Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases

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

来源：European Journal of Organic Chemistry, 2018, 2018(36): 5044-5053.

DOI：10.1002/ejoc.201800658

• Asymmetric synthesis
• Kinetic resolution
• Enzymes
• Fluorine
• Regioselectivity

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.

• 出版日期2018-9-30
• 单位复旦大学; 上海医药工业研究院