Modular Total Synthesis and Antimycobacterial Activity of Rufomycins

IF 4.9 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2024-12-09 DOI:10.1021/acs.orglett.4c0416310.1021/acs.orglett.4c04163

Max J. Bedding, Bryton C. Forster, Andrew M. Giltrap, Maxwell T. Stevens, Leo Corcilius, Warwick J. Britton and Richard J. Payne*,

引用次数: 0

Abstract

The rufomycins are a family of nonribosomal cyclic peptides isolated from the deep sea-dwelling Streptomyces atratus. Herein, we describe the total synthesis of six congeners in the rufomycin family. Synthesis was achieved through a modular solid-phase strategy, incorporating synthetic nonproteinogenic amino acids: l-2-amino-4-hexenoic acid, tert-prenyl-l-tryptophan (and related (S)-epoxide), and N-methyl-δ-hydroxy-l-leucine. Following macrolactamization, these peptides were further diversified through late-stage oxidation and secondary cyclization to furnish a library of six synthetic natural products. Rufomycins 4 and 22, bearing an unusual 6-hydroxypiperidin-2-one structural motif, exhibited impressive activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC₅₀ = 350–670 nM).

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.