Total Synthesis of Aculeatin A via Double Intramolecular Oxa-Michael Addition of Secondary/Tertiary Alcohols

A new synthetic strategy was developed for a concise total synthesis of aculeatin A as a single spiroisomer in both racemic and enantioselective fashions in 8-10 steps with ∼10% overall yield from the known alkyne 11, featuring phenol oxidative dearomatization, double intramolecular oxa-Michael addition of secondary/tertiary alcohols, and chemo- and stereoselective reduction of ketone. The new synthetic strategy greatly expedites the access to the potent antiprotozoal aculeatin A, 6-epi-aculeatin D, and their analogues.