SYNTHESIS OF LINOLEIC-ACID WITH CHIRAL ISOTOPIC LABELING AT A FLANKING AND A MEDIAL ALLYLIC METHYLENE - THE (8R,9Z,12Z)-[8-H-2] AND (11R,9Z,12Z)-[11-H-2]-STEREOISOMERS, AND (Z)-[2,2-(H-2)2]NON-3-ENAL

[1-H-2]Oct-2-ynal is converted by fermenting bakers' yeast into (1S)-[1-H-2]oct-2-yn-l-ol with an enantiomeric purity of > 96% as measured by Mosher's MTPA method. The alcohol, as its tosyl ester, was then converted by copper-catalysed coupling with the di-Grignard of dec-9-ynoic acid and catalytic semi-hydrogenation, into (11R)-[11-H-2]linoleic acid having less than 2% E-material and >95 atom %D. Provision for (11S)-[11-H-2]linoleic acid was made by configurational inversion of (1R) - [1-H-2]oct-2-yn-1-ol using Mitsunobu chemistry. (8R)-[8-H-2]Linoleic acid is made by a similar approach, the labelled chiral centre being formed on (8S)-8-hydroxy-[8-H-2]octanoic acid (> 96% ee). Reaction of the corresponding tosate with lithium acetylide-ethylenediamine complex gave, with configurational inversion, (8R)-[8-H-2]dec-9-ynoic acid, built into (8R)-[8-H-2]linoleic acid. A degradative circuit is applied to estimate the extent of configurational inversion in the displacement. Mitsunobu inversion of the (8S)-8-hydroxy compound provides access to (8S)-[8-H-2]linoleic acid. (Z)-Non-3-enal, a labile aldehyde from the enzymic degradation of linoleic acid, is made in [2,2-H-2(2)]-labelled form by a synthesis which uses, as a key step, the reaction between triheptynylborane and deuteriodiazoacetic ester.