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

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.