Transannular Proton Transfer in the Cyclization of Geranylgeranyl Diphosphate to Fusicoccadiene, a Biosynthetic Intermediate of Fusicoccins

Abstract

Enzymatic cyclization of geranylgeranyl diphosphate to fusicoccadiene involves a transannular proton transfer process. Label distribution in the cyclized products derived from deuterium-labeled GGDPs showed that a proton generated from C-10 migrates to C-6 in the intermediary dolabellane framework prior to the second ring formation. Although a direct 1,5-proton transfer would achieve this process, semiempirical MO calculations suggested an alternative pathway, which involves successive 1,4- and 1,5-proton transfers using C-2 as a springboard.