Total Synthesis of Naturally Occurring Mycolic Acids. (E)- and (Z)-threo-2-Docosyl-3-hydroxytetracont-21-enoate

Article abstract of DOI:10.1021/jo00142a003

The ethyl esters of (E)- and (Z)-2-docosyl-3-hydroxytetracont-21-enoate (4a and 4b, respectively) have been prepared by a route involving alkylation of the dianion of ethyl 2-docosyl-3-oxobutyrate (2) with either (E)-1-iodo-17-hexatriacontene (14c) or (Z)-1-iodo-17-hexatriacontene (13c) and subsequent borohydride reduction of the intermediate β-keto esters (3a and 3b, respectively).Resolution of the 3:2 mixture of erythro and threo diastereomers of 4a and 4b was accomplished by high-performance liquid chromatography, employing phenacyl ester derivatives.The ¹H NMR spectra of phenacyl (E)-threo-2-docosyl-3-hydroxytetracont-21-enoate (6a) and phenacyl (Z)-threo-2-docosyl-3-hydroxytetracont-21-enoate (6b) were identical with the spectra previously reported for the phenacyl esters of the naturally occurring monoalkene mycolic acids from Mycobacterium smegmatis (see ref 10).An examination of the phenacyl ester of the epoxide derivative of the naturally occurring mycolic acid by ¹H NMR spectroscopy established that it was a 93:7 mixture of the Z and E isomers, respectively, of phenacyl threo-2-docosyl-3-hydroxytetracont-21-enoate.