Asymmetric Synthesis of Florfenicol by Dynamic Reductive Kinetic Resolution with Ketoreductases. Issue 36 (30th July 2018)

• Record Type: Journal Article
• Authors: Zou, Jie; Ni, Guowei; Tang, Jiawei; Yu, Jun; Jiang, Luobin; Ju, Dianwen; Zhang, Fuli; Chen, Shaoxin
• Is Part Of: European journal of organic chemistry. Issue 36(2018)
• Page Start: 5044
• Page End: 5053
• Publication Date: 2018-07-30
• Subjects: Asymmetric synthesis -- Kinetic resolution -- Enzymes -- Fluorine -- Regioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201800658
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : Chemoenzymatic synthesis: The preparation of florfenicol features the use of enzymatic dynamic reductive kinetic resolution (DYRKR) to establish the two stereocenters of the cis ‐1, 2‐amino alcohol intermediate with >99 % ee and a diastereomeric ratio ( dr ) of 99 %. The treatment of aziridines and cyclic sulfates with Et3 N‐3HF was used to introduce the fluorine atom with high regioselectivity.