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

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.