BioChem - DOS

Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases

European journal of organic chemistry

Zou, Jie; Ni, Guowei; Tang, Jiawei; Yu, Jun; Jiang, Luobin; Ju, Dianwen; Zhang, Fuli; Chen, Shaoxin

<P>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&#8208;02 (KRED&#8208;02) to afford the two contiguous stereocenters of the (2<I>S</I>,3<I>R</I>)&#8208;<I>cis</I>&#8208;1,2&#8208;amino alcohol intermediate in >99 % <I>ee</I> and a diastereomeric ratio (<I>dr</I>) 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&#8208;02 can also be used to afford chiral alcohol (<I>S</I>)<B>&#8208;21</B> 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.</P>

2018

1434-193x

1099-0690

2018

36

pp.5044-5053

10.1002/ejoc.201800658

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART89632943

Asymmetric synthesis; Kinetic resolution; Enzymes; Fluorine; Regioselectivity