A General Strategy to Elisabethane Diterpenes: Stereocontrolled Synthesis of Elisapterosin B via Oxidative Cyclization of an Elisabethin Precursor

Abstract

Described is an efficient synthesis of the complex bioactive natural product, elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb. The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a highly stereocontrolled sequence commencing with a simple glutamic acid derived compound. Pivotal steps in the sequence include (a) a pinacol-type ketal rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative cyclization of the elisabethin precursor to elisapterosin B.