title: Synthesis of (6Z,9Z,11E)-octadecatrienoic and (8Z,11Z,13E)-eicosatrienoic acids and their [1-(14)C]-radiolabeled analogs.
abstract: In order to study the metabolic pathway and the physiological effects of 9c,11t-18:2 (major isomer of conjugated linoleic acid) and its C(18:3) and C(20:3) metabolites, 6c,9c,11t-18:3 and 8c,11c,13t-20:3 and their [1-(14)C]-radiolabeled analogs were prepared stereoselectively by total synthesis. The 8c,11c,13t-20:3 was obtained in 11 steps. The synthesis involves a highly stereoselective Wittig reaction between 3-(t-butyldiphenylsilyloxy)propanal and the ylide of 7-(2-tetrahydropyranyloxy)heptanylphosphonium salt which gave (3Z)-1-(t-butyldiphenylsilyloxy)-10-(2-tetrahydropyranyloxy)dec-3-ene in a first step. Then the t-butyldiphenylsilyl derivative was deprotected selectively and the resulting alcohol function was converted via a bromide into a phosphonium salt. The second stereoselective Wittig condensation between the phosphonium salt and commercial (2E)-non-2-enal under cis-olefinic conditions using Lithium hexamethyldisilazide as base afforded the (7Z,10Z,12E)-1-(2-tetrahydropyranyloxy)nonadeca-7,10,12-triene in a very good isomeric purity. The intermediate product was brominated and transformed by reaction with magnesium into Grignard reagent, which was one-carbon elongated by unlabeled or labeled carbon dioxide to obtain the 8c,11c,13t-20:3 in good isomeric purity (95%) and high radiochemical purity for its [1-(14)C]-radiolabeled analog (99%). 6c,9c,11t-18:3 was synthesized in a similar way by using 5-(2-tetrahydropyranyloxy)pentanylphosphonium salt in place of 7-(2-tetrahydropyranyloxy)heptanylphosphonium salt in a first step. Other reactions were unchanged and products were obtained in similar yields. Similar to 8c,11c,13t-20:3, the 6c,9c,11t-18:3 was obtained in a very good isomeric purity (95%) and its [1-(14)C]-radiolabeled analog in a high radiochemical purity (95%).
authors.affiliation: Unité de Nutrition Lipidique, Institut National de la Recherche Agronomique (INRA), 17 rue Sully, BP 86510, F-21065 Dijon Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Gnädig
authors.forename: O
authors.initials: O
authors.lastname: Berdeaux
authors.forename: O
authors.initials: O
authors.lastname: Loreau
authors.forename: J P
authors.initials: JP
authors.lastname: Noël
authors.forename: J L
authors.initials: JL
authors.lastname: Sébédio
mesh_terms: D016588:Anticarcinogenic Agents / Q000138:chemical synthesis; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis*; D006880:Hydroxy Acids / Q000138:chemical synthesis*
chemical_list: C438961:(6Z,9Z,11E)-octadecatrienoic acid; C438962:(8Z,11Z,13E)-eicosatrienoic acid; D016588:Anticarcinogenic Agents; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids