Preparation of methyl cis-9-, trans-11- and trans-9-, trans-11-octadecadienoate-17,17,18,18-d(4), two of the isomers of conjugated linoleic acid

A multi-step synthesis was used to prepare the cis-9, trans-11- and trans-9, trans-11-isomers (in a ratio of 46/54) of conjugated linoleic acid (cis-9, trans-11-octadecadienoic acid) labeled with deuterium atoms on the 17- and 18-carbon atoms (17,17,18,18-d(4)). The methyl cis/trans-9, trans-11-octadecadienoate-17,17,18,18-d(4) isomer pair were obtained from the Wittig coupling of trans-2-nonenyltriphenyl-phosphonium bromide (8,8,9,9-d(4)) and methyl 9-oxononanoate. To prepare the phosphonium bromide, 5-hexyn-1-ol was reduced with deuterium gas/Wilkinson's catalyst to yield 1-hexanol-5,5,6,6-d(4). The alcohol was converted to the iodide with phosphorous pentoxide/phosphoric acid/potassium iodide. Coupling of the iodide with 2-propyn-1-ol via lithium amide in liquid ammonia gave 2-nonyn-1-ol-d(4). The acetylenic alcohol was reduced with lithium metal in liquid ammonia to yield the trans-2-nonen-1-ol-d(4). The alcohol was converted to the bromide (using triphenylphosphine dibromide) and then converted to the phosphonium salt. The aldehyde ester was prepared by the reductive ozonization of methyl 9-cis-octadecenoate. The two conjugated linoleic acid isomers, formed during the final Wittig coupling reaction, were readily separated by a combination of reversed-phase and silver resin chromatography. Isotopic and chemical purities were > 95% for each geometric isomer. Overall yield (both isomers) from the 8-step synthesis was 12%. (C) 1997 Elsevier Science Ireland Ltd.