Total Synthesis of 10-Deoxymethynolide, the Aglycon of the Macrolide Antibiotic 10-Deoxymethymycin

Abstract

A short and efficient total synthesis of 10-deoxymethynolide (2c), the aglycon of 10-deoxymethymycin (1c), has been accomplished in 16 steps and 12% overall yield from (S)-3-O-p-toluenesulfonyl-3-hydroxy-2-methylpropanal (15c). The synthesis features an expeditious preparation of (+)-5a, a synthetic equivalent of the Prelog−Djerassi lactonic acid, and the construction of a 12-membered lactone through an intramolecular Nozaki−Hiyama−Kishi coupling reaction.