Stereoselective total synthesis of (+)-goniothalesdiol and (+)-2,5-epi-goniothalesdiol from D-mannitol

摘要

An efficient and practical total synthesis of (+)-goniothalesdiol and its 2,5-epi analogue is described herein. The key features include a diastereoselective reduction of C-5 keto with Zn(BH4)(2) to generate the desired stereochemistry at C-5. The tetrahydrofuran backbone of natural goniothalesdiol was synthesized under basic conditions via epoxide formation, followed by in situ 5-exo opening of the epoxide ring with 7-benzoyloxy oxygen upon debenzoylation. For the 2,5-epi analogue, the tetrahydrofuran ring was formed via acid-catalyzed acetonide deprotection followed by concomitant S(N)2 displacement of the O-mesyl group at C-5 center with C-2-gamma-oxygen.