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IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Aziridines; Carcinogenicity Tests; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Occupational Exposure
PubMed: 10476450
DOI: No ID Found -
European Journal of Medicinal Chemistry Sep 2009The present review describes research on natural aziridine alkaloids isolated from both terrestrial and marine species, as well as their lipophilic semi-synthetic,... (Review)
Review
The present review describes research on natural aziridine alkaloids isolated from both terrestrial and marine species, as well as their lipophilic semi-synthetic, and/or synthetic analogs. Over 130 biologically active aziridine-containing compounds demonstrate confirmed pharmacological activity including antitumor, antimicrobial, antibacterial effects. The structures, origin, and biological activities of aziridine alkaloids are reviewed. Consequently this review emphasizes the role of aziridine alkaloids as an important source of drug prototypes and leads for drug discovery.
Topics: Alkaloids; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Aziridines; Humans
PubMed: 19540628
DOI: 10.1016/j.ejmech.2009.05.013 -
Molecules (Basel, Switzerland) Mar 2022A short synthetic route to stereoselective access to -glycosyl-aminoethyl sulfide derivatives has been developed through the reaction of tributhyltin derivatives of...
A short synthetic route to stereoselective access to -glycosyl-aminoethyl sulfide derivatives has been developed through the reaction of tributhyltin derivatives of glycals with aziridinecarboaldehyde and the regioselective ring opening of a chiral aziridine with thiophenol. The absolute configurations of the resulting diastereoisomers were determined by 1H NMR spectroscopy.
Topics: Aziridines; Stereoisomerism; Sulfides
PubMed: 35335129
DOI: 10.3390/molecules27061764 -
Journal of the American Chemical Society Sep 2022Natural products containing an aziridine ring, such as mitomycin C and azinomycin B, exhibit antitumor activities by alkylating DNA via their aziridine rings; however,...
Natural products containing an aziridine ring, such as mitomycin C and azinomycin B, exhibit antitumor activities by alkylating DNA via their aziridine rings; however, the biosynthetic mechanisms underlying the formation of these rings have not yet been elucidated. We herein investigated the biosynthesis of vazabitide A, the structure of which is similar to that of azinomycin B, and demonstrated that Vzb10/11, with no similarities to known enzymes, catalyzed the formation of the aziridine ring via sulfate elimination. To elucidate the detailed reaction mechanism, crystallization of Vzb10/11 and the homologous enzyme, AziU3/U2, in the biosynthesis of azinomycin B was attempted, and the structure of AziU3/U2, which had a new protein fold overall, was successfully determined. The structural analysis revealed that these enzymes adjusted the dihedral angle between the amino group and the adjacent sulfate group of the substrate to almost 180° and enhanced the nucleophilicity of the C6-amino group temporarily, facilitating the S2-like reaction to form the aziridine ring. The present study reports for the first time the molecular basis for aziridine ring formation.
Topics: Aziridines; DNA; Mitomycin; Sulfates
PubMed: 35998388
DOI: 10.1021/jacs.2c07243 -
Nature Aug 2021Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards...
Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards ring-opening reactions makes them versatile precursors of diverse amine products, and, in some cases, the aziridine functional group itself imbues important biological (for example, anti-tumour) activity. Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy, but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles. Here we show that unactivated alkenes can be electrochemically transformed into a metastable, dicationic intermediate that undergoes aziridination with primary amines under basic conditions. This new approach expands the scope of readily accessible N-alkyl aziridine products relative to those obtained through existing state-of-the-art methods. A key strategic advantage of this approach is that oxidative alkene activation is decoupled from the aziridination step, enabling a wide range of commercially available but oxidatively sensitive amines to act as coupling partners for this strain-inducing transformation. More broadly, our work lays the foundations for a diverse array of difunctionalization reactions using this dication pool approach.
Topics: Alkenes; Amines; Aziridines; Chemistry Techniques, Synthetic; Electrochemistry; Oxidation-Reduction; Thermodynamics
PubMed: 34157720
DOI: 10.1038/s41586-021-03717-7 -
Acta Chimica Slovenica Jun 2022Optimized conditions for the synthesis of fully deprotected (2R)-aziridine containing dipeptides are described. Preparation of fully protected N- and C- terminal...
Optimized conditions for the synthesis of fully deprotected (2R)-aziridine containing dipeptides are described. Preparation of fully protected N- and C- terminal aziridine containing dipeptides was found to be straightforward and high yielding for the majority of compounds, whereas their full deprotection was possible only for C-terminal analogs. Deprotection of N-terminal derivatives using standard procedures of peptide chemistry was found difficult providing only mixtures of unidentifiable products. The described molecules have potential as building blocks in synthetic chemistry, in the chemical biology arena, as covalent modifiers, and as biomarkers.
Topics: Aziridines; Dipeptides
PubMed: 35861086
DOI: 10.17344/acsi.2021.6673 -
International Journal of Molecular... Dec 2021-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective...
-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective to amide carbonyl at a low (-78 °C) temperature. These ketones, in reaction with organolithium reagents, give symmetrical and unsymmetrical aziridinyl carbinols. The usage of excess phenyllithium may serve as a special N-Boc-protecting group cleavage method for acid-sensitive substrates.
Topics: Aziridines; Ketones; Lithium; Methanol; Molecular Structure; Organometallic Compounds; Stereoisomerism
PubMed: 34884949
DOI: 10.3390/ijms222313145 -
European Journal of Medicinal Chemistry Oct 2020Ficellomycin is an aziridine-containing antibiotic, produced by Streptomyces ficellus. Based on the newly identified ficellomycin gene cluster and the assigned functions...
Ficellomycin is an aziridine-containing antibiotic, produced by Streptomyces ficellus. Based on the newly identified ficellomycin gene cluster and the assigned functions of its genes, a possible pathway for aziridine ring formation in ficellomycin was proposed, which is a complex process involving at least 3 enzymatic steps. To obtain support for the proposed mechanism, the targeted genes encoding sulfate adenylyltransferase, adenylsulfate kinase, and a putative sulfotransferase were respectively disrupted and the subsequent analysis of their fermentation products revealed that all the three genes were involved in aziridine formation. To further confirm the mechanism, the key gene encoding a putative sulfotransferase was over expressed in Escherichia coli Rosseta (DE3). Enzyme assays indicated that the expressed sulfotransferase could specifically transfer a sulfo group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto the hydroxyl group of (R)-(-)-2-pyrrolidinemethanol. This introduces a good leaving group in the form of the sulfated hydroxyl moiety, which is then converted into an aziridine ring through an intramolecular nucleophilic attack by the adjacent secondary amine. The sulfation/intramolecular cyclization reaction sequence maybe a general strategy for aziridine biosynthesis in microorganisms. Discovery of this mechanism revealed an enzyme-catalyzed route for the synthesis of aziridine-containing reagents and provided an important insight into the functional diversity of sulfotransferases.
Topics: Aziridines; Catalysis; Cyclization; Drug Design; Electrophoresis, Polyacrylamide Gel; Enzymes; Fermentation; Genes, Bacterial; Intercellular Signaling Peptides and Proteins; Multigene Family; Streptomyces; Substrate Specificity
PubMed: 32712437
DOI: 10.1016/j.ejmech.2020.112639 -
Journal of the American Chemical Society Mar 2023Aziridines are compounds with a nitrogen-containing three-membered ring. When it is incorporated into natural products, the reactivity of the strained ring often drives...
Aziridines are compounds with a nitrogen-containing three-membered ring. When it is incorporated into natural products, the reactivity of the strained ring often drives the biological activities of aziridines. Despite its importance, the enzymes and biosynthetic strategies deployed to install this reactive moiety remain understudied. Herein, we report the use of methods to identify enzymes with potential aziridine-installing (aziridinase) functionality. To validate candidates, we reconstitute enzymatic activity and demonstrate that an iron(IV)-oxo species initiates aziridine ring closure by the C-H bond cleavage. Furthermore, we divert the reaction pathway from aziridination to hydroxylation using mechanistic probes. This observation, isotope tracing experiments using HO and O, and quantitative product analysis, provide evidence for the polar capture of a carbocation species by the amine in the pathway to aziridine installation.
Topics: Iron; Aziridines; Hydroxylation; Catalysis
PubMed: 36913534
DOI: 10.1021/jacs.2c12664 -
Organic Letters Apr 2020A straightforward synthesis of enantiopure α-trifluoromethyl aziridine-2-carboxylic acid (α-TfmAzy) is reported from a trifluoropyruvate derived enantiopure...
A straightforward synthesis of enantiopure α-trifluoromethyl aziridine-2-carboxylic acid (α-TfmAzy) is reported from a trifluoropyruvate derived enantiopure oxazolidine. A key Strecker-type synthetic step and a late cyanide basic hydrolysis gave the target compounds in six steps and 41% yield. A final peptide coupling was performed to demonstrate the usefulness of this highly constrained fluorinated unnatural amino acid.
Topics: Aziridines; Hydrocarbons, Fluorinated; Molecular Structure; Peptides; Stereoisomerism
PubMed: 32216364
DOI: 10.1021/acs.orglett.0c00645