Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs

Process implementation aspects for biocatalytic hydrocarbon oxyfunctionalization.

The chiral feature is a critical factor for the efficacy and safety of many therapeutic agents. At present, about 57% of marketed drugs are chiral drugs and about 99% of purified natural products are chiral compounds. There has been a tremendous potential of functional microorganisms and biocatalysts derived from them for the bioconversion of synthetic chemicals into drugs with high enantio-, chemo-, and regio-selectivities. Biocatalysis is becoming a key subassembly in the medicinal chemist’s toolbox. In fact, the intermediates of many important therapeutic agents such as sitagliptin, pregabalin, ragaglitazar, paclitaxel, epothilone, abacavir, atorvastatin, rosuvastatin, and omapatrilat have been successfully synthesized via biocatalysis. In this review, various biocatalytic systems that enable to synthesize these chiral drug intermediates are updated and discussed regarding their potential application in the pharmaceutical industry. Further development and increased utilization of biocatalysis for production of drugs with emphasis on green chemistry can be expected.

Synthesizing Chiral Drug Intermediates by Biocatalysis

Fine chemicals are pure molecules useful as synthesis intermediates or as final products. REACH normative and the new environmental protection laws in the United States, Japan, and European Union support the change of conventional synthesis procedures into some other more innovative, more environmentally safe, and nontoxic for human health procedures, by using green solvents, raw materials from renewable sources, etc. In addition, the application of more and more efficient catalysts is one of the main challenges in the industry. Biocatalysts are the most efficient catalysts and so, biocatalyzed synthesis of fine chemicals is opening a new innovative future for the chemical–biological industries. As a consequence, the chemical market is one of the most interesting fields in the future for biocatalysis and white biotechnology. In this article, we describe the fundaments of the biocatalyzed reactions and the types of enzymes used, and discuss the application of genetically modified microorganisms, wild-type whole cells, or isolated enzymes (native or immobilized). We show different examples of the preparation of fine chemicals using biocatalysts and the importance of these processes in the food, feed, and pharmaceutical industries.

Biocatalyzed Production of Fine Chemicals

An Efficient Synthesis of 2-Quinoxalinecarboxylic Acid

Biocatalytic Oxidation of 2-Methylquinoxaline to 2-Quinoxalinecarboxylic Acid

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Biocatalytic Oxidation of 2-Methylquinoxaline to 2-Quinoxalinecarboxylic Acid