7.19 C–X Bond Formation: Enzymatic Enantioselective Decarboxylative Protonation and C–C Bond Formation

Abstract

The implementation of biocatalysts in environmentally sustainable industrial biotechnology-based processes has become increasingly important in the production of biofuels, bulk chemicals, fine chemicals, and other products. Notably, enzymes have been developed to produce enantiomerically pure compounds required for the manufacture of pharmaceuticals. Such processes have potential advantages over other nonenzymatic asymmetric synthesis, including higher chemo-, regio-, and enantioselectivities. In addition, the application of purified enzymes, immobilized enzymes, and whole-cell biocatalysts can alleviate the need for organic solvents and other toxic and undesirable reagents and catalysts. Here, the focus is on the decarboxylase enzymes and their value in the preparation of homochiral compounds. Firstly, the decarboxylases that catalyze reactions leading to asymmetric CH bonds formation will be discussed. These decarboxylases, which catalyze enantioselective decarboxylative protonation reactions, include l-aspartate-β-decarboxylase, which produces enantiopure amino acids; α-acetolactate decarboxylases for chiral ketol formation; and malonic semialdehyde decarboxylase and the arylmalonate decarboxylases for chiral carboxylic acids from β-hydroxy carboxylates and prochiral malonates, respectively. In addition, decarboxylases that catalyze enantioselective decarboxylative asymmetric CC bond formation will also be highlighted. Such enzymes include serine hydroxymethyltransferases that facilitate β-hydroxy-l-α-amino acid formation from glycine, and the pyruvate, phenylpyruvate, and benzoylformate decarboxylases, capable of synthesizing chiral benzoins.