A single-step synthesis of (R)-α-methyl- 4-pyridinemethanol from (RS)-α-methyl-4- pyridinemethanol by stereoinversion using whole cells of Candida parapsilosis is reported. Among the various strains of Candida species examined, C. parapsilosis demonstrated to have the best oxidoreductase system for stereoinversion of (RS)-α-methyl-4-pyridinemethanol. The effect of various physicochemical parameters on the stereoinversion process, were studied. Under optimized conditions approximately 97% enantiomeric excess of (R)-α-methyl-4-pyridinemethanol (eeR) was obtained with 99% yield was obtained. The optimized parameters were determined to be a substrate concentration of 5 mM, pH 8.0, 30°C incubation temperature, and a reaction time of 48 h. The reactions were also carried out in different organic solvents, and maximum stereoinversion was obtained in 1,4-dioxane with 78.4% eeR and 74.7% yield, which are lower than those in phosphate buffer. This whole cell catalysis for the preparation of (R)-α-methyl-4- pyridinemethanol is an example of a green, enantiopure synthesis of secondary alcohols.
The present study describes an efficient chemoenzymatic synthesis of enantiopure (S)-Practolol, a selective β-adrenergic receptor blocker. Prior to the synthesis of the target, a synthetic protocol for (RS)-N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide, an essential precursor, was developed. Various commercial lipases were screened for the kinetic resolution of (RS)- N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide using toluene as solvent and vinyl acetate as an acyl donor. Among various lipases screened, Pseudomonas cepacia sol-gel AK showed the highest enantioselectivity (96% enantiomeric excess with 50% conversion), affording (S)-1-(4-acetamidophenoxy)-3-chloropropan-2-yl acetate. Optimization of the reaction parameters was carried out in order to find the best-suited conditions for the biocatalysis. Furthermore, the enantiopure intermediate was hydrolyzed and the resulting product was reacted with isopropylamine to afford (S)-Practolol. This biocatalytic procedure depicts a green technology for the synthesis of (S)-Practolol with better yield and enantiomeric excess.
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