Non-catalytic low-cost and sustainable amidation using a twisted amide

Area of Science:

• Organic Chemistry
• Sustainable Chemistry

Background:

• Amide synthesis faces challenges in cost reduction and environmental impact.
• Developing sustainable and economical synthetic routes is crucial for chemical manufacturing.

Purpose of the Study:

• To establish a cost-effective and environmentally friendly method for amide synthesis.
• To explore the application of this method in peptide and peptoid synthesis.

Main Methods:

• Conversion of carboxylic acids to amides via a twisted amide intermediate using tosyl isocyanate and bromoacetate.
• Reaction of the twisted amide with amines to yield amides and tosylglycine esters.
• Demonstration of epimerization-suppressed amidation, column chromatography-free synthesis, and solid-phase synthesis.

Main Results:

• Successful synthesis of amides and valuable tosylglycine esters from carboxylic acids.
• Established epimerization-suppressed amidation and chromatography-free/solid-phase synthesis protocols.
• Demonstrated sustainable peptoid synthesis utilizing the co-product tosylglycine ester.

Conclusions:

• The developed method offers a practical solution to cost and sustainability issues in amide synthesis.
• This approach provides a versatile platform for peptide and peptoid synthesis with reduced environmental impact.
• The effective utilization of co-products enhances the overall sustainability of the process.