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Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases
Author(s) -
Zou Jie,
Ni Guowei,
Tang Jiawei,
Yu Jun,
Jiang Luobin,
Ju Dianwen,
Zhang Fuli,
Chen Shaoxin
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800658
Subject(s) - florfenicol , chemistry , biocatalysis , kinetic resolution , stereocenter , diastereomer , regioselectivity , nucleophile , enantioselective synthesis , alcohol , green chemistry , combinatorial chemistry , stereochemistry , organic chemistry , ionic liquid , catalysis , antibiotics , biochemistry
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 (2 S ,3 R )‐ 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.