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)-[9-2H1]-, (S)-[9-2H1]-, (R)-[10-2H1]-, (S)-[10-2H1]-, [9,9-2H2]-, and [10,10-2H2]-tridecanoic acids required as probes for biochemical studies on desaturases. The key intermediates in the synthesis of all these probes are ketones 9, which give rise to the corresponding alcohols 10 and 13 by reduction with LiAlD4 and LiAlH4, respectively. Derivatization of nondeuterated racemic alcohols 13 with (S)-(+)-9-anthranylmethoxyacetic acid ((S)-(+)-9-AMA) and chromatographic resolution of both diastereoisomers allowed us to determine the absolute configuration of the stereogenic centers by 1H NMR using an adaptation of the model proposed by Riguera and co-workers which was validated with alcohols of known absolute configuration. Both enantiomeric alcohols (R)- and (S)-13 were recovered by reduction of each diastereomeric ester with LiAlH4. Mesylation of alcohols 10 and 13 followed by nucleophilic substitution by LiAlD4 generated the saturated methoxymethyl derivatives 12 and 16, respectively. Final deprotection and Jones oxidation of the resulting alcohols afforded the above deuterated tridecanoic acids.