Chemoenzymatic Synthesis of Fluorinated L-α-Amino Acids
化学
氨基酸
立体化学
有机化学
生物化学
作者
Xuerui Jin,Chaoqun Huang,Can Cui,Huayi Liu,Haibo Liu,Dawen Niu,Yunzi Luo
出处
期刊:ACS Sustainable Chemistry & Engineering [American Chemical Society] 日期:2024-08-27
标识
DOI:10.1021/acssuschemeng.4c05318
摘要
Fluorinated amino acids play a crucial role as fundamental components in drug synthesis owing to their favorable attributes that enhance the pharmacokinetic properties of drugs. Nevertheless, the conventional chemical synthesis of fluorinated amino acids faces challenges in achieving stereoselectivity control. Additionally, the high cost of substrates and the intricate cofactor recycling process in enzymatic synthesis have limited their industrial production and applications. In this study, we developed a three-step chemoenzymatic cascade for the asymmetric synthesis of chiral fluorinated amino acids. The methodology involves the utilization of a variety of cost-effective aldehydes as starting materials, enabling economical aldol reactions catalyzed by aldolase. Subsequent chemical decarboxylation produces substrates for reductive amination through phenylalanine ammonia lyase, resulting in a diverse library of fluorinated aromatic l-α-amino acid products with a relative high yield and high enantiomeric purity (up to 99%). Furthermore, we synthesized three pharmaceutically relevant fluorinated l-α-amino acids on a preparative scale using whole-cell biocatalysts, demonstrating the versatility of the approach. This study has introduced a simplified, efficient, and cost-effective route for synthesizing fluorinated l-α-amino acids under mild conditions, offering insights into the production of valuable fluorine-containing pharmaceuticals and other biologically active compounds.