcal/mol. General acid catalysis was observed at pH 7.0 in citric acid-phosphate buffer. The salt effect on the degradation obeyed the modified Debye-Hückel equation well; however, the observed charge product (ZAZB) value (2.69) deviated highly from the theoretical value (1.0), perhaps because of the high mu values (0.25-4.18) of the solutions used. The stability data will be useful in preformulation studies in the development of a stable, oral dosage form of 1. PMID:1501079

  12. Structures of the anticancer compounds N-(2-hydroxyethyl)-2-(3-nitro-1,2,4-triazol-1-yl)-acetamide (RB-6110) and 5-(1-aziridinyl)-3-nitro-1-(3-oxo-1-butyl)-1,2,4- triazole (RB-6162).

    Science.gov (United States)

    McKenna, R; Jenkins, T C; Neidle, S

    1988-12-01

    RB-6110: C6H9N5O4, Mr = 215.17, monoclinic, C2/c, a = 20.595 (3), b = 4.713 (1), c = 19.914 (4) A, beta = 110.69 (1) degree, V = 1808.3 A3, Z = 8, Dx = 1.588 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 0.838 mm-1, F(000) = 675, T = 298 K, final R = 0.042 for 1219 observed reflections with I greater than or equal to 1.5 sigma (I). RB-6162: C8H11N5O3, Mr = 225.21, monoclinic, P2(1)/c, a = 7.515 (1), b = 14.758 (2), c = 9.813 (1) A, beta = 108.49 (1) degree, V = 1032.1 A3, Z = 4, Dx = 1.450 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 0.927 mm-1, F(000) = 472, T = 298 K, final R = 0.042 for 1113 observed reflections with I greater than or equal to 1.5 sigma (I). RB-6110 and RB-6162 are 3-nitro-1,2,4-triazoles with potential application as anticancer agents. The nitro groups are in the plane of the aromatic triazole ring with dihedral angles of 1.2 (4) and 4.6 (4) degrees, respectively. The arizidine substituent of RB-6162 is almost perpendicular [dihedral angle 80.1 (4) degrees] to the triazole plane. Molecular-orbital calculations on RB-6162 have confirmed that this geometry is energetically favoured. The energy barrier to rotation about the triazole-aziridine bond has been determined as 51.5 (5) kJ mol-1 by the dynamic NMR method. PMID:3271560

  13. Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Khoshayand Mohammad

    2012-07-01

    Full Text Available Abstract 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 the present 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 was investigated. Methods 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, 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-29 cell 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

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

    Directory of Open Access Journals (Sweden)

    Khosrou Abdi

    2012-07-01

    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

  15. Effects of ethanolamine and choline on thiotepa cellular accumulation and cytotoxicity in L1210 cells

    International Nuclear Information System (INIS)

    The amino alcohols, ethanolamine and choline, were studied for their effects on (a) L1210 cell growth, (b) N,N',N double-prime-triethylenetheiphosphoramide (thiotepa)-induced growth inhibition of L1210 cells, and (c) 14C accumulation by L1210 cells incubated with [14C]thiotepa. Ethanolamine, at concentrations up to 300 microM, had no effect on L1210 cell growth but, at concentrations greater than 300 microM, produced a dose-dependent reduction in cell growth. Choline, at concentrations up to 20 mM, had no effect on L1210 cell growth. Neither ethanolamine, at 250 microM, nor choline, at 10 mM, altered the ability of thiotepa to reduce L1210 cell growth. Neither ethanolamine, at 250 microM, nor choline, at 10 mM, affected the rapid phase of 14C accumulation by L1210 cells incubated with [14C]thiotepa. The slow phase of 14C accumulation by L1210 cells incubated with 5 microM [14C]thiotepa, a process which is 80-85% due to production of [14C]phosphatidylethanolamine, was not affected by 250 microM choline. In contrast, ethanolamine produced a dose-dependent reduction in this slow rate of 14C accumulation. The reduction in the slow rate of 14C accumulation produced by ethanolamine was due almost entirely to a decrease in the accumulation of nonexchangeable 14C. Kinetic analysis of the inhibition of 14C accumulation produced by 25, 100, and 250 microM ethanolamine was compatible with competitive inhibition. Thin layer chromatography of cell extracts showed that the ability of ethanolamine to reduce 14C accumulation by L1210 cells incubated with [14C]thiotepa was due solely to reduction in production of [14C]phosphatidylethanolamine. These results are all compatible with and predicted by our previously described scheme wherein thiotepa enters cells by simple diffusion and serves as a prodrug for aziridine

  16. Characterization of Iron-Imido Species Relevant for N-Group Transfer Chemistry

    Science.gov (United States)

    Iovan, Diana A.; Betley, Theodore A.

    2016-01-01

    A sterically accessible tert-butyl-substituted dipyrrinato di-iron(II) complex [(tBuL)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 FeIII species was confirmed by 57Fe Mössbauer spectroscopy. Crystallographic characterization revealed two possible oxidation products: (1) a terminal iron iminyl from aryl azides bearing ortho isopropyl substituents, (tBuL)FeCl(•NC6H3-2,6-iPr2); or (2) a bridging di-iron imido arising from reaction with 3,5-bis(trifluoromethyl)aryl azide, [(tBuL)FeCl]2(μ-NC6H3-3,5-(CF3)2). Similar to the previously reported (ArL)FeCl(•NC6H4-4-tBu), the monomeric iron imido is best described as a high-spin FeIII 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 FeIII 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 [(tBuL)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. PMID:26788747

  17. 7-N-(mercaptoalkyl)mitomycins: implications of cyclization for drug function.

    Science.gov (United States)

    Na, Younghwa; Wang, Shuang; Kohn, Harold

    2002-05-01

    The Kyowa Hakko Kogyo and Bristol-Myers Squibb companies reported that select mitomycin C(7) aminoethylene disulfides displayed improved pharmacological profiles compared with mitomycin C (1). Mechanisms have been advanced for these mitomycins that differ from 1. Central to many of these hypotheses is the intermediate generation of 7-N-(2-mercaptoethyl)mitomycin C (5). Thiol 5 has been neither isolated nor characterized. Two efficient methods were developed for mitomycin (porfiromycin) C(7)-substituted thiols. In the first method, the thiol was produced by a thiol-mediated disulfide exchange process using an activated mixed mitomycin disulfide. In the second route, the thiol was generated by base-mediated cleavage of a porfiromycin C(7)-substituted thiol ester. We selected four thiols, 7-N-(2-mercaptoethyl)mitomycin C (5), 7-N-(2-mercaptoethyl)porfiromycin (12), 7-N-(2-mercapto-2-methylpropyl)mitomycin C (13), and 7-N-(3-mercaptopropyl)porfiromycin (14), for study. Thiols 5 and 12-14 differed in the composition of the alkyl linker that bridged the thiol with the mitomycin (porfiromycin) C(7) amino substituent. Thiol generation was documented by HPLC and spectroscopic studies and by thiol-trapping experiments. The linker affected the structure of the thiol species and the stability of the thiol. We observed that thiols 5 and 12 existed largely as their cyclic isomers. Evidence is presented that cyclization predominantly occurred at the mitomycin C(7) position. Correspondingly, alkyl linker substitution (13) or extension of the linker to three carbons (14) led to enhanced thiol stability and the predominant formation of the free thiol species. The dominant reaction of thiols 5 and 12-14 or their isomers was dimerization, and we found no evidence that thiol formation led to mitosene production and aziridine ring-opening. These findings indicated that thiol generation was not sufficient for mitomycin ring activation. The potential pharmacological advantages of

  18. Characterization of Iron-Imido Species Relevant for N-Group Transfer Chemistry.

    Science.gov (United States)

    Iovan, Diana A; Betley, Theodore A

    2016-02-17

    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. PMID:26788747

  19. Role of estrogen receptor ligand and estrogen response element sequence on interaction with chicken ovalbumin upstream promoter transcription factor (COUP-TF).

    Science.gov (United States)

    Klinge, C M

    1999-11-01

    Estrogen-responsive genes are regulated by altering the balance of estrogen receptor (ER) interaction with transcription activators and inhibitors. Here we examined the role of ER ligand on ER interaction with the Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP-TF) orphan nuclear receptor. COUP-TF binding to half-site estrogen response elements (EREs) was increased by the addition of estradiol (E2) -liganded ER (E2-ER), but not by ER liganded with the antiestrogens 4-hydroxytamoxifen (4-OHT-ER) or tamoxifen aziridine (TAz-ER). ER did not bind to single half-sites. Conversely, COUP-TF enhanced the ERE binding of purified E2-ER, but did not affect TAz-ER-ERE binding. In contrast, only antiestrogens enhanced direct interaction between ER and COUP-TF as assessed by GST pull-down assays. Identical results were obtained using either purified bovine or recombinant human ERalpha. Co-immunoprecipitation assays showed that ER and COUP-TF interact in extracts from MCF-7 and ERalpha-transfected MDA-MB-231 cells. Here we document that ER ligand impacts COUP-TF-ER interaction. COUP-TF interaction is mediated by the DNA binding and ligand-binding domains of ER. We suggest that changes in ER conformation induced by DNA binding reduce ER-COUP-TF interaction. Transient transfection of human MCF-7 breast cancer cells with a COUP-TFI expression vector repressed E2-induced luciferase reporter gene expression from single or multiple tandem copies of a consensus ERE. COUP-TFI stimulated 4-OHT-induced luciferase activity from a minimal ERE. Alone, COUP-TFI increased transcription from ERE half-sites or a single ERE in a sequence-dependent manner. These data provide evidence that the ERE sequence and its immediate flanking regions influence whether COUP-TF enhances, inhibits, or has no effect on ER ligand-induced ERE reporter gene expression and that COUP-TFI activates gene transcription from ERE half-sites. We suggest that COUP-TFI plays a role in mitigating estrogen

  20. Characterization of Porphyrin-Co(III)-'Nitrene Radical' Species Relevant in Catalytic Nitrene Transfer Reactions.

    Science.gov (United States)

    Goswami, Monalisa; Lyaskovskyy, Volodymyr; Domingos, Sérgio R; Buma, Wybren Jan; Woutersen, Sander; Troeppner, Oliver; Ivanović-Burmazović, Ivana; Lu, Hongjian; Cui, Xin; Zhang, X Peter; Reijerse, Edward J; DeBeer, Serena; van Schooneveld, Matti M; Pfaff, Florian Felix; Ray, Kallol; de Bruin, Bas

    2015-04-29

    mono-nitrene case remains elusive, but some plausible candidates are NH3, NH2(-), NsNH(-), and OH(-); NsNH(-) being the most plausible. Conversion of mono-nitrene species 3(P1)(Ns) into bis-nitrene species 5(P1)(Ns) upon reaction with 4(Ns) was demonstrated. Solutions containing 3(P1)(Ns) and 5(P1)(Ns) proved to be still active in catalytic aziridination of styrene, consistent with their proposed key involvement in nitrene transfer reactions mediated by cobalt(II) porphyrins. PMID:25844713

  1. 一个与化学因素致鼻咽癌相关的硝基还原酶基因的克隆与鉴定%Molecular Cloning and Characterization of a Novel Nitroreductase Gene, NOR1, Possibly Involved in Chemical Carcinogenesis of NPC

    Institute of Scientific and Technical Information of China (English)

    聂新民; 周鸣; 唐珂; 张必成; 向娟娟; 熊炜; 吕红斌; 李小玲; 李桂源

    2003-01-01

    在运用cDNA microarray分析鼻咽癌细胞系CNE1与正常鼻咽上皮细胞差异表达基因的基础上,发现ESTW95442在细胞系CNE1中存在明显表达下调.随后采用生物信息学的方法克隆出了该EST所代表的硝基还原酶基因NOR1(GenBank登录号为AF462348).Northern印迹分析表明,该基因在脑、心脏、肺等正常组织中均有2个转录产物(1.6 kb,1.2 kb).RT-PCR分析显示,NOR1基因在鼻咽癌活检组织中也存在表达下调.但酶活性测定实验表明,它在鼻咽癌细胞系CNE1中的活性比正常鼻咽上皮细胞高.通过基因转染实验发现NOR1 基因具有与细菌硝基还原酶NTR相似的功能,能够将单功能烷基化试剂2-硝基苯氮丙啶类化合物CB1954的第4位硝基还原成亚硝基从而生成细胞毒性物质.研究结果表明,NOR1基因可能通过它的亚硝化作用及高活性而参与化学性因素致鼻咽癌的过程.%The expression of ESTW95442 is down regulated in nasopharyngeal carcinoma cell line CNE1, in comparison with normal nasopharyngeal epithelial cell, which was confirmed by cDNA microarray analysis. Subsequently, the novel gene,NOR1 (GenBank Accession No.AF462348), corresponding to ESTW95442 was cloned by cDN A cloning and bioinformatics analysis. Northern blot analysis showed that NOR1 gene had two transcripts (1.6 kb, 1.2 kb) and expressed in almost normal human tissues. RT PCR analysis showed that the expression of NOR1 was also d own regulated in nasopharyngeal carcinoma (NPC) biopsies. However, NOR1 had high enzyme activity in CNE1 compared with normal nasopharyngeal epithelial c ell. The conditioned media of CNE1 cells transfected with full lengthNOR1 cDNA showed that the NOR1 had the similar activity to the bacterial nitroreductase NTR, which could convert monofunction alalkylating agent, CB1954([5 aziridin 1 yl]2,4 dinitrobenzamide) into a toxic form by redu cing the 4 nitro group of CB1954. The findings suggest that the NOR1

  2. 含氟丙烯酸酯乳液整理剂的合成及其在织物防水防油整理中的应用%Synthesis of fluoridated acrylic emulsion finishing agent and application in water and oil proofing finish on cotton fabric

    Institute of Scientific and Technical Information of China (English)

    何彦萱; 刘金华; 郭玉良; 刘军; 卢霜

    2014-01-01

    以甲基丙烯酸甲酯、丙烯酸异冰片酯、甲基丙烯酸十二烷基酯、六氟丙烯酸丁酯、二甲基丙烯酸丁二醇酯、3-氯-2-羟丙基甲基丙烯酸酯为单体,偶氮二异丁基脒盐酸盐为引发剂,合成阳离子含氟丙烯酸酯乳液,并应用于棉织物的拒水拒油整理.用红外光谱对聚合物进行表征,研究了交联剂对胶膜接触角及整理棉织物拒水拒油性能的影响.结果表明:未加交联剂,胶膜接触角达111.58°;加2%的三官能团氮丙啶交联剂,胶膜接触角可以提高到118.35°.经该乳液整理后的织物不仅具有较好的拒水性能,而且有突出的拒油性能,拒水达100分,拒油达6级;同时,耐久性良好,水洗30次以后,拒水为90分,拒油为5级.%Cationic fluorinated acrylic emulsions were synthesized with methyl methacrylate, isobornyl ac⁃rylate, lauryl methacrylate, hexafluorobutyl acrylate, butylene glycol dimethacrylate, 3- chloro- 2- hydroxypropyl methacrylate as monomers and azobis isobutyl amidine hydrochloride as the initiator, which was applied in wa⁃ter and oil repel ent finishing of cotton fabrics. The polymer emulsion properties were characterized with infra⁃red spectrometer. The effects of the crosslinking agent on the contact angle of the film and the water and oil repel ent properties of the finished fabrics were investigated. The results showed that the contact angle of the film was 111.58°, when 2% tri- functional aziridine crosslinking agent was added, the contact angle of the film was increased to 118.35°. The results showed that the finished fabric not only had good water repel ence but also had outstanding oil repel ence. The waterproofing level was 100 points, the oil repel ent level was grade 6; at the same time, the durability was excellent, after 30 times of washing, the waterproofing level was 90 points, and the oil repel ent level was grade 5.

  3. Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis

    International Nuclear Information System (INIS)

    -positive according to [3H]oestradiol-binding assay (dextran-coated charcoal [DCC]) were subjected to hydroxylapatite adsorption. ER isoforms covalently labeled with [125I]tamoxifen aziridine (TAZ) released from this matrix with 0.5 mol/l KCl were subsequently immunoprecipitated with a panel of monoclonal antibodies raised against various domains of ER (H222 [E], H226 [C] or ER1D5 [AB]) before being subjected to SDS-gel electrophoresis. Three approaches were used to identify the origins of the cleaved ER forms: potential truncated ER-α messenger RNAs that may encode ER isoforms of low molecular weights (Northern blot assay) were sought by using ER-α full-length probe; heat treatment of tumour cytosols in the absence or presence of a cocktail of protease inhibitors was performed; and the molecular weight of intracellular ER molecules was determined by in situ [125I]TAZ-labelling, which minimizes ER proteolysis. Breast cancer samples classified as ER-positive according to both biochemical (cytosolic DCC assay) and histochemical (ER1D5 monoclonal antibody) criteria were labelled with [3H]oestradiol and were subsequently subjected to hydroxylapatite adsorption. Hydroxylapatite extraction index (EI) is defined as a ratio of the specifically bound [3H]oestradiol released from the hydroxylapatite matrix with KCl to the total amount of the specifically bound [3H]oestradiol extracted successively with KCl and ethanol: EI= ([3H]oestradiol) [KCl] × 100/([3H]oestradiol) [KCl] + ([3H]oestradiol) [EtOH]. The EI was calculated for each cytosol in order to evaluate the amount of cleaved ER forms present. Persistence of adsorption ER to hydroxylapatite in the presence of KCl (low EI) and ER1D5 positivity established by immunohistochemistry are two independent criteria for the presence of amino-terminal ABC domains. We therefore assessed whether hydroxylapatite determinations performed on cytosols are related to immuno-histochemistry data. Cytosol pools labelled with [125I]TAZ gave different