39 Pseudoguaianolidesの合成研究 : (±)-Carpesiolinの全合成

抄録

A total synthesis of (±)-carpesiolin (1), an antibiotic substance, is described along a new, efficient and straightforward route to this class of sesquiterpenoides (pseudoguaianolides). This route features on the following three points: 1) the stereochemically defined introduction of C_<10> (pseudoguaianolide numbering) methyl group in a-orientation, 2) the regiospecific ring expansion reaction leading to the trans-perhydroazulenone skeleton, and 3) the complete stereo-control of other chiralities (C_6-C_8) on the 7-membered ring. The severe 1,3-diaxial interaction in the β-methyl ketone (4) caused a complete isomerization to its α-methyl isomer (3), which was ring-expanded regiospecifically to the perhydroazulenone (7). The ketone 7 was converted to the γ-lactone (16) in 5 steps, whose trifluoroacetate (17) on treatment with an acid was transformed into the alcohol (18) via an unexpected intramolecular acyl migration. The title compound 1 was synthesized in further 7 steps from 18. Application of this methodology to other pseudoguaianolides is in progress.