CYCLIZATION OF FARNESYL DIPHOSPHATE TO PENTALENENE - ORTHOGONAL STEREOCHEMISTRY IN AN ENZYME-CATALYZED S-E' REACTION

Pentalenene synthase catalyzes the cyclization of farnesyl diphosphate (1) to the sesquiterpene hydrocarbon pentalenene (4). Separate incubations of (4S,8S)-[4,8-H-3(2), 4,8-C-14(2)]farnesyl diphosphate (1a) and (4R,8R)-[4,8-H-3(2), 4,8(14)C(2)]farnesyl diphosphate (1b) with pentalenene synthase isolated from Streptomyces UC5319 and analysis of the derived labeled pentalenenes, 4a and 4b, respectively, by chemical degradation established that H-8si of FPP was lost upon cyclization to pentalenene. Consideration of the plausible conformations of the enzymatic cyclization intermediates indicates that the electrophilic allylic addition-elimination (S-E') reaction in which the C-4,5 bond of pentalenene is formed involves an orthogonal relationship between the C-C bond being formed and the C-H bond that is ultimately broken.