Submitted to: Chemistry and Physics of Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/11/1997
Publication Date: N/A
Interpretive Summary: Conjugated linoleic acid is a group of fats which have been implicated in a variety of physiological and biochemical effects in humans, such as suppression of cancer, stimulation of the immune system and cardiovascular health. A method of preparing small quantities of two of these potentially valuable fats labelled with deuterium atoms was devised. The nutritive impact of these materials in humans is unknown. The deuterium tag, however, will allow researchers to safely study the metabolism and interaction of these fats in humans.
Technical Abstract: 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-d4). The methyl cis/ trans-9, trans-11 octadecadienoate-17,17,18,18-d4 isomer pair were obtained from the Wittig coupling of trans-2-nonenyltriphenyl-phosphonium bromide (8,8,9,9-d4) 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-d4. 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-d4. The acetylenic alcohol was reduced with lithium metal in liquid ammonia to yield the trans-2-nonen-1-ol-d4. 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%.