Loreau O, Maret A, Chardigny J M, Sébédio J L, Noël J P
CEA/Saclay, Service des Molécules Marquées, Bât. 547, F-91191 Gif sur Yvette Cedex, France.
Chem Phys Lipids. 2001 Mar;110(1):57-67. doi: 10.1016/s0009-3084(00)00229-2.
Conjugated linoleic acid (CLA) isomers are present in human foods derived from milk or ruminant meat. To study their metabolism, (9Z,11E)-, (10E,12Z)- and (10Z,12Z)-[1-(14)C]-octadecadienoic acids with high radiochemical and isomeric purities (>98%) were prepared by stereoselective multi-step syntheses involving sequential substitution of 1,2-dichloro-ethene. In the case of the (9Z,11E) isomer, a first metal-catalyzed cross-coupling reaction between (E)-1,2-dichloro-ethene and 2-non-8-ynyloxy-tetrahydro-pyran, obtained from 7-bromo-heptan-1-ol, gave a conjugated chloroenyne. A second coupling reaction with hexylmagnesium bromide provided a heptadecenynyl derivative. Stereoselective reduction of the triple bond and bromination afforded (7E,9Z)-17-bromo-heptadeca-7,9-diene. Formation of the Grignard reagent and carbonation with 14CO(2) gave (9Z,11E)-[1-(14)C]-octadeca-9,11-dienoic acid (overall yield from 7-bromo-heptan-1-ol, 14.4%). (10E,12Z)- and (10Z,12Z)-[1-(14)C]-octadeca-10,12-dienoic acids were synthesized by the same methodology using 1-heptyne, 8-bromo-octan-1-ol and, respectively, (E)-1,2-dichloro-ethene and its (Z) isomer (overall yield from 8-bromo-octan-1-ol, 13.1% (10E,12Z); 17.2% (10Z,12Z)). Impurities (<2% if present) were identified as being (E,E) CLA isomers and were removed by RP-HPLC. Metabolism studies in animal are in progress.
共轭亚油酸（CLA）异构体存在于源自牛奶或反刍动物肉类的人类食物中。为研究它们的代谢情况，通过涉及1,2 - 二氯乙烯顺序取代的立体选择性多步合成制备了具有高放射化学纯度和异构体纯度（>98%）的(9Z,11E)-、(10E,12Z)-和(10Z,12Z)-[1-(14)C]-十八碳二烯酸。对于(9Z,11E)异构体，(E)-1,2 - 二氯乙烯与由7 - 溴 - 庚醇制得的2 - 壬 - 8 - 炔氧基 - 四氢 - 吡喃之间的首次金属催化交叉偶联反应得到一种共轭氯烯炔。与己基溴化镁的第二次偶联反应得到一种十七碳烯炔基衍生物。三键的立体选择性还原和溴化得到(7E,9Z)-17 - 溴 - 十七碳 - 7,9 - 二烯。格氏试剂的形成以及用14CO(2)进行羧化反应得到(9Z,11E)-[1-(14)C]-十八碳 - 9,11 - 二烯酸（以7 - 溴 - 庚醇计的总收率为14.4%）。(10E,12Z)-和(10Z,12Z)-[1-(14)C]-十八碳 - 10,12 - 二烯酸采用相同方法合成，分别使用1 - 庚炔、8 - 溴 - 辛醇以及(E)-1,2 - 二氯乙烯及其(Z)异构体（以8 - 溴 - 辛醇计的总收率，(10E,12Z)为13.1%；(10Z,12Z)为17.2%）。杂质（若存在则<2%）被鉴定为(E,E)CLA异构体，并通过反相高效液相色谱法（RP - HPLC）除去。动物体内的代谢研究正在进行中。
