SYNTHETIC STUDIES ON APHIDICOLANE AND STEMODANE DITERPENES .4. A STEREOSELECTIVE FORMAL TOTAL SYNTHESIS OF (+/-)-APHIDICOLIN

A formal total synthesis of (+/-)-aphidicolin (1) was accomplished starting from the tricyclic ketone (2) corresponding to the B/C/D ring system. The quaternary carbon center adjacent to the spirocarbon was constructed stereoselectively by conjugate addition of a methyl group to the enone (7) obtained from 2 in a four-step sequence, The tetracyclic enone (3) was obtained via acid-catalyzed intramolecular aldol condensation of the tricarbonyl compound (10) followed by 1,3-carbonyl transposition, in which Pd(0)-catalyzed reductive deacetoxylation of gamma-acetoxy-alpha,beta-enone (15) was a crucial step. The A-ring manipulation was performed by a similar procedure to the Ireland method to give the keto-acetonide (4), a degradation product of 1, which has already been efficiently reconverted to 1.