Total synthesis of clostrubin.

ABSTRACT: Clostrubin is a potent antibiotic against methicillin- and vancomycin-resistant bacteria that was isolated from a strictly anaerobic bacterium Clostridium beijerinckii in 2014. This polyphenol possesses a fully substituted arene moiety on its pentacyclic scaffold, which poses a considerable challenge for chemical synthesis. Here we report the first total synthesis of clostrubin in nine steps (the longest linear sequence). A desymmetrization strategy is exploited based on the inherent structural feature of the natural product. Barton-Kellogg olefination forges the two segments together to form a tetrasubstituted alkene. A photo-induced 6? electrocyclization followed by spontaneous aromatization constructs the hexasubstituted B ring at a late stage. In total, 200?mg of clostrubin are delivered through this approach.

SUBMITTER: Yang M 

PROVIDER: S-EPMC4382683 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature