Stereochemical assignment of topsentolide C2 by stereodivergent synthesis of its four diastereomers

Four diastereomers of topsentolide C2, a cytotoxic nine-membered lactone isolated from the marine sponge Topsentia sp., were synthesized stereodivergently from a common chiral seco acid by the combined use of the Yamaguchi and Mitsunobu lactonizations. Comparison of the NMR spectra of the four diastereomers with those of an authentic sample of topsentolide C2 led to the stereochemical determination of topsentolide C2 as 8R, 11S, and 12S.