Synthesis of (9Z,12Z,15E)- and (9E,12Z,15Z)-octadecatrienoic acids and their [1-14C]-radiolabelled analogs (original) (raw)

1994, Chemistry and Physics of Lipids

In order to study the effect of the double bonds geometry of linolenic acid (18:3 n-3) on its biological activities, (gz,12Z, I 5E)-and (9E, I 2Z, 15Z)-octadecatrienoic acids, found in many refined vegetable oils, were made by total synthesis. Synthesis of 18:3 A9c, 12c, 1St involves a Wittig reaction between 3-(2-tetrahydropyranyloxy)-propylphosphonium salt and (E)-3-hexenal which gave (3Z,6E)-l-(2-tetrahydropyranyloxy)-nonadiene in 66% yield. The transformation of the ether function to a phosphonium salt, followed by a Wittig reaction with 8-(t-butyldimethylsilyloxy)-octanal afforded a C17 trienic ether. A one-carbon homologation of its corresponding bromide with potassium cyanide followed by hydrolysis in basic medium furnished 18:3 A9c, 12c, 15t in high isomeric purity and high radiochemical purity for its [l-J4C]-Iabelled analog. In the synthesis of 18:3 A9t, 12c, 15c, a Wittig reaction between (E)-6-(2-tetrahydropyranyloxy)-hex-3-enylphosphonium salt, obtained in three steps from 6-(2-tetrahydropyranyloxy)hex-3-yn-l-ol and (Z)-3-hexenal afforded a C12 (E,Z,Z)-trienic ether. After a six-carbon homologation of this ether, in three steps, the resulting nitrile was hydrolyzed to (9E,12Z,15Z)-octadecatrienoic acid (99% purity) (99% radiochemical purity of its [1-14C]-labelled analog).