Entry into C1 Hydroxylated Discorhabdins

Abstract

The discorhabdins are a unique class of marine natural products that have emerged as promising hypoxia-inducible factor 1 inhibitors. Despite the most potent discorhabdin possessing C1 hydroxylation, there remain no syntheses that install this functionality. Herein we report the facile and stereoselective installation of this distinctive alcohol, and the synthesis of 14-bromo-1-hydroxydiscorhabdin V. This represents the first example of C1 alcohol installation on the discorhabdin framework, enabling newfound access to hydroxylated discorhabdins and analogs.