RESUMO
Only 0.016 % of all known natural products contain an aziridine ring, but this unique structural feature imparts high reactivity and cytotoxicity to the compounds in which it is found. Until 2021, no naturally occurring aziridine-forming enzymes had been identified. Since 2021, the biosynthetic enzymes for ~10 % of known aziridine containing natural products have been identified and characterized. This article describes the recent advances in our understanding of enzyme-catalyzed aziridine formation in the context of historical methods for aziridine formation through synthetic chemistry.
RESUMO
N-Nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate (N-nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite the importance of this structural motif, knowledge of its biosynthesis is limited. Herein we describe the discovery of a biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing the diazeniumdiolate natural product l-alanosine. Gene disruption and stable isotope feeding experiments identified essential biosynthetic genes and revealed the source of the N-nitroso group. Additional biochemical characterization of the biosynthetic enzymes revealed that the non-proteinogenic amino acid l-2,3-diaminopropionic acid (l-Dap) is synthesized and loaded onto a free-standing peptidyl carrier protein (PCP) domain in l-alanosine biosynthesis, which we propose may be a mechanism of handling unstable intermediates generated enâ route to the diazeniumdiolate. These discoveries will facilitate efforts to determine the biochemistry of diazeniumdiolate formation.
Assuntos
Alanina/análogos & derivados , Compostos Azo/metabolismo , Proteínas de Bactérias/metabolismo , Vias Biossintéticas , Família Multigênica , Streptomyces/metabolismo , Alanina/metabolismo , Proteínas de Bactérias/genética , Estrutura Molecular , Streptomyces/genéticaRESUMO
Described herein are synthetic efforts toward the synthesis of hippolachnin A. Two independently devised routes from the Brown and Wood groups allowed for the synthesis of hippolachnin A from the unusual starting material, quadricyclane, by harnessing the power of late-stage C-H oxidation. Collaborative union of the best features of the two routes allowed for preparation of the molecule with improved efficiency.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Reação de Cicloadição , Policetídeos/síntese química , Carbono/química , Hidrogênio/química , Conformação Molecular , Oxirredução , Policetídeos/química , EstereoisomerismoRESUMO
This manuscript describes the enantioselective preparation of a spirooxindole that is suited for advancedment to either Citrinadin A or B.
RESUMO
This manuscript describes an enantioselective synthesis of the naturally occurring alkaloid citrinadin B. The synthetic effort revealed an anomaly in the original structural assignment that has led to the proposal of a stereochemical revision. This revision is consistent with the structures previously reported for a closely related family of alkaloids, PF1270A-C. The synthesis is convergent and employs a stereoselective intermolecular nitrone cyloaddition reaction as a key step.
Assuntos
Alcaloides Indólicos/química , Alcaloides Indólicos/síntese química , Compostos Orgânicos , Estereoisomerismo , Especificidade por SubstratoRESUMO
This manuscript describes the preparation of an advanced intermediate toward the total synthesis of citrinadin A, featuring a [3+2] cycloaddition employing in situ generation of the dipole.