Wittig Cyclization of ω-Hydroxy Hemiacetals: Synthesis of (+)-Aspicilin.

The polyhydroxylated 18-membered lichen macrolide (+)-aspicilin was synthesized in 12 steps and 17% yield (longest linear sequence) starting from d-mannose and (S)-propylene oxide as the source of the stereogenic centers. Key steps were a palladium-catalyzed CX-CZnX Negishi cross-coupling affording an ω-hydroxy hemiacetal which was macrocyclized via a domino addition-Wittig olefination reaction with the cumulated ylide PhPCCO. This synthetic approach also allowed a regioselective glycosylation of 6-OH of aspicilin with d-desosamine, a quick entry to chimeric macrolides with potential antibiotic activity.