Synthesis of four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide via the asymmetric transformation (combined isomerization-preferential crystallization) of 1,4-thiazane-3-carboxylic acid

In order to synthesize four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide (TCA . SO), (S)-1,4-thiazane-3-carboxylic acid [(S)-TCA], which is one of the precursors, was prepared by the asymmetric trans-formation (com bined isomerization-preferential crystallization) of (RS)-TCA. This asymmet ric transformation was used (2R, 3R)-tartaric acid [(R)-TA] as a resolving agent and salicylaldehyde as the epimerization catalyst in propanoic acid a t 110 degrees C to afford a salt of (S)-TCA with (R)-TA in 100% de with a y ield of over 90%. Optically pure (S)-TCA was obtained by treating the salt with triethylamine in methanol in a yield of over 80%, based on (RS)-TCA as the starting material. In addition, asymmetric transformation of (R)-TCA g ave (S)-TCA in a yield of 60-70%. (S)-TCA was oxidized by hydrogen peroxide in dilute hydrochloric acid to selectively crystallize (1S,3S)-TCA . SO. ( 1R,3S)-TCA . SO of 70% de from the filtrate was allowed to form a salt with (R)-TA after a treatment with triethylamine to give (1R, 3S)-TCA . SO as a single diastereoisomer. (1R, 3R)- and (1S, 3R)-TCA . SO were also prepared by starting from (R)-TCA that had been synthesized from L-cysteine.