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Molecules (Basel, Switzerland) Oct 2017Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed... (Review)
Review
Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines, azepanes and azocanes. This review highlights some facile and green synthetic routes for the synthesis of unsubstituted, multisubstituted and highly functionalized saturated cyclic amines including one-pot, microwave assisted, metal-free, solvent-free and in aqueous media.
Topics: Amines; Aziridines; Chemistry Techniques, Synthetic; Cyclization; Green Chemistry Technology; Microwaves; Nitrogen; Piperidines; Pyrrolidines
PubMed: 29023406
DOI: 10.3390/molecules22101691 -
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 -
British Medical Journal Jun 1955
Topics: Hodgkin Disease; Leukemia; Lymphoma; Triazines; Triethylenemelamine
PubMed: 14363905
DOI: No ID Found -
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 -
Journal of the American Chemical Society Nov 2022Aziridines are readily available C(sp) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology...
Aziridines are readily available C(sp) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology for C(sp)-C(sp) cross-coupling between aziridines and methyl/1°/2° aliphatic alcohols activated as benzaldehyde dialkyl acetals. Orthogonal activation modes of each alkyl coupling partner facilitate cross-selectivity in the C(sp)-C(sp) bond-forming reaction: the benzaldehyde dialkyl acetal is activated via hydrogen atom abstraction and β-scission via a bromine radical (generated in situ from single-electron oxidation of bromide), whereas the aziridine is activated at the Ni center via reduction. We demonstrate that an Ni(II) azametallacycle, conventionally proposed in aziridine cross-coupling, is not an intermediate in the productive cross-coupling. Rather, stoichiometric organometallic and linear free energy relationship studies indicate that aziridine activation proceeds via Ni(I) oxidative addition, a previously unexplored elementary step.
Topics: Acetals; Catalysis; Benzaldehydes; Nickel; Aziridines
PubMed: 36256882
DOI: 10.1021/jacs.2c09294 -
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 -
Journal of Natural Medicines Jan 2024Epoxides, aziridines, and cyclopropanes are found in various medicinal natural products, including polyketides, terpenes, peptides, and alkaloids. Many classes of... (Review)
Review
Epoxides, aziridines, and cyclopropanes are found in various medicinal natural products, including polyketides, terpenes, peptides, and alkaloids. Many classes of biosynthetic enzymes are involved in constructing these ring structures during their biosynthesis. This review summarizes our current knowledge regarding how α-ketoglutarate-dependent nonheme iron enzymes catalyze the formation of epoxides, aziridines, and cyclopropanes in nature, with a focus on enzyme mechanisms.
Topics: Iron; Ketoglutaric Acids; Catalysis; Cyclopropanes; Aziridines; Epoxy Compounds
PubMed: 37980694
DOI: 10.1007/s11418-023-01760-4 -
ChemistryOpen Jun 2024In previous works, we demonstrated that tertiary 3-chloropiperidines are potent chemotherapeutics, alkylating the DNA through the formation of bicyclic aziridinium ions....
In previous works, we demonstrated that tertiary 3-chloropiperidines are potent chemotherapeutics, alkylating the DNA through the formation of bicyclic aziridinium ions. Herein, we report the synthesis of novel secondary 3-chloropiperidine analogues. The synthesis incorporates a new procedure to monochlorinate unsaturated primary amines utilizing N-chlorosuccinimide, while carefully monitoring the temperature to prevent dichlorination. Furthermore, we successfully isolated highly strained bicyclic aziridines by treating the secondary 3-chloropiperidines with a sufficient amount of base. We conclude this work with a DNA cleavage assay as a proof of principle, comparing our previously known substrates to the novel compounds. In this, the secondary 3-chloropiperidine as well as the isolated bicyclic aziridine, proved to be more effective than their tertiary counterpart.
Topics: Piperidines; Antineoplastic Agents, Alkylating; Alkylating Agents; DNA Cleavage; Humans; Aziridines; DNA; Succinimides
PubMed: 38088585
DOI: 10.1002/open.202300181 -
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 -
Organic Letters May 2020Piperazines are prevalent in pharmaceuticals and natural products, but traditional methods do not typically introduce stereochemical complexity into the ring. To expand...
Piperazines are prevalent in pharmaceuticals and natural products, but traditional methods do not typically introduce stereochemical complexity into the ring. To expand access to these scaffolds, we report Rh-catalyzed ring expansions of aziridines and sulfonyl-1,2,3-triazoles to furnish dehydropiperazines with excellent diastereocontrol. Productive ring expansion proceeds via a pseudo-1,4-sigmatropic rearrangement of an aziridinium ylide species. However, the structural features of the carbene precursor are important, as pyridotriazoles undergo competing cheletropic extrusion to furnish ketimines.
Topics: Aziridines; Catalysis; Imines; Molecular Structure; Nitriles; Piperazines; Rhodium; Triazoles
PubMed: 32320259
DOI: 10.1021/acs.orglett.0c01124