Biocatalysis: An Industrial Perspective
CHAPTER 5: Bristol-Myers Squibb: Preparation of Chiral Intermediates for the Development of Drugs and APIs
Published:02 Nov 2017
Special Collection: 2017 ebook collectionSeries: Catalysis Series
R. N. Patel, in Biocatalysis: An Industrial Perspective, ed. G. de Gonzalo and P. Domínguez de María, The Royal Society of Chemistry, 2017, pp. 125-167.
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The production of single enantiomers of key chiral intermediates has become increasingly important for the development of drugs. Demand for chiral compounds continues to rise in the pharmaceutical industry due to federal regulations covering active pharmaceutical ingredients (APIs), and the recognition that enantiomers of a chiral compound could have dramatically different biological activities and toxicity. In this area, there are a number of advantages in using biocatalysis over chemical synthesis. Typically, enzyme-catalyzed reactions are highly enantioselective, regioselective and do not require protection and deprotection steps during synthesis. They can be carried out at ambient temperature, atmospheric pressure in aqueous systems, and are often regarded as green processes that avoid the use of more extreme conditions used in chemical reactions which could cause undesirable side reactions. Microbial cells and enzymes (biocatalysts) can be immobilized and reused for many cycles, and enzymes are generally over-expressed in suitable hosts such as Escherichia coli to make enzymatic processes economically efficient, safer and cheaper. The preparation of thermostable, pH stable, organic solvent tolerant and highly active biocatalysts towards substrates by random and site-directed mutagenesis by directed evolution has led to the production of novel biocatalysts to be used under desired process conditions. This chapter describes the synthesis of key intermediates for the synthesis of APIS by biocatalysis at Bristol-Myers Squibb to provide sustainable, energy efficient and economical processes.