Enzymatic Late-Stage Modifications: Better Late Than Never

Area of Science:

• Synthetic Chemistry
• Biocatalysis
• Drug Development

Background:

• Enzyme catalysis is increasingly vital in synthetic chemistry.
• Bioinformatics and enzyme engineering provide diverse biocatalysts for selective reactions.
• Biocatalysis excels in late-stage modifications, often outperforming de novo synthesis.

Purpose of the Study:

• To review the strengths and limitations of enzymatic late-stage modifications.
• To highlight the application of native and engineered enzymes in synthesis.
• To focus on key examples in drug development.

Main Methods:

• Utilizing bioinformatics and enzyme engineering to develop biocatalysts.
• Applying enzymes for direct functionalization of complex scaffolds.
• Employing enzymes for rapid diversification of compound libraries.

Main Results:

• Enzymatic oxyfunctionalizations, halogenations, methylations, reductions, and amide bond formations are crucial.
• These enzymatic reactions are highly prevalent in pharmaceutical compounds.
• Enzymes enable efficient introduction of functional groups and library diversification.

Conclusions:

• Enzymatic late-stage modification is a powerful strategy in modern synthesis.
• Engineered enzymes offer expanded capabilities for complex chemical transformations.
• Biocatalysis plays a significant role in accelerating drug discovery and development.