T. Tanaka et al., SYNTHETIC STUDIES ON APHIDICOLANE AND STEMODANE DITERPENES .4. A STEREOSELECTIVE FORMAL TOTAL SYNTHESIS OF (+ -)-APHIDICOLIN/, Chemical and Pharmaceutical Bulletin, 43(2), 1995, pp. 193-197
A formal total synthesis of (+/-)-aphidicolin (1) was accomplished sta
rting from the tricyclic ketone (2) corresponding to the B/C/D ring sy
stem. The quaternary carbon center adjacent to the spirocarbon was con
structed 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 conden
sation of the tricarbonyl compound (10) followed by 1,3-carbonyl trans
position, in which Pd(0)-catalyzed reductive deacetoxylation of gamma-
acetoxy-alpha,beta-enone (15) was a crucial step. The A-ring manipulat
ion 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.