Total Synthesis of Crotophorbolone.
The complex ABC-tricyclic structure of crotophorbolone, a derivative of the tigliane diterpenoids, was assembled by coupling of simple fragments. The six-membered C-ring fragment, having five contiguous stereocenters, was stereoselectively constructed from (R)-carvone. After attachment of the five-membered A-ring through the π-allyl Stille coupling reaction, the α-alkoxy bridgehead radical reaction effected the endo-cyclization of the seven-membered B-ring by forming the sterically congested bond at C9 and C10 stereospecifically and stereoselectively, respectively. Finally, the functional groups on the 5/7/6-membered ring system were manipulated by rhodium-catalyzed C2 olefin isomerization, C13 decarboxylative oxidation, and C4 hydroxylation, thus completing the first total synthesis of crotophorbolone.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Taro
T
Asaba
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Yuki
Y
Katoh
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Daisuke
D
Urabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan). inoue@mol.f.u-tokyo.ac.jp.
Masayuki
M
Inoue
cross-coupling; natural products; radical reactions; terpenoids; total synthesis