Efficient enzymatic synthesis of (S)-1-(3′-bromo-2′-methoxyphenyl)ethanol, the key building block of lusutrombopag

Autor: Yunfeng Cui, Yangyang Ji, Xi Chen, Jianjiong Li, Jinhui Feng, Qing Zhao, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Green Synthesis and Catalysis, Vol 4, Iss 3, Pp 268-271 (2023)
Druh dokumentu: article
ISSN: 2666-5549
DOI: 10.1016/j.gresc.2022.06.010
Popis: (S)-1-(3′-Bromo-2′-methoxyphenyl)ethanol ((S)-1b) is the key precursor for the synthesis of Lusutrombopag. The bioreduction of 1-(3′-bromo-2′-methoxyphenyl)ethanone (1a) offers an attractive method to access this important compound. Through screening the available carbonyl reductases, we obtained a carbonyl reductase from Novosphingobium aromaticivorans (CBR), which could completely convert 100 ​g/L of 1a to (S)-1b. Furthermore, a carbonyl reductase from Novosphingobium sp. Leaf2 (NoCR) was identified to completely convert 200 ​g/L of 1a to (S)-1b with excellent enantioselectivity (>99% ee) and 77% isolated yield using FDH/formate system for NADH regeneration. The Km and kcat of recombinant NoCR towards 1a were 0.66 ​mmol/L and 7.5 s-1, and the catalytic efficiency kcat/Km was 11.3 ​mmol/s.L. Meanwhile, NoCR showed high catalytic activity and stereoselectivity towards acetophenone derivatives with halogen or methoxy substitution on the benzene ring, indicating that NoCR is a valuable biocatalyst with potential practical applications.
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