Stereochemistry of the cyclization-rearrangement of (+)-copalyl diphosphate to (-)-abietadiene catalyzed by recombinant abietadiene synthase from Abies grandis

[GRAPHICS] Syntheses and enzymatic cyclizations of 8 alpha-hydroxy-17-nor copalyl diph osphate (8a), (15R)-[15-H-2(1)] 8b, and (15R,17E) [15-H-3(1),17-H-2(1)] cop alyl diphosphate ([H-2,H-3] 2) catalyzed by recombinant abietadiene synthas e (rAS) gave 17-nor manoyl oxide (9a), (16E)-[16-H-2(1)] 9b, and (15S,16R)- [16-H-2(1),16-H-3(1)] abietadiene ([H-2(1),H-3(1)] 4), respectively. These and other results indicate that conversion of CPP (2) to abietadiene (4) o ccurs by anti S-N' cyclization to a sandaracopimar-15-en-8-yl carbocation i ntermediate (13(+), 13 beta-methyl) followed by hydrogen transfer and methy l migration: suprafacially on the si face of the vinyl group.