Evolving New Chemistry: Biocatalysis for the Synthesis of Amine-Containing Pharmaceuticals.

Zawodny, Wojciech; Montgomery, Sarah Louise

Biocatalysis has become an attractive tool in modern synthetic chemistry both in academic and industrial settings, offering access to enantiopure molecules. In industry, biocatalysis found use in small molecule pharmaceutical development. For several amine-containing drugs, biotransformations were applied in the process routes, improving the original syntheses employing classical chemical methods. This review illustrates how and why biocatalysis has been applied to create safer, more efficient and less costly processes for the manufacture of chiral amine-containing pharmaceuticals and alkaloids. Several enzyme classes have been applied to syntheses of natural products, pharmaceutical products and their intermediates, including transaminases, imine reductases, monoamine oxidases and Pictet-Spenglerases. The routes with and without application of biocatalysis are compared, and the potential of these enzyme classes in redesigned synthetic routes to natural products, alkaloids and high-value chemicals is evaluated, using syntheses of sitagliptin, suvorexant, PF-04449913, MK-7246, vernakalant, GSK-2879552, boceprevir and (−)-strictosidine as examples. Application of biocatalysis in the synthesis of amine-containing pharmaceuticals constitutes a greener alternative to transition metal-catalysed routes, facilitates installation of chiral amine functionalities at a late stage of the synthesis and provides exquisite stereocontrol. Opportunities and challenges of biocatalysis for the synthesis of chiral amines are reviewed with respect to use in drug discovery and development.

SMALL molecules; BIOCATALYSIS; MANUFACTURING processes; REDUCTASES; NATURAL products; DRUG discovery; FORMYLATION; RIBONUCLEOSIDE diphosphate reductase

Catalysts (2073-4344), 2022, Vol 12, Issue 6, pN.PAG

2073-4344

Academic Journal

10.3390/catal12060595