Baker’s yeast catalyzed preparation of a new enantiomerically pure synthon of (S)-pramipexole and its enantiomer (dexpramipexole)

A biocatalyzed reduction of a prochiral bicyclic ketone afforded enantiomerically pure (R)-2-acetylamino-6-hydroxy-4,5,6,7-tetrahydrobenzothiazole, a synthon of the anti-Parkinson (S)-pramipexole and its (R)-isomer, which is currently under investigation for the treatment of amyotrophic lateral sclerosis (ALS).

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(R)-2-Acetylamino-6-hydroxy-4,5,6,7-tetrahydrobenzothiazoleC9H12N2O2S>98% ee (by HPLC)[α]D20 = +25.5 (c 1 CH3OH)Source of chirality: Saccharomyces cerevisiaeAbsolute configuration: (R)

(S)-2-Acetylamino-6-amino-4,5,6,7-tetrahydrobenzothiazoleC9H13N3OS>98% ee (by HPLC)[α]D20 = −59.1 (c 1 CH3OH)Source of chirality: Saccharomyces cerevisiaeAbsolute configuration: (S)

(S)-2,6-Diamino-4,5,6,7-tetrahydrobenzothiazoleC7H11N3S>98% ee (by HPLC)[α]D20 = −91.0 (c 1 CH3OH)Source of chirality: Saccharomyces cerevisiaeAbsolute configuration: (S)