Pd触媒を用いるジヒドロピラン環形成反応と(–)-laulimalide合成

抄録

(–)-Laulimalide is a potent cell growth inhibitor with low nanomolar IC50 values that was isolated from Cacospongia mycofijiensis, Hyattella sp. and Fasciospongia rimosa. Laulimalide stimulates tubulin polymerization by a mechanism similar to that of paclitaxel, but unlike paclitaxel, inhibits proliferation of SKVLB-1, a multidrug-resistant cell line. The structure of laulimalide has two substituted dihydropyran rings inside and outside of the 20 membered macro lactone ring. These two specific dihydropyran rings have been constructed by Pd⁰ and Pd^II catalyzed ring formation reaction of allyl carbonate and allyl alcohol stereospecifically. Two fragments having allylsilane unit and unsaturated aldehyde unit have been assembled by Sakurai–Hosomi reaction and additional 5 steps have afforded the seco-acid, which was reported as a precursor of (–)-laulimalide.

Scheme 1