Dehydroamino acids: chemical multi-tools for late-stage diversification

Area of Science:

• Organic Chemistry
• Biochemistry
• Chemical Biology

Background:

• α,β-Dehydroamino acids (dhAAs) are noncanonical amino acids found in natural products.
• dhAAs possess significant synthetic flexibility, enabling various chemical transformations.
• They serve as orthogonal chemical handles for late-stage biomolecule modification under mild conditions.

Purpose of the Study:

• To provide a comprehensive overview of the chemical reactivity of dhAAs.
• To highlight recent advancements in adapting dhAA transformations for biomolecules.
• To discuss biocatalytic alternatives for dhAA modification.

Main Methods:

• Review of existing literature on dhAA reactivity.
• Emphasis on recent studies adapting dhAA chemistry for peptides and proteins.
• Exploration of enzymes involved in natural product biosynthesis catalyzing similar reactions.

Main Results:

• dhAAs undergo diverse reactions including additions, cross-couplings, and cycloadditions.
• Recent efforts have focused on applying dhAA chemistry to natural products, peptides, and proteins.
• Enzymes offer biocatalytic routes for regio- and stereoselective dhAA modifications.

Conclusions:

• The inherent reactivity of dhAAs offers a broad scope for chemical biology applications.
• Further research into dhAA chemistry will yield novel tools for drug discovery.
• Biocatalytic approaches using enzymes present promising alternatives for dhAA functionalization.