Journal
CHEMICAL REVIEWS
Volume 122, Issue 1, Pages 1052-1126Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.1c00574
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Funding
- European Union [862081, 764920]
- BMK
- BMDW
- SFG
- Standortagentur Tirol
- Government of Lower Austria
- Vienna Business Agency
- University of Graz
- Field of Excellence BioHealth
- Marie Curie Actions (MSCA) [764920] Funding Source: Marie Curie Actions (MSCA)
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Biocatalysis, using enzymes for organic synthesis, is a powerful tool for the synthesis of active pharmaceutical ingredients (APIs). Developments in molecular biology methods have led to the rapid development of process-stable enzymes through directed evolution. Enzymes are widely employed in the synthesis of small molecule APIs, enabling more efficient and sustainable routes.
Biocatalysis, using enzymes for organic synthesis, has emerged as powerful tool for the synthesis of active pharmaceutical ingredients (APIs). The first industrial biocatalytic processes launched in the first half of the last century exploited whole-cell microorganisms where the specific enzyme at work was not known. In the meantime, novel molecular biology methods, such as efficient gene sequencing and synthesis, triggered breakthroughs in directed evolution for the rapid development of process-stable enzymes with broad substrate scope and good selectivities tailored for specific substrates. To date, enzymes are employed to enable shorter, more efficient, and more sustainable alternative routes toward (established) small molecule APIs, and are additionally used to perform standard reactions in API synthesis more efficiently. Herein, large-scale synthetic routes containing biocatalytic key steps toward >130 APIs of approved drugs and drug candidates are compared with the corresponding chemical protocols (if available) regarding the steps, reaction conditions, and scale. The review is structured according to the functional group formed in the reaction.
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