Biocatalysis: Synthesis of Key Intermediates for Development of Pharmaceuticals

Abstract

Chirality is a key factor for the safety and efficacy of many drug products. The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. There has been an enormous potential of microorganisms and enzymes derived from there for the transformation of synthetic chemicals with high chemo-, regio-, and enatioselectivities. Recent development in the area of directed evolution has led screen mutants under process conditions to increase activity and selectivity of biocatalysts, thus making the enzymatic process highly efficient and economically feasible. In this review, chemoenzymatic processes are described for the synthesis of chiral intermediates for the development of pharmaceuticals.

Flavoprotein oxidases: classification and applications

“…For examples of this elegant approach for deracemisation of amines, the reader is referred to a recent review of Turner (2011). Amine-oxidising oxidases have also been combined with other enzymes for the preparation of enantiopure amines (Patel 2011). For example, in 2011, enantiopure (S)-amino-3-[3-{6-(2methylphenyl)}pyridyl]-propionic acid was synthesised in 72% yield from the racemic amino acid by combining the (R)-amino acid oxidase from Trigonopsis variabilis with (S)-aminotransferase from Sporosarcina urea (Patel et al 2007).…”

Immobilization of lipases on glyoxyl–octyl supports: Improved stability and reactivation strategies

“…Enzymes are very interesting [1][2][3][4][5][6][7] but they also have some limitations as industrial biocatalysts [8]. This occurs for example with the moderate stability of enzymes under conditions sometimes required by industry [9,10].…”

Changes on enantioselectivity of a genetically modified thermophilic lipase by site-directed oriented immobilization

“…Improvement of enzyme selectivity is a crucial issue for a green synthesis of natural products and pharmaceuticals [1][2][3][4].…”