Cyclization of farnesyl diphosphate to pentalenene. Orthogonal stereochemistry in an enzyme-catalyzed S(E') reaction

Article abstract of DOI:10.1139/v94-019

Pentalenene synthase catalyzes the cyclization of farnesyl diphosphate to (1) the sesquiterpene hydrocarbon pentalenene (4). Separate incubations of (4S,8S)-[4,8-³H₂, 4,8-¹⁴C₂]farnesyl diphosphate and (4R,8R)-[4,8-³H₂, 4,8¹⁴C₂]farnesyl diphosphate 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.