ENZYMES AT WORK: Rapid screening and optimization of enzymatic activity, along with available, easy-to-use enzymes, are making biocatalysis a handy tool for chiral synthesis

Abstract

CHEMISTS HAVE BEEN PRACTICING ORGANIC CHEMISTRY for hundreds of years; microbes have been at it even longer. Microbial and other enzymes are superbly enantio-, chemo-, and regioselective across a diverse range of reactions under mild conditions of pH, temperature, and pressure. Why, then, has it taken chemists so long to put aside a dislike of "bugs" and use their enzyme catalysts? The question is especially pertinent when it comes to making pharmaceuticals. When scientists at GlaxoSmithKline, AstraZeneca, and Pfizer examined 128 syntheses from their own companies, they found that as many as half of the drug compounds made by their process R&D groups are not only chiral but also contain an average of two chiral centers each ( Org. Biomol Chem. 2006,4,2337). And to meet regulatory requirements, enantiomeric purities of 99.5% were found to be necessary. "When it comes to wanting selectivities of 98% or higher, you are probably bound to a bioprocess, because getting beyond ...