ENANTIOSPECIFIC AND STEREOSPECIFIC SYNTHESIS OF LIPOXIN-A - STEREOCHEMICAL ASSIGNMENT OF THE NATURAL LIPOXIN-A AND ITS POSSIBLE BIOSYNTHESIS

Both chemical and enzymatic steps were employed to convert leukotriene A4 and its unnatural epoxide isomers into 4 diastereomeric 5(S),6(S),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acids, possible structures for lipoxin A. These compounds were correlated with trihydroxy, tetraene eicosatetraenoic acids derived from tetraene epoxide 3, and the relative stereochemistries of the 5 and 6 positions were assigned. These assignments were confirmed by total synthesis of 2 diastereomers of lipoxin A. One of these isomers, 5(S),6(S),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid, corresponded to lipoxin A derived from natural sources. The structure and possible biosyntheses of lipoxin A are proposed.