Efficient synthesis of de-O-methyllasiodiplodin

Resorcinolic macrolides are a large class of fungal natural products with conserved resorcinolic ester cores within highly variable ten- to fourteen-membered macrocycles. They exhibit a broad range of biological activities, depending largely on the size and substitution on the macrocyclic bridge. Here we report a protecting group-free synthesis of de-O-methyllasiodiplodin, a minimal resorcinolic macrolide derived from the fungus Lasiodiplodia theobromae. The route proceeds 42% yield over 5 steps (longest linear sequence) from 9-decenoic acid, a cheap and abundant starting material. Given the broad commercial availability of a variety of similar (terminal)-enoic acids, this route provides an entry to libraries of resorcinolic macrolides with highly variable macrocyclic bridges.