Enantioselective Total Synthesis of (+)-Anthecularin

An enantioselective total synthesis of (+)-anthecularin, an antiplasmodial and antitrypanosomal sesquiterpene lactone, has been achieved in 3.9% overall yield through 18 steps from a known dibromo alcohol. The key features of the synthesis include an intramolecular Claisen-type cyclization of a formyl-protected hydroxyl lactoneto construct a bicyclic intermediate with a quaternary stereogenic center and a stereocontrolled 1,2-addition of vinyllithium to a methoxyethyl-protected spirocyclic hydroxyl enoneto install a tetrasubstituted asymmetric centerwith excellentdiastereoselection. This first enantioselective synthesisof anthecularin enabled the determination of its absolute configurationas 2R, 3R, 4S, 8R.