Total Synthesis of Sarcophytol A, an Anticarcinogenic Marine Cembranoid

Article abstract of DOI:10.1021/jo00089a011

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 phosphononitrile 9 in 91percent yield was converted to the conjugated 2(Z),4(E)-dienal 3 in which the terminal (E)-methyl group was functionalized.Intramolecular alkylation of the cyanohydrin TMS ether of 3 provided the macrocyclic ketone 2 in 79percent 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 (87-93percent ee) in 78-97percent yield from which enantiomerically pure 1 (>99percent ee) was readily obtained upon a single recrystallization.