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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 -
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 -
Organic & Biomolecular Chemistry Jun 2023Compounds featuring aziridine moieties are widely known and extensively reported in the literature. Due to their great potential from both synthetic and pharmacological... (Review)
Review
Compounds featuring aziridine moieties are widely known and extensively reported in the literature. Due to their great potential from both synthetic and pharmacological points of view, many researchers have focused their efforts on the development of new methodologies for the preparation and transformation of these interesting compounds. Over the years, more and more ways to obtain molecules bearing these three-membered functional groups, which are challenging due to their inherent reactivity, have been described. Among them, several are more sustainable. In this review, we report the recent advances in the biological and chemical evolution of aziridine derivatives, in particular, the variety of methodologies described for the synthesis of aziridines and their chemical transformations leading to the formation of interesting derivatives, such as 4-7 membered heterocycles of pharmaceutical interest due to their promising biological activities.
Topics: Aziridines
PubMed: 37218299
DOI: 10.1039/d3ob00424d -
Vaccine Nov 2001
Review
Topics: Aziridines; Foot-and-Mouth Disease Virus; Formaldehyde; Humans; Poliovirus; Vaccines, Attenuated; Viral Vaccines
PubMed: 11672893
DOI: 10.1016/s0264-410x(01)00342-5 -
ACS Chemical Biology Dec 2023GH127 and GH146 microorganismal retaining β-l-arabinofuranosidases, expressed by human gut microbiomes, feature an atypical catalytic domain and an unusual mechanism of...
GH127 and GH146 microorganismal retaining β-l-arabinofuranosidases, expressed by human gut microbiomes, feature an atypical catalytic domain and an unusual mechanism of action. We recently reported that both GH146 and HypBA1 are inhibited by β-l-furanosyl cyclophellitol epoxide, supporting the action of a zinc-coordinated cysteine as a catalytic nucleophile, where in most retaining GH families, an aspartate or glutamate is employed. This work presents a panel of β-l-furanosyl cyclophellitol epoxides and aziridines as mechanism-based GH146/HypBA1 inhibitors and activity-based probes. The β-l-furanosyl cyclophellitol aziridines both inhibit and label β-l-arabinofuranosidase efficiently (however with different activities), whereas the epoxide-derived probes favor GH146 over HypBA1. These findings are accompanied by X-ray structural analysis of the unmodified β-l-furanosyl cyclophellitol aziridine in complex with both isozymes, which were shown to react by nucleophilic opening of the aziridine, at the pseudoanomeric carbon, by the active site cysteine nucleophile to form a stable thioether bond. Altogether, our activity-based probes may serve as chemical tools for the detection and identification of low-abundance β-l-arabinofuranosidases in complex biological samples.
Topics: Humans; Cysteine; Glycoside Hydrolases; Aziridines; Epoxy Compounds
PubMed: 38051515
DOI: 10.1021/acschembio.3c00558 -
European Journal of Medicinal Chemistry 2013A series of new aziridines β-D-galactopyranoside derivatives were synthesized from alkenyl β-D-galactopyranosides employing Sharpless conditions. The structures of the...
A series of new aziridines β-D-galactopyranoside derivatives were synthesized from alkenyl β-D-galactopyranosides employing Sharpless conditions. The structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and elemental analysis. The stereoselectivity of the reaction and the structural requirements of the alkenyl precursor for improving diastereoisomeric excesses of the direct aziridination reaction were also studied. The new compounds were subjected to a preliminary screening for cytotoxic activity against human lung cancer cells vs. human non-malignant lung cells. Terminal aziridine derivatives showed activity and, most notably, selectivity. One of the most active and selective compounds was also evaluated against breast cancer cells, melanoma cells, and non-malignant cells from the same origin. Its cytotoxic activity was similar to that of the positive controls, displaying a highly selective cytotoxic activity against both types of cancer cells.
Topics: Antineoplastic Agents; Aziridines; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Galactose; Humans; MCF-7 Cells; Molecular Structure; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 24177365
DOI: 10.1016/j.ejmech.2013.10.020 -
The Journal of Organic Chemistry Dec 2017A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl...
A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give trans-aziridines in 73-90% yield with 82-99% ee and trans/cis selectivities of 19:1 to >99:1. The optimal protocol for the trans-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give trans-aziridines in 60-88% yield with 60-98% ee and trans/cis selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the cis- and not the trans-diastereomer. The aryl and aliphatic aldehydes both gave the trans-aziridines with the same absolute configuration with the same catalyst; however, in those cases where cis-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes.
Topics: Aziridines; Catalysis; Molecular Structure
PubMed: 29084386
DOI: 10.1021/acs.joc.7b02184 -
Nature Communications Jun 2022N-functionalized aziridines, which are both useful intermediates and important synthetic targets, can be envisioned as arising from the addition of nitrenes (i.e., NR...
N-functionalized aziridines, which are both useful intermediates and important synthetic targets, can be envisioned as arising from the addition of nitrenes (i.e., NR fragments) to olefinic substrates. The exceptional reactivity of most nitrenes, in particular with respect to unimolecular decomposition, prevents general application of nitrene-transfer to the synthesis of N-functionalized aziridines. Here we demonstrate N-aryl aziridine synthesis via 1) olefin aziridination with N-aminopyridinium reagents to afford N-pyridinium aziridines followed by 2) Ni-catalyzed C-N cross-coupling of the N-pyridinium aziridines with aryl boronic acids. The N-pyridinium aziridine intermediates also participate in ring-opening chemistry with a variety of nucleophiles to afford 1,2-aminofunctionalization products. Mechanistic investigations indicate aziridine cross-coupling proceeds via a noncanonical mechanism involving initial aziridine opening promoted by the bromide counterion of the Ni catalyst, C-N cross-coupling, and finally aziridine reclosure. Together, these results provide new opportunities to achieve selective incorporation of generic aryl nitrene equivalents in organic molecules.
Topics: Alkenes; Aziridines; Boronic Acids; Catalysis; Indicators and Reagents; Stereoisomerism
PubMed: 35689000
DOI: 10.1038/s41467-022-31032-w -
International Journal of Molecular... Oct 2022The ubiquitin-proteasome pathway (UPP) is the major proteolytic system in the cytosol and nucleus of all eukaryotic cells. The role of proteasome inhibitors (PIs) as...
The ubiquitin-proteasome pathway (UPP) is the major proteolytic system in the cytosol and nucleus of all eukaryotic cells. The role of proteasome inhibitors (PIs) as critical agents for regulating cancer cell death has been established. Aziridine derivatives are well-known alkylating agents employed against cancer. However, to the best of our knowledge, aziridine derivatives showing inhibitory activity towards proteasome have never been described before. Herein we report a new class of selective and nonPIs bearing an aziridine ring as a core structure. In vitro cell-based assays (two leukemia cell lines) also displayed anti-proliferative activity for some compounds. In silico studies indicated non-covalent binding mode and drug-likeness for these derivatives. Taken together, these results are promising for developing more potent PIs.
Topics: Humans; Proteasome Inhibitors; Proteasome Endopeptidase Complex; Antineoplastic Agents; Aziridines; Neoplasms; Alkylating Agents; Ubiquitins
PubMed: 36293216
DOI: 10.3390/ijms232012363 -
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