Asymmetric synthesis of the stereoisomers of 11,12,15(S)-trihydroxyeicosa-5(Z),8(Z),13(E)-trienoic acid, a potent endothelium-derived vasodilator

The four stereoisomers of the endothelial-derived vasorelaxant 11,12,15(S)-trihydroxyeicosatrienoic acid [1, 11,12,15(S)THETA] were prepared by a triply convergent, asymmetric route that exploited the stereospecific, copper mediated cross-coupling of alpha,beta-dialkoxystannanes with organic electrophiles and the utility of dialkylthionocarbarnates as orthogonal alcohol protective groups. Only 11(R),12(S),15(S)-THETA was comparable to natural material by HPLC, GC/MS, and in vitro bioassay. (C) 2004 Elsevier Ltd. All rights reserved.