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- MakaleYalnız künye2023Scopus SJRQ3Modified distance optimization method for the asymmetric bioreduction conditions of phenyl(thiophen-2-yl)methanone by Weissella paramesenteroides N7
Özdemir, Akın; Şahin, Engin
Chirality plays a significant part in life since it is closely linked to carrying out the many metabolic processes that make up a living being. Chiral secondary alcohols such as diaryl-, aryl heteroaryl-, and diheteroaryl are employed in pharmaceuticals as drug intermediates. Although biocatalytic asymmetric reduction of prochiral ketones containing aromatic and heteroaromatic groups is widely known, biocatalytic reduction of heteroaromatic prochiral ketones containing sulfur heteroatoms is rarely known. Very few studies exist in the literature, including the biocatalytic reduction of phenyl(thiophen-2-yl)methanone (1). Moreover, the biocatalytic reduction of 1 with a mathematical modelling and optimization technique is unknown until now. In this study, Weissella paramesenteroides N7 biocatalyst for the asymmetric bioreduction of 1 using a novel modified distance optimization method. Optimization conditions were found as pH = 6.46, temperature = 26 °C, incubation period = 71 h, agitation speed = 200 rpm by the modified distance optimization method, and it was determined that the conversion and enantiomeric excess (ee) under these conditions could be 98.7% and 98%, respectively. Under these proposed optimization conditions, (S)-phenyl(thiophen-2-yl)methanol ((S)-2) was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 11.29 g of 1 was completely converted into (S)-2 (11.07 g, 97% isolated yield) under optimized conditions. This is the first report about the fabrication of enantiopure (S)-2 in high gram scale using a biocatalyst and a novel modified distance optimization technique. In this study, the successful applicability of the new modified distance optimization method in biocatalytic asymmetric reduction reactions has been successfully demonstrated.
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İncele - MakaleAçık Erişim2022Scopus SJRQ3Production of enantiomerically enriched chiral carbinols using whole-cell biocatalyst
Baydaş, Yasemin; Kalay, Erbay; Şahin, Engin
Biocatalytic asymmetric reduction of ketone is an efficient method for the production of chiral carbinols. The study indicates selective bioreduction of different ketones (1–8) to their respective (R)-alcohols (1a–8a) in low to high selectivity (0- >99%) with good yields (11–96%). In this work, whole-cell of Lactobacillus kefiri P2 catalysed enantioselective reduction of various prochiral ketones was investigated. (R)-4-Phenyl-2-butanol 2a, which is used as a precursor to antihypertensive agents and spasmolytics (anti-epileptic agents), was obtained using L kefiri P2 in 99% conversion and 91% enantiomeric excess (ee). Moreover, bioreduction of 2-methyl-1-phenylpropan-1-one substrate 8, containing a branched alkyl chain and difficult to asymmetric reduction with chemical catalysts as an enantioselective, to (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was carried out in excellent yield (96%). The gram-scale production was carried out, and 9.70 g of (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was obtained in 96% yield. Also especially, the yield and gram scale of (R)-2-methyl-1-phenylpropan-1-ol (8a) synthesised through catalytic asymmetric reduction using the biocatalyst was the highest report so far. The efficiency of L kefiri P2 for the conversion of the substrates and ee of products were markedly influenced by the steric factors of the substrates. This is a cheap, clean and eco-friendly process for production of chiral carbinols compared to chemical processes.
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