114446-57-0Relevant articles and documents
Development of an Enzymatic Process for the Synthesis of (S)-2-Chloro-1-(2,4-dichlorophenyl) Ethanol
Wei, Teng-Yun,Tang, Jia-Wei,Ni, Guo-Wei,Wang, Hong-Yi,Yi, Dong,Zhang, Fu-Li,Chen, Shao-Xin
, p. 1822 - 1828 (2019)
(S)-2-Chloro-1-(2,4-dichlorophenyl) ethanol (3) is a chiral intermediate in the synthesis of luliconazole ((R)-E-1). Here, we report a novel biopreparation of 3 by bioreduction of 2-chloro-1-(2,4-dichlorophenyl) ethanone (2) using recombinant Escherichia
Efficient biosynthesis of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol using a mutant short-chain dehydrogenase from Novosphingobium aromaticivorans
Li, Guifang,Que, Fandi,Tang, Yunping,Zhao, Qiaojun,Zhou, Shuyao,Zhou, Yafeng
, (2020)
(R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CPEO) is an important chiral intermediate for antifungal drug synthesis. (R)-CPEO can be produced from 2-chloro-1-(2, 4-dichlorophenyl) ethanone (CPE) via a mutant short-chain dehydrogenase/reductase from Novosphingobium aromaticivorans (NaSDR). The Vmax of a mutant NaSDR-G145A/I199L toward CPE (6.32 U mg?1) was greater than that of wild-type NaSDR (2.58 U mg?). The Km of mutant NaSDR-G145A/I199L toward CPE (0.23 mM) was less than that of wild-type NaSDR (0.38 mM), indicating that the substrate affinity of mutant NaSDR-G145A/I199L was the greater of the two. Docking simulations were used to illustrate the mechanisms of the increased enzyme activity of NaSDR-G145A/I199L; these showed that NaSDR-G145A/I199L presented a more effective docking posture than that of the wild-type enzyme. Further, NaSDR-G145A/I199L and glucose dehydrogenase (GDH) were used to transform 120 g/L CPE into (R)-CPEO. After 6 h, the conversion rate and enantiomeric excess values were 99% and 99.95%, respectively. The present study provides a practical method for high substrate loading of (R)-CPEO for industrial-scale applications.
Asymmetric transfer hydrogenation over Ru-TsDPEN catalysts supported on siliceous mesocellular foam
Huang, Xiaohua,Ying, Jackie Y.
, p. 1825 - 1827 (2007)
A siliceous mesocellular foam-immobilized Ru-TsDPEN complex exhibited excellent catalytic reactivity, enantioselectivity and reusability in the asymmetric transfer hydrogenation of an imine and ketones. The Royal Society of Chemistry.
Biocatalytic preparation of a key intermediate of antifungal drugs using an alcohol dehydrogenase with high organic tolerance
Yan, Jinrong,Wang, Xiaojing,Li, Fangling,Yang, Lei,Shi, Guixiang,Sun, Weihang,Shao, Lei,Huang, Junhai,Wu, Kai
supporting information, (2021/10/20)
In this study, an alcohol dehydrogenase derived from Lactobacillus kefir (LkADH) was engineered and a simple and practical bioreduction system was developed for the preparation of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CDPO), a key intermediate for the synthesis of antifungal drugs. Through active pocket iterative saturation mutagenesis, mutant LkADH-D18 (Y190C/V196L/M206H/D150H) was obtained with high stereoselectivity (99% ee, R vs 87% ee, S) and increased activity (0.44 μmol·min?1·mg?1). LkADH-D18 demonstrated NAD(P)H regeneration capability using a high concentration of isopropanol (IPA) as a co-substrate. Using 40% IPA (v/v), 400 mM of (R)-CDPO (90.1 g·L-1) was obtained via complete substrate conversion using 40 mg·mL?1 LkADH-D18 wet cells. The biocatalytic process catalyzed at constant pH with the cheap co-solvent IPA contributed to improved isolated yield of (R)-CDPO (97%), lower reaction cost, and simpler downstream purification, indicating the potential utility of LkADH-D18 in future industrial applications.
Deep Eutectic Solvents as Media in Alcohol Dehydrogenase-Catalyzed Reductions of Halogenated Ketones
Ibn Majdoub Hassani, Fatima Zohra,Amzazi, Saaid,Kreit, Joseph,Lavandera, Iván
, p. 832 - 836 (2019/12/24)
The application of deep eutectic solvents (DESs) in biotechnological processes has gained an outstanding relevance, as they can be used as greener media to obtain higher productivities and selectivities. In the present contribution, an eutectic mixture composed of choline chloride (ChCl): glycerol (1 : 2 mol/mol) has been used as a reaction medium in combination with Tris?SO4 50 mM buffer pH 7.5, applied to the alcohol dehydrogenase (ADH)-catalyzed reduction of various carbonyl precursors of chiral halohydrins. These alcohols are key intermediates of biologically active compounds, and hence they are of industrial interest. In the presence of up to 50 % v/v of DES, these biotransformations were achieved up to 300–400 mM of the α-halogenated ketone substrate, getting access to the final compounds with excellent conversions (usually >90 %) and enantiomeric excess (ee >99 %). Among the different ADHs tested, two stereocomplementary enzymes (Lactobacillus brevis ADH and Rhodococcus ruber ADH) afforded the best results, so both alcohol enantiomers could be obtained in all the studied examples. Selected bioreductions were scaled up to 250 mg and 1 g, demonstrating the potential that DESs can offer as media in redox processes for substrates with low solubility in water.
