Synthesis and Antifungal Activity of Novel 14-Membered Benzomacrolides as Galbonolide Analogues.

Asymmetric total synthesis of benzene analogues of galbonolide, a 14-membered antifungal macrolide, possessing a benzene ring instead of a conjugated diene structure, was achieved starting from chiral 1-aryl-1-propanol obtained by enzyme-catalyzed kinetic resolution with high enantioselectivity. Representatively, a method for the introduction of a methylthio and chloride function at the vinyl position was also established. The resulting analogues unfortunately exhibited very little antifungal potency in comparison with galbonolide A.