Cobalt(III)-Catalyzed C-H Amidation of Dehydroalanine for the Site-Selective Structural Diversification of Thiostrepton.

ABSTRACT: Thiostrepton is a potent antibiotic against a broad range of Gram-positive bacteria, but its medical applications have been limited by its poor aqueous solubility. In this work, the first C(sp² )-H amidation of dehydroalanine (Dha) residues was applied to the site selective modification of thiostrepton to prepare a variety of derivatives. Unlike all prior methods for the modification of thiostrepton, the alkene framework of the Dha residue is preserved and with complete selectivity for the Z-stereoisomer. Additionally, an aldehyde group was introduced by C-H amidation, enabling oxime ligation for the installation of an even greater range of functionality. The thiostrepton derivatives generally maintain antimicrobial activity, and importantly, eight of the derivatives displayed i

SUBMITTER: Scamp RJ 

PROVIDER: S-EPMC6940514 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature