5583-33-5Relevant articles and documents
Electronic Effect-Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols
Li, Dan-Yang,Lou, Yu-Jiao,Xu, Jian,Chen, Xiao-Yang,Lin, Xian-Fu,Wu, Qi
, p. 1867 - 1872 (2021/02/12)
Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl)methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of S-enantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values. (Figure presented.).
Asymmetric reduction of aromatic heterocyclic ketones with bio-based catalyst Lactobacillus kefiri P2
Bayda?, Yasemin,Kalay, Erbay,?ahin, Engin
, p. 1147 - 1155 (2020/10/06)
Abstract: Chiral heterocyclic secondary alcohols have received much attention due to their widespread use in pharmaceutical intermediates. In this study, Lactobacillus kefiri P2 biocatalysts isolated from traditional dairy products, were used to catalyze the asymmetric reduction of prochiral ketones to chiral secondary alcohols. Secondary chiral carbinols were obtained by asymmetric bioreduction of different prochiral substrates with results up to > 99% enantiomeric excess (ee). (R)-1-(benzofuran-2-yl)ethanol 5a, which can be used in the synthesis of pharmaceuticals such as bufuralols potent nonselective β-blockers antagonists, Amiodarone (cardiac anti-arrhythmic), and Benziodarone (coronary vasodilator), was produced in gram-scale, high yield and enantiomerically pure form using L. kefiri P2 biocatalysts. The gram-scale production was carried out, and 9.70?g of (R)-5a in enantiomerically pure form was obtained in 96% yield. Also, production of (R)-5a in terms of yield and gram scale through catalytic asymmetric reduction using the biocatalyst was the highest report so far. This is a cost-effective, clean and eco-friendly process for the preparation of chiral secondary alcohols compared to chemical processes. From an environmental and economic perspective, this biocatalytic method has great application potential, making it a green and sustainable way of synthesis. Graphical Abstract: [Figure not available: see fulltext.]
Molecular switch manipulating Prelog priority of an alcohol dehydrogenase toward bulky-bulky ketones
Xu, Guochao,Dai, Wei,Wang, Yue,Zhang, Lu,Sun, Zewen,Zhou, Jieyu,Ni, Ye
, (2019/12/27)
Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237 G toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4’-chlorophenyl)-phenylmethanone, (4’-bromophenyl)-phenylmethanone and (4’-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.
