Formal total synthesis of mandelalide A

Abstract

In this article the formal total synthesis of mandelalide A has been described in details. The highly convergent and flexible strategy developed for mandelalide A involved the construction of key building blocks ent-9 and 7, and their assembly to the target compound. For the synthesis and coupling of these building blocks, the Brown’s crotylation, Sharpless asymmetric dihydroxylation followed by in situ Williamson type etherification, modified Prins cyclization, Masamune-Roush olefination and Heck cyclization were employed, the latter being crucial for the highly stereoselective formation of the macrocycle of mandelalide A. Initially, Julia Kocienski olefination, ring-closing metathesis reaction were investigated for the synthesis of the aglycone of the proposed structure of the mandelalide A, and found to be unsuccessful. Highly convergent and flexible strategy has been developed for mandelalide A via coupling of two building blocks ent-9 and 7 through Masamune-Roush olefination followed by intramolecular Heck cyclization.