Highly Stereoselective Total Synthesis of Methynolide, the Aglycon of the 12-Membered Macrolide Antibiotic Methymycin. I. Synthesis of a Prelog-Djerassi Lactone-Type Chiral Intermediate from D-Glucose

Abstract

For the highly stereoselective synthesis of methynolide (2), the aglycon of the 12-membered macrolide antibiotic methymycin (1), a Prelog-Djerassi lactone-type chiral intermediate (7a) bearing four chiral centers corresponding to the C-2, C-3, C-4, and C-6 positions was synthesized from D-glucose. In this synthesis, several stereocontrolled reactions such as hydroboration, catalytic hydrogenation, etc. were successfully applied. The utility of the 4-methoxybenzyl protecting group was also demonstrated.