Inverse Peptide Synthesis Using Transient Protected Amino Acids.

Area of Science:

• Organic Chemistry
• Green Chemistry
• Biochemistry

Background:

• Traditional peptide synthesis requires protecting and deprotecting the α-amino group, hindering sustainable development.
• Using unprotected amino acids is a desirable green strategy but has been unsuccessful due to severe epimerization during N→C elongation.

Purpose of the Study:

• To overcome the challenge of epimerization in peptide synthesis using unprotected amino acids.
• To develop a practical and sustainable protocol for green peptide synthesis.

Main Methods:

• A novel ynamide coupling reagent was employed to implement a transient protection strategy.
• A one-pot protocol integrated transient protection, activation, aminolysis, and in situ deprotection, avoiding intermediate purification.

Main Results:

• Successfully overcame the long-standing epimerization issue in N→C peptide chain elongation with unprotected amino acids.
• Demonstrated a practical protocol for inverse peptide elongation, enabling efficient synthesis.

Conclusions:

• The developed ynamide coupling method offers a viable and sustainable solution for green peptide synthesis.
• This approach shows potential for synthesizing long peptides and in solid-phase peptide synthesis.