Synthesis of topsentolides A2 and C2, and non-enzymatic conversion of the former to the latter

Abstract

The first total synthesis of the marine-derived cytotoxin topsentolide A2, which eventually culminated in its stereochemical determination, was accomplished in 17 steps from a known chiral alcohol. An improved synthesis of its congener, topsentolide C2, from a synthetic intermediate of topsentolide A2 was also performed by utilizing the Yamaguchi lactonization to construct its nine-membered lactone ring. Treatment of epoxide ring-containing topsentolide A2 with HCl/MeOH brought about its quantitative conversion into topsentolide C2.