Synthesis of dideuterated and enantiomers of monodeuterated tridecanoic acids at C-9 and C-10 positions

We report a route for the preparation of mono and dideuterated tridecanoic acids: (R)-[9-H-2(1)]-, (S)-[9-H-2(1)]-, (R)-[10-H-2(1)]-, (S)-[10-H-2(1)]- , [9,9-H-2(2)]-, and [10,10-H-2(2)]-tridecanoic acids required as probes fo r biochemical studies on desaturases. The key intermediates in the synthesi s of all these probes are ketones 9, which give rise to the corresponding a lcohols 10 and 13 by reduction with LiAlD4 and LiAlH4, respectively. Deriva tization of nondeuterated racemic alcohols 13 with (S)-(+)-9-anthranylmetho xyacetic acid ((S)-(+)-9-AMA) and chromatographic resolution of both diaste reoisomers allowed us to determine the absolute configuration of the stereo genic centers by H-1 NMR using an adaptation of the model proposed by Rigue ra and co-workers which was validated with alcohols of known absolute confi guration. Bath enantiomeric alcohols (R)- and (S)-13 were recovered by redu ction of each diastereomeric ester with LiAlHa(4). Mesylation of alcohols 1 0 and 13 followed by nucleophilic substitution by LiAlD4 generated the satu rated methoxymethyl derivatives 12 and 16, respectively. Final deprotection and Jones oxidation of the resulting alcohols afforded the above deuterate d tridecanoic acids.