RING-A MODIFICATIONS OF PODOCARPIC ACID - TOWARDS THE SYNTHESIS OF QUASSINOIDS

Efficient methods for the formation of the hydroxy enone moieties in (17), (18), (45) and (46) from podocarpic acid (1) have been developed. The exocyclic alkene (13) has been converted into the alpha-hydroxy enones (17) and (18) in six steps and high overall yield. Oxidation of the enones (7) and (44) with manganese(III) acetate gave high yields of the alpha-acetoxy enones (10) and (47) and (48), respectively. Hydrolysis of (10), (47) and (48) afforded the alpha-hydroxy enones (11), (45) and (46), respectively. Hydroboration-oxidation of the alkene mixture (38) and (41) provided the alcohol (53) (53%) which was readily oxidized to the ketone (21) (92%). This ketone (21) was converted in three steps into the hydroxy enone (57) in 39% overall yield. Hydroxylation of the enone (44) via the silyl dienol ether (58) gave the alpha-hydroxy enones (45) (16%) and (46) (33%). The stereochemistry of 12-methoxy-19-nor-5-beta-podocarpa-3,8,11,13-tetraen-2-one (44) was estabilished by X-ray crystallography.