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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 -
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 -
National Science Review Oct 2023Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the...
Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.
PubMed: 38059062
DOI: 10.1093/nsr/nwad187 -
Molecules (Basel, Switzerland) Feb 2019Small ring heterocycles, such as epoxides and aziridines, are present in several natural products and are also highly versatile building blocks, frequently involved in... (Review)
Review
Small ring heterocycles, such as epoxides and aziridines, are present in several natural products and are also highly versatile building blocks, frequently involved in the synthesis of numerous bioactive products and pharmaceuticals. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures, multicomponent reactions (MCRs) have been explored in the synthesis and ring opening of these heterocyclic units. In this review, the recent advances in MCRs involving the synthesis and applications of epoxides and aziridines to the preparation of other heterocycles are discussed emphasizing the stereoselectivity of the reactions.
Topics: Aziridines; Biological Products; Epoxy Compounds; Green Chemistry Technology; Molecular Structure; Stereoisomerism
PubMed: 30754666
DOI: 10.3390/molecules24030630 -
Chinese Journal of Cancer Feb 2014Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain... (Review)
Review
Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.
Topics: Anthraquinones; Antineoplastic Agents; Aziridines; Cell Hypoxia; Humans; Indolequinones; Molecular Structure; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Nitrogen Mustard Compounds; Nitroimidazoles; Phosphoramide Mustards; Prodrugs; Tirapazamine; Triazines
PubMed: 23845143
DOI: 10.5732/cjc.012.10285 -
Molecular & Cellular Proteomics : MCP Oct 2014Plants produce hundreds of glycosidases. Despite their importance in cell wall (re)modeling, protein and lipid modification, and metabolite conversion, very little is...
Plants produce hundreds of glycosidases. Despite their importance in cell wall (re)modeling, protein and lipid modification, and metabolite conversion, very little is known of this large class of glycolytic enzymes, partly because of their post-translational regulation and their elusive substrates. Here, we applied activity-based glycosidase profiling using cell-permeable small molecular probes that react covalently with the active site nucleophile of retaining glycosidases in an activity-dependent manner. Using mass spectrometry we detected the active state of dozens of myrosinases, glucosidases, xylosidases, and galactosidases representing seven different retaining glycosidase families. The method is simple and applicable for different organs and different plant species, in living cells and in subproteomes. We display the active state of previously uncharacterized glycosidases, one of which was encoded by a previously declared pseudogene. Interestingly, glycosidase activity profiling also revealed the active state of a diverse range of putative xylosidases, galactosidases, glucanases, and heparanase in the cell wall of Nicotiana benthamiana. Our data illustrate that this powerful approach displays a new and important layer of functional proteomic information on the active state of glycosidases.
Topics: Arabidopsis; Arabidopsis Proteins; Aziridines; Catalytic Domain; Cell Wall; Cyclohexanols; Glycoside Hydrolases; Mass Spectrometry; Molecular Probes; Phylogeny; Proteomics
PubMed: 25056938
DOI: 10.1074/mcp.O114.041616 -
Nature Communications Jun 2022The activation of aziridines typically involves the use of strong Lewis acids or transition metals, and methods relying on weak interactions are rare. Herein, we report...
The activation of aziridines typically involves the use of strong Lewis acids or transition metals, and methods relying on weak interactions are rare. Herein, we report that cooperative chalcogen bonding interactions in confined sites can activate sulfonyl-protected aziridines. Among the several possible distinct bonding modes, our experiments and computational studies suggest that an activation mode involving the cooperative Se···O and Se···N interactions is in operation. The catalytic reactions between weakly bonded supramolecular species and nonactivated alkenes are considered as unfavorable approaches. However, here we show that the activation of aziridines by cooperative Se···O and Se···N interactions enables the cycloaddition of weakly bonded aziridine-selenide complex with nonactivated alkenes in a catalytic manner. Thus, weak interactions can indeed enable these transformations and are an alternative to methods relying on strong Lewis acids.
Topics: Alkenes; Aziridines; Chalcogens; Cycloaddition Reaction; Lewis Acids
PubMed: 35732663
DOI: 10.1038/s41467-022-31293-5 -
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 -
Molecules (Basel, Switzerland) Oct 2018Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable... (Review)
Review
Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent advances in the catalytic asymmetric transformations of oxaziridines, including oxidation, amination, cycloaddition and deracemization.
Topics: Amination; Aziridines; Catalysis; Cycloaddition Reaction; Molecular Structure
PubMed: 30332802
DOI: 10.3390/molecules23102656 -
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