Green and Enantioselective Synthesis via Cascade Biotransformations: From Simple Racemic Substrates to High-Value Chiral Chemicals.

Autor: Yi J; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore., Goh NJJ; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore., Li Z; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.
Jazyk: angličtina
Zdroj: Chemistry, an Asian journal [Chem Asian J] 2024 Oct 01; Vol. 19 (19), pp. e202400565. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1002/asia.202400565
Abstrakt: Asymmetric synthesis of chiral chemicals in high enantiomeric excess (ee) is pivotal to the pharmaceutical industry, but classic chemistry usually requires multi-step reactions, harsh conditions, and expensive chiral ligands, and sometimes suffers from unsatisfactory enantioselectivity. Enzymatic catalysis is a much greener and more enantioselective alternative, and cascade biotransformations with multi-step reactions can be performed in one pot to avoid costly intermediate isolation and minimise waste generation. One of the most attractive applications of enzymatic cascade transformations is to convert easily available simple racemic substrates into valuable functionalised chiral chemicals in high yields and ee. Here, we review the three general strategies to build up such cascade biotransformations, including enantioconvergent reaction, dynamic kinetic resolution, and destruction-and-reinstallation of chirality. Examples of cascade transformations using racemic substrates such as racemic epoxides, alcohols, hydroxy acids, etc. to produce the chiral amino alcohols, hydroxy acids, amines, and amino acids are given. The product concentration, ee, and yield, scalability, and substrate scope of these enzymatic cascades are critically reviewed. To further improve the efficiency and practical applicability of the cascades, enzyme engineering to enhance catalytic activities of the key enzymes using the latest microfluidics-based ultrahigh-throughput screening and artificial intelligence-guided directed evolution could be a useful approach.
(© 2024 The Authors. Chemistry - An Asian Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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