Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods.

Area of Science:

• Biocatalysis and Organic Synthesis
• Pharmaceutical Chemistry
• Green Chemistry

Background:

• Biocatalysis leverages enzymes for organic synthesis, evolving from early whole-cell methods to highly engineered enzymes via molecular biology.
• Advances in gene sequencing and directed evolution have enabled the development of robust enzymes with tailored specificities for API synthesis.
• Enzymes are increasingly used to create shorter, more efficient, and sustainable synthetic routes for active pharmaceutical ingredients (APIs).

Purpose of the Study:

• To compare large-scale biocatalytic synthetic routes with traditional chemical protocols for over 130 APIs.
• To analyze differences in steps, reaction conditions, and scale between biocatalytic and chemical synthesis.
• To highlight the advantages of biocatalysis in API manufacturing.

Main Methods:

• Review of large-scale synthetic routes for >130 APIs and drug candidates.
• Comparison of biocatalytic key steps with corresponding chemical protocols.
• Analysis structured by the functional group formed in the reaction.

Main Results:

• Biocatalytic routes offer shorter, more efficient, and sustainable alternatives to chemical synthesis for numerous APIs.
• Enzymes enable tailored selectivities and broad substrate scopes, improving API production.
• Comparison reveals significant advantages in reaction conditions and scale for biocatalytic processes.

Conclusions:

• Biocatalysis is a key enabling technology for modern, sustainable API synthesis.
• Enzymatic methods provide efficient and selective routes for established and novel APIs.
• The review provides a comprehensive resource for comparing biocatalytic and chemical synthetic strategies in pharmaceutical manufacturing.