(S)-2-Chloro-1-(3,4-difluorophenyl)ethanol
(1) is a vital chiral intermediate for the synthesis
of Ticagreloran effective treatment for acute coronary syndromes.
A ketoreductase (KRED) KR-01 in our KRED library was screened to transform
2-chloro-1-(3,4-difluorophenyl)ethanone (2) into the
chiral alcohol 1. During process optimization, the bioreduction
procedure was performed at a substrate concentration of 500 g/L, giving
a near 100% conversion with >99.9% ee. The product 1 was
directly obtained by extraction and can be used for the synthesis
of (1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylic
acid ethyl ester (3) with a yield of 98% and >99.9%
de,
greatly simplifying the original process operation and reducing the
safety risk. This process is green and environmentally sound with
high productivity of biocatalysis and a space–time yield of
145.8 mmol/L/h. It has an opportunity to be very useful in industrial
applications. Additional studies have indicated that KR-01 can also
be used to prepare (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol
(4) with a substrate concentration of 500g/L.
A chemoenzymatic synthesis of the veterinary antibiotic florfenicol is described. The key step involves the dynamic reductive kinetic resolution (DYRKR) of a keto ester by using a ketoreductase‐02 (KRED‐02) to afford the two contiguous stereocenters of the (2S,3R)‐cis‐1,2‐amino alcohol intermediate in >99 % ee and a diastereomeric ratio (dr) of 99 %. This green biocatalysis is environmental friendly with high enantioselectivity and product yields. Two methods for the nucleophilic fluorination step involved the use of aziridines and cyclic sulfates to safely prepare fluoroamines with high regioselectivity. Additional studies have indicated that KRED‐02 can also be used to afford chiral alcohol (S)‐21 in good yields with high enantioselectivity. This study shows that the integration of biocatalysis into organic synthesis can be useful and provide industrial opportunities for applications of florfenicol.
Third-row transition-metal complexes remained as a key component in preparation of light emitting layer for future OLED technology. Hence, it is utmost important to expand their emission peak wavelengths into...
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 coli expressing LK08, a ketoreductase mutant from Lactobacillus kefiri, as a biocatalyst. The reaction conditions for the biotransformation including pH, temperature, and concentration of isopropanol and NADP + , as well as the amount of recombinant E. coli cells, were optimized to improve the process productivity. When the enzymatic process was carried out on a 300 g scale under the optimized conditions, the ketone 2 was fully converted to chiral alcohol 3 with a product ee value of >99%. Furthermore, 3 was isolated and used to chemically synthesize luliconazole with 38% yield and 99% ee. This study presents an efficient and cost-effective chemoenzymatic process for the production of (R)-E-1.
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