15 新奇鎮痛活性物質Incarvillateineの全合成(口頭発表の部)

抄録

The first total synthesis of a novel potent antinociceptive monoterpene alkaloid incarvillateine (1) and its congenetic alkaloids incarvine C (2) and incarvilline (3) is presented. The synthetic plan for incarvillateine (1) we conceived relied on [2π+2π] cycloaddition of incarvine C (2). Thus, the synthesis of 2 started with (S)-4-siloxycyclopentenone 12, prepared from L-tartaric acid, upon treatment of 12 with the organozinc reagent generated in situ from (E)-stannylalkene 14, followed by addition of iodomethane, affording the 2,3,4-trisubstituted cyclopentane 15 as a single stereoisomer. The cyclopentenone 20 derived from 15 in five steps was then cyclized to the octahydrocyclopenta[c]pyridine 21 by means of the reductive Heck reaction using palladium(II) catalyst in the presence of formic acid. Compound 21 was stereoselectively converted to 6-epi-incarvilline (4) via reduction of the C-6 carbonyl group and catalytic hydrogenation of exocyclic alkene. Mitsunobu inversion of the C-6 hydroxy configuration of 4 led to the synthesis of (-)-incarvilline (3). On the other hand, Mitsunobu condensation of 4 with ferulic acid resulted in the synthesis of (+)-incarvine C (2). Attempted photodimerization of 2, however, failed to yield the expected [2+2] cycloadduct. The total synthesis of (-)-incarvillateine (1) was successsfully achieved by Mitsunobu condensation of 4 with the α-truxillic acid, prepared by head-to-tail photodimerization of the O- tosyl derivative of ferulic acid.