Total Synthesis and Structural Reassignment of the Antitubercular Natural Product Evybactin.

ABSTRACT: The escalating threat posed by antibiotic resistance is a global concern and underscores the need for new antibiotics. In this context, the recent discovery of evybactin, a nonribosomal depsipeptide antibiotic that selectively and potently inhibits the growth of M. tuberculosis, is particularly noteworthy. Here, we present the first total synthesis of this natural product, along with a revision of its assigned structure. Our studies revealed a disparity between the structure originally proposed for evybactin and its actual configuration. Specifically, the 3-methylhistidine residue present in the evybactin core macrocycle was found to be of the d-configuration rather than the previously assigned l-His(Me). Having addressed this, we further optimized our solid-phase synthetic route to provid

SUBMITTER: Lysenko V 

PROVIDER: S-EPMC11711294 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature