[Development of Selective Reactions in the Synthesis of Medicines].

Abstract

This review summarizes the contributions to the discovery, evaluation, and functional development of microbial and enzyme catalysts, as well as the rational design of pathways that synergistically integrate chemical and biochemical reactions. In the introduction, the author outlines his strategies and principles: 1) He avoided biosynthetic enzymes and pathways, opting instead for degradative enzymes that offer broader substrate flexibility and a wider range of applications. 2) He focused on commercially available enzymes, prioritizing their reproducibility and accessibility for widespread use. All the microorganisms he identified have been deposited in public institutions, making them available to researchers in both academic and corporate settings. 3) He developed methods to enhance reactivity and selectivity by optimizing reaction conditions and substrate structures, without altering the enzymes themselves. The main body of the review is divided into two parts. Part 1, titled "Chemo-enzymatic Synergistic Synthesis of Medicines," covers the following topics: 1) the synthesis of dihydroxymethylepoxyquinomicin (DHMEQ); 2) the synthesis of sialic acids; 3) the utilization of epoxide hydrolase; and 4) the synthesis of (S)-azetidine-2-carboxylic acid. Part 2, titled "New Selective Reactions for Synthesis of Medicines," includes: 1) the optimization of reaction conditions in lipase-catalyzed transesterification and aminolysis; 2) the conversion of racemates into single enantiomers using hydrolytic enzymes through novel pathways; 3) the use of carbonyl reductases in conjunction with substrate design; 4) nitrile hydratase and amidase in Rhodococcus species; 5) selective acylation and deacylation of alcohols and phenols; and 6) the use of oligosaccharides as protective groups in the synthesis of polyphenol glycosides.