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.
Lipase mediated enzymatic kinetic resolution of phenylethyl halohydrins acetates: A case of study and rationalization
Fonseca, Thiago de Sousa,Vega, Kimberly Benedetti,da Silva, Marcos Reinaldo,de Oliveira, Maria da Concei??o Ferreira,de Lemos, Telma Leda Gomes,Contente, Martina Letizia,Molinari, Francesco,Cespugli, Marco,Fortuna, Sara,Gardossi, Lucia,de Mattos, Marcos Carlos
, (2020/02/18)
Racemic phenylethyl halohydrins acetates containing several groups attached to the aromatic ring were resolved via hydrolysis reaction in the presence of lipase B from Candida antarctica (Novozym 435). In all cases, the kinetic resolution was highly selective (E > 200) leading to the corresponding (S)-β-halohydrin with ee > 99 %. However, the time required for an ideal 50 % conversion ranged from 15 min for 2,4-dichlorophenyl chlorohydrin acetate to 216 h for 2-chlorophenyl bromohydrin acetate. Six chlorohydrins and five bromohydrins were evaluated, the latter being less reactive. For the β-brominated substrates, steric hindrance on the aromatic ring played a crucial role, which was not observed for the β-chlorinated derivatives. To shed light on the different reaction rates, docking studies were carried out with all the substrates using MD simulations. The computational data obtained for the β-brominated substrates, based on the parameters analysed such as NAC (near attack conformation), distance between Ser-O and carbonyl-C and oxyanion site stabilization were in agreement with the experimental results. On the other hand, the data obtained for β-chlorinated substrates suggested that physical aspects such as high hydrophobicity or induced change in the conformation of the enzymatic active site are more relevant aspects when compared to steric hindrance effects.
