Syntheses of geometric isomers of di-, tetra-, and hexadeuterated 12-octadecenoates and their triglycerides

Four geometrically isomeric deuterated 12‐octadecenoates and their triglycerides were synthesized for use in metabolism studies in humans. Methyl trans‐12‐octadecenoate‐15,15,16,16‐d4 (81.7% d4) and the corresponding cis isomer (88.9% d4) were obtained by the Wittig reaction between hexyl‐3,3,4,4‐d4‐triphenylphosphonium bromide (or iodide) and methyl 12‐oxododecanoate. The phosphonium salt was derived, in several steps, from 3‐hexynol and the methyl 12‐oxododecanoate from cyclododecene. Methyl cis‐12‐octadecenoate‐9,10,15,15,16,16‐d6 (79.9% d6) was obtained via the Wittig reaction between hexyl‐d4‐triphenylphosphonium bromide and methyl 12‐oxododecanoate‐9,10‐d2. This deuterated aldehyde ester was prepared by lead tetraacetate oxidation of methyl 12,13‐dihydroxyoctadecanoate‐9,10‐d2 which was obtained, in several steps, from Vernonia anthelmintica seed oil. A simple and convenient stereospecific synthesis of methyl trans‐12‐octadecenoate‐9,10‐d2 (84.9% d2) was accomplished by thermal decomposition of methyl 12,13‐di‐O‐(ethoxymethylene)‐octadecanoate‐9,10‐d2 which was prepared, in several steps, from 12,13‐epoxy‐9‐octadecenoate obtained from Vernonia oil. All deuterations were catalyzed by tris(triphenylphosphine)chlororhodium. cis‐ and trans‐ isomers were separated on an Amberlyst XN 1005 column impregnated with silver ions.