TOTAL SYNTHESIS OF SARCOPHYTOL-A, AN ANTICARCINOGENIC MARINE CEMBRANOID

A highly stereo- and enantioselective total synthesis of sarcophytol A (1), a marine cembranoid promising as a cancer chemopreventive agent, is described. The nitrile 10 obtained Z-selectively (Z:E = >35:1) by the Horner-Emmons reaction of (E,E)-farnesal (5) with the phosphononit rile 9 in 91% yield was converted to the conjugated 2(Z),4(E)-dienal 3 in which the terminal (E)-methyl group was functionalized. Intramolec ular alkylation of the cyanohydrin TMS ether of 3 provided the macrocy clic ketone 2 in 79% of overall yield from 3 without isolation of the cyclic cyanohydrin 20 as well as its TMS ether 19. Reduction of 2 with several chiral LiAlH4 reagents afforded 1 highly enantioselectively ( 87-93% ee) in 78-97% yield, from which enantiomerically pure 1 (>99% e e) was readily obtained upon a single recrystallization.