256474-24-5

Usage

Uses

Used in Pharmaceutical and Agrochemical Industries:
(S)-2-CHLORO-1-(3,4-DICHLOROPHENYL)ETHANOL is used as an intermediate in the synthesis of various pharmaceuticals and agrochemicals, contributing to the development of new drugs and pesticides. Its chiral nature is particularly important in these applications, as the stereochemistry of a compound can significantly affect its biological activity and efficacy.
Used in Research and Development:
(S)-2-CHLORO-1-(3,4-DICHLOROPHENYL)ETHANOL is also used in research and development settings, where it is studied for its potential antibacterial and antifungal properties. The exploration of these properties could lead to the discovery of new treatments for bacterial and fungal infections.
Used in Organic Synthesis:
(S)-2-CHLORO-1-(3,4-DICHLOROPHENYL)ETHANOL serves as a building block in organic synthesis, enabling the creation of new compounds with diverse applications. Its unique structure and reactivity make it a valuable component in the development of novel chemical entities for various industries.

Upstream product

• 4128-31-8 rac-octan-2-ol 
• 42981-08-8 2,3',4'-trichloroacetophenone 

Downstream Products

• 256474-26-7 (S)-(+)-(3,4-Dichlorophenyl)oxirane 

Relevant academic research and scientific papers

Unmasking the Hidden Carbonyl Group Using Gold(I) Catalysts and Alcohol Dehydrogenases: Design of a Thermodynamically-Driven Cascade toward Optically Active Halohydrins

A concurrent cascade combining the use of a gold(I) N-heterocyclic carbene (NHC) and an alcohol dehydrogenase (ADH) is disclosed for the synthesis of highly valuable enantiopure halohydrins in an aqueous medium and under mild reaction conditions. The meth

Deep Eutectic Solvents as Media in Alcohol Dehydrogenase-Catalyzed Reductions of Halogenated Ketones

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.

Efficient Synthesis of (R)-2-Chloro-1-(2,4-dichlorophenyl)ethanol with a Ketoreductase from Scheffersomyces stipitis CBS 6045

By enzyme screening, a ketoreductase cloned from Scheffersomyces stipitis CBS 6045 and named SsCR was identified that could catalyze the asymmetric hydrogenation of a variety of aromatic ketones. SsCR exhibited a specific activity of 65 U mg?1p

Reconstruction of the Catalytic Pocket and Enzyme–Substrate Interactions To Enhance the Catalytic Efficiency of a Short-Chain Dehydrogenase/Reductase

To upgrade the short-chain dehydrogenase/reductase EbSDR8 to a powerful tool for the synthesis of antiPrelog chiral alcohols, rational design was performed by reconstructing the catalytic pocket and enzyme–substrate interactions. The resulting variants showed significantly improved catalytic efficiency (kcat/KM; kcat=turnover rate, KM=Michaelis constant) towards a series of prochiral ketones, with kcat/KM values more than 15-fold greater than that of wildtype EbSDR8 in some cases. More importantly, none of the mutations caused an adverse effect on the stereoselectivity. The increased steric repulsion and the C?H???π interaction involving the alkyl side chain of L153 and the phenyl ring of the substrate turned out to be crucial factors connected to the enhanced enzymatic activity. This provided new insight into the role of steric hindrance and non canonical interactions in protein engineering. Furthermore, the recombinant E. coli whole cells expressing the EbSDR8 variant G94A/S153L successfully catalyzed the reduction of a high-concentration 2,2,2-trifluoroacetophenone. The results demonstrated the effectiveness of rational design and the applicability of the designed variants in the efficient reduction of prochiral ketones.

Enantioselective bioreductive preparation of chiral halohydrins employing two newly identified stereocomplementary reductases

Two robust stereocomplementary carbonyl reductases (DhCR and CgCR) were identified through rescreening the carbonyl reductase toolbox. Five reductases were returned through the activity and enantioselectivity assay for α-chloro-1-acetophenone and ethyl 4-chloro-3-oxo-butanate (COBE). Three reductases were stable at elevated substrate loading. Enzymatic characterization revealed that DhCR and CgCR were more thermostable. As much as 330 g COBE in 1 L biphasic reaction mixture was reduced to (S)- and (R)-3-hydroxy-4-chlorobutyrate by DhCR and CgCR (coexpressed with glucose dehydrogenase), with 92.5% and 93.0% yields, >99% ee, and total turnover numbers of 53800 and 108000, respectively. Six other α-halohydrins were asymmetrically reduced to optically pure forms at a substrate loading of 100 g L-1. Our results indicate the potential of these two stereocomplementary reductases in the synthesis of valuable α-halohydrins for pharmaceuticals. This journal is

Characterization of an excellent anti-Prelog short-chain dehydrogenase/reductase EbSDR8 from Empedobacter brevis ZJUY-1401

Empedobacter brevis ZJUY-1401 is capable of producing anti-Prelog alcohols with excellent stereoselectivity. The gene encoding a short-chain dehydrogenase/reductase from E. brevis ZJUY-1401 (EbSDR8) was cloned and heterologously expressed in Escherichia coli, and the purified recombinant protein was characterized. The subunit of EbSDR8 is composed of 250 amino acids with a calculated molecular mass of 26.4 kDa. Important properties regarding the application of EbSDR8 include utilization of cheaper coenzyme, the excellent catalytic performance over a broad pH range from 7.0 to 10.5, and temperature optimum of 35 °C. The enzyme showed moderate thermostability, with half-lives of 4.4 h at 35 °C and 3.1 h at 45 °C, respectively. In the presence of isopropanol as a cosubstrate, the whole-cell of recombinant E. coli expressing EbSDR8 could efficiently catalyze the asymmetric reduction without addition of any NADH into the reaction system. EbSDR8 displayed good activity and excellent stereoselectivity toward a spectrum of acetophenone derivatives, providing anti-Prelog alcohols with >99% ee for the majority of the substrates. These results suggest that EbSDR8 is a powerful chiral tool for the production of anti-Prelog alcohols.

Biocatalytic anti-Prelog reduction of prochiral ketones with whole cells of a newly isolated strain Empedobacter brevis ZJUY-1401

Robust biocatalysts are in high demand for the reduction of prochiral ketones to anti-Prelog chiral alcohols. A recently isolated bacterial strain ZJUY-1401 exhibited high reduction activity and excellent anti-Prelog stereospecificity toward prochiral ketones. Based on the colony and microscopic morphology, physiological tests, and 16S rDNA sequence, the isolate was identified as Empedobacter brevis. Upon addition of either NADH or NADPH, the whole cells of E. brevis ZJUY-1401 showed enhanced catalytic activity. The activity and stereoselectivity of the biocatalyst toward acetophenone were significantly increased in the presence of 10% (v/v) ethanol as cosubstrate. Important properties concerning the application of E. brevis ZJUY-1401 include the excellent catalytic performance over a broad pH range from 6.0 to 9.5, temperature optimum of 35 °C, and noticeable tolerance against ethanol. Under the optimal conditions, E. brevis ZJUY-1401 was highly active for the reduction of acetophenone derivatives, giving corresponding alcohols in excellent enantiomeric purity (>99% ee). These results imply that E. brevis ZJUY-1401 is a promising biocatalyst for the preparation of anti-Prelog chiral alcohols.

Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii

Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers. Copyright

Enzymatic ketone reduction: mapping the substrate profile of a short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae

A short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae was cloned and expressed in Escherichia coli, and the encoded protein was purified. The activity and enantioselectivity of this recombinant enzyme were evaluated with a series of ketones. The alcohol dehydrogenase (YMR226c) was found to effectively catalyze the enantioselective reductions of aryl-substituted acetophenones, α-chloroacetophenones, aliphatic ketones, and α- and β-ketoesters. While the enantioselectivity for the reduction of β-ketoesters was moderate, the acetophenone derivatives, aromatic α-ketoesters, some substituted α-chloroacetophenones, and aliphatic ketones were reduced to the corresponding chiral alcohols with excellent enantioselectivity. The enantiopreference of this enzyme generally followed Prelog's rule for the simple ketones. The ester functionality played some role in determining the enzyme's enantiopreference for the reduction of α- and β-ketoesters. The present study serves as a valuable guidance for the future applications of this versatile biocatalyst.