Publication date: Dec 09, 2024
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 (MIC = 350-670 nM).
| Concepts | Keywords |
|---|---|
| Hydroxypiperidin | Activity |
| Library | Amino |
| Sea | Antimycobacterial |
| Tuberculosis | Cyclic |
| Virulent | Deep |
| Isolated | |
| Modular | |
| Nonribosomal | |
| Peptides | |
| Rufomycins | |
| Sea | |
| Synthesis | |
| Synthetic | |
| Total |
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Amino acids |
| disease | MESH | l-tryptophan |
| drug | DRUGBANK | L-Tryptophan |
| drug | DRUGBANK | L-Leucine |
| drug | DRUGBANK | Methyl isocyanate |