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Organic & Biomolecular Chemistry Oct 2005The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through...
The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through conjugate addition of benzylamine and in situ intramolecular nucleophilic expulsion of bromine. The regioselective aziridine ring-opening, using water as a nucleophile, resulted in the alpha-hydroxy-beta-aminoester 6, which was exploited in the synthesis of six and five membered azasugars 1b/1c and 2b/2c, respectively. The glycosidase inhibitory activity of the title compounds was evaluated.
Topics: Alkaloids; Aziridines; Crystallography, X-Ray; Enzyme Activation; Enzyme Inhibitors; Glucose; Glycoside Hydrolases; Models, Molecular; Molecular Structure; Piperidines; Pyrrolidines; Stereoisomerism; Structure-Activity Relationship
PubMed: 16211108
DOI: 10.1039/b509216g -
The Journal of Organic Chemistry Oct 2015The generation of common and stereochemically rich medium-sized benzo-fused sultams via complementary pairing of heretofore-unknown (o-fluoroaryl)sulfonyl aziridine...
The generation of common and stereochemically rich medium-sized benzo-fused sultams via complementary pairing of heretofore-unknown (o-fluoroaryl)sulfonyl aziridine building blocks with an array of amino alcohols/amines in a modular one-pot, sequential protocol using an aziridine ring opening and intramolecular nucleophilic aromatic substitution is reported. The strategy employs a variety of amino alcohols/amines and proceeds with 6 + 4/6 + 5 and 6 + 1 cycloetherification pathways in a highly chemo- and regioselective fashion to obtain skeletally and structurally diverse, polycyclic, 10- to 11- and 7-membered benzo-fused sultams for broad-scale screening.
Topics: Aziridines; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Naphthalenesulfonates
PubMed: 26446396
DOI: 10.1021/acs.joc.5b01429 -
Organic Letters Nov 2015A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide...
A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.
Topics: Aza Compounds; Aziridines; Catalysis; Esters; Molecular Structure; Stereoisomerism
PubMed: 26558319
DOI: 10.1021/acs.orglett.5b02838 -
Chemical & Pharmaceutical Bulletin Dec 2010Guanidines are categorized as strong organobases; however, their catalytic utility in organic synthesis has not been discussed thoroughly. The author's group has... (Review)
Review
Guanidines are categorized as strong organobases; however, their catalytic utility in organic synthesis has not been discussed thoroughly. The author's group has extensively and systematically studied their potential ability focusing on: 1) modified guanidines as chiral auxiliaries; 2) guanidinium ylides for aziridine formation; 3) the affinity of bisguanidine for proton and metal salts; and 4) the potential chirality of bisguanidine. Under the first topic, a variety of chiral guanidines was designed by the introduction of chirality on the three guanidinyl nitrogens, and the modified guanidines prepared using our original methods were found to be effective not only in catalytic but also in stoichiometric asymmetric syntheses. Under the second topic, the reaction of guanidinium salts carrying a glycinate function with aromatic or unsaturated aldehydes under basic conditions unexpectedly afforded aziridine-2-carboxylates, which were available as useful building blocks in organic synthesis due to their convertibility to functionalized amino acid derivatives in the ring-opening reaction, together with urea compounds recyclable to the starting guanidinium salts. The introduction of a chiral template to the guanidinium salt allowed us to expand the cyclic aziridination reaction to an asymmetric version. Under the third topic, effective complexabilty of bisguanidines with either proton or metal ions in water was observed, suggesting their possible application to the removal of toxic substances from polluted water and recovery of rare elements as material sources. Under the final topic, monomethylation or monoethylation of bisguanidine afforded a chiral product via asymmetric crystallization, indicating that bisguanidines have a potential chiral character due to the plane asymmetry.
Topics: Alkylation; Aziridines; Catalysis; Guanidines; Stereoisomerism
PubMed: 21139254
DOI: 10.1248/cpb.58.1555 -
Biochemical and Biophysical Research... Aug 1989A new mechanism-based glucosidase inactivator, conduritol aziridine (1,2-dideoxy-1,2-epimino-myo-inositol), has been synthesised from myo-inositol. This aziridine...
A new mechanism-based glucosidase inactivator, conduritol aziridine (1,2-dideoxy-1,2-epimino-myo-inositol), has been synthesised from myo-inositol. This aziridine inactivates both the beta-glucosidase from Alcaligenes faecalis and the alpha-glucosidase from yeast according to the expected pseudo-first order kinetics. Inactivation constants measured are Ki = 3.0mM, ki = 0.077 min-1 for the beta-glucosidase, and Ki = 9.5mM, ki = 0.39 min-1 for the alpha-glucosidase. Evidence for irreversible inactivation is provided by the lack of reactivation upon dilution of inactivated enzyme into buffer containing substrate.
Topics: Alcaligenes; Aziridines; Azirines; Glucosidases; Imino Pyranoses; Inositol; Saccharomyces cerevisiae; Structure-Activity Relationship
PubMed: 2673241
DOI: 10.1016/0006-291x(89)92164-5 -
Chemical Communications (Cambridge,... Oct 2013A concise synthesis of the macroline-related alkaloid (±)-alstonerine is reported. Key steps are regioselective and stereospecific aziridine ring-opening using a...
A concise synthesis of the macroline-related alkaloid (±)-alstonerine is reported. Key steps are regioselective and stereospecific aziridine ring-opening using a sulfone-stabilised carbanion, Me3Al-mediated O → N-transacylation-elimination, intramolecular Michael reaction, and one-pot reduction-dehydration-Pictet-Spengler cyclisation.
Topics: Aziridines; Crystallography, X-Ray; Cyclization; Indole Alkaloids; Molecular Conformation; Stereoisomerism
PubMed: 23999623
DOI: 10.1039/c3cc45543b -
Molecular Diversity May 2018Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great... (Review)
Review
Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great effort has been put forward by scientists toward unique bond construction methodologies via ring opening of aziridines. In this regard, a wide range of chiral metal- and organo-catalyzed desymmetrization reactions of aziridines have been reported with carbon, sulfur, oxygen, nitrogen, halogen, and other nucleophiles. In this review, an outline of methodologies adopted by a number of scientists during 2013-2017 for aziridine ring opening reactions as well as their synthetic applications is described.
Topics: Aziridines; Stereoisomerism
PubMed: 29728870
DOI: 10.1007/s11030-018-9829-0 -
The Journal of Organic Chemistry Jul 2012Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these...
Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these molecules, brought together by a weak and reversible aminal "connection", was found to be an important element of reactivity control. We present evidence that reversible dimer dissociation is instrumental in aziridine aldehyde transformations. We anticipate further developments that will unveil other synthetic consequences of remote control of selectivity through forging reversible covalent interactions.
Topics: Aldehydes; Aziridines; Dimerization; Molecular Conformation; Stereoisomerism
PubMed: 22662756
DOI: 10.1021/jo3007418 -
Chemico-biological Interactions 1987To clarify the relationship of aziridine biotransformation to their cytotoxic activities, the metabolism of optical isomers of typical cytotoxic and non-cytotoxic...
To clarify the relationship of aziridine biotransformation to their cytotoxic activities, the metabolism of optical isomers of typical cytotoxic and non-cytotoxic aziridines was studied in isolated hepatocytes, rat liver microsomes, mitochondria and L-1210 mouse leukemia cells. Cytotoxic 1-methyl-2-beta-naphthylaziridine (NAZ) gave nitrosomethane as one of the bioactivation products in isolated hepatocytes and simultaneously induced a marked decrease in cellular ATP followed by cell lethality. NAZ itself did not directly affect the respiratory function of mitochondria in isolated hepatocytes or in buffer solution, however, it inhibited the mitochondrial activity in the presence of microsomes in the buffer solution. Nitroso-t-butane or nitrosomethane dimer, used as a substitute for extremely labile nitrosomethane, strongly inhibited the respiration of mitochondria. On the other hand, optical isomers of 2-aziridinecarboxylic acid (AZC) which did not give nitrosomethane in isolated hepatocytes or microsomes also did not show cytotoxicity. Thus, the cytotoxicity of NAZ seems to be induced by bioactivation via cellular oxidases with the nitrosomethane generated being a major toxic component. This may occur with most of the cytotoxic aziridine derivatives.
Topics: Adenosine Triphosphate; Animals; Aziridines; Azirines; Biotransformation; Cell Survival; Isomerism; Leukemia L1210; Male; Mice; Microsomes, Liver; Oxygen Consumption; Rats; Rats, Inbred Strains
PubMed: 3664792
DOI: 10.1016/0009-2797(87)90096-2 -
FEBS Letters Mar 1992The three-membered ring of aziridine-2-carboxylic acid, which is susceptible to opening by nucleophiles, has been analyzed as a potential useful handle for the design of...
The three-membered ring of aziridine-2-carboxylic acid, which is susceptible to opening by nucleophiles, has been analyzed as a potential useful handle for the design of specific irreversible inhibitors of cysteine proteinases. For this thiol-reactive amino acid, an imino analogue of proline, a second-order rate constant of 17.07 M-1.s-1 for inactivation of papain was determined. Thus, the aziridine moiety proved to be remarkably more reactive than activated double bonds, e.g. N-ethylmaleimide, or halides such as alpha-iodopropionic acid or chloroacetic acid. Since it does not alkylate histidine under conditions in which quantitative alkylation occurs with N-ethyl-maleimide, it could represent an interesting reactive amino acid unit for the synthesis of a new class of irreversible inhibitors, at least in terms of specificity of the chemical reaction involved in the inactivation process.
Topics: Aziridines; Kinetics; Papain
PubMed: 1544473
DOI: 10.1016/0014-5793(92)80098-2