Safety of Phenyl(pyridin-2-yl)methanone. Recently I am researching about CARBONYL REDUCTASE; INSIGHTS; PROLINE; MUTAGENESIS; CATALYSIS; DYNAMICS; PRELOG; POCKET; OXIDE; SHAPE, Saw an article supported by the National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773616]; Program of Shanghai Technology Research Leader [17XD1423200]; Seed Fund Program of the Shanghai University of Medicine & Health Sciences [SFP-18-22-07-002]. Published in ROYAL SOC CHEMISTRY in CAMBRIDGE ,Authors: Wu, K; Yang, ZJ; Meng, XG; Chen, R; Huang, JK; Shao, L. The CAS is 91-02-1. Through research, I have a further understanding and discovery of Phenyl(pyridin-2-yl)methanone
Steric hindrance in the binding pocket of an alcohol dehydrogenase (ADH) has a great impact on its activity and stereoselectivity simultaneously. Due to the subtle structural difference between two bulky phenyl substituents, the asymmetric synthesis of diaryl alcohols by bioreduction of diaryl ketones is often hindered by the low activity and stereoselectivity of ADHs. To engineer an ADH with practical properties and to investigate the molecular mechanism behind the asymmetric biocatalysis of diaryl ketones, we engineered an ADH from Lactobacillus kefiri (LkADH) to asymmetrically catalyse the reduction of 4-chlorodiphenylketones (CPPK), which are not catalysed by the wild type (WT) enzyme. Mutants seq1-seq5 with gradually increased activity and stereoselectivity were obtained through iterative shrinking mutagenesis. The final mutant seq5 (Y190P/I144V/L199V/E145C/M206F) demonstrated the highest activity and excellent stereoselectivity of >99% ee. Molecular simulation analyses revealed that mutations may enhance the activity by eliminating steric hindrance, inducing a more open binding loop and constructing more noncovalent interactions. The pro-R pose of CPPK with a halogen bond formed a pre-reaction conformation more easily than the pro-S pose, resulting in the high ee of (R)-CPPO in seq5. Moreover, different halogen bonds formed due to the different positions of chlorine substituents, resulting in opposite substrate binding orientation and stereoselectivity. Therefore, the stereoselectivity of seq5 was inverted toward ortho- rather than para-chlorine substituted ketones. These results indicate that the stereocontrol element of LkADH was changed to recognise diaryl ketones after steric hindrance was eliminated. This study provides novel insights into the role of steric hindrance and noncovalent bonds in the determination of the activity and stereoselectivity of enzymes, and presents an approach producing key intermediates of chiral drugs with practical potential.
Safety of Phenyl(pyridin-2-yl)methanone. Bye, fridends, I hope you can learn more about C12H9NO, If you have any questions, you can browse other blog as well. See you lster.
Reference:
Pyridine – Wikipedia,
,Pyridine | C5H5N – PubChem