Biomimetic Peptide Catalytic Bond-Forming Utilizing a Mild Bronsted Acid

Since the global peptide drug market demand has been predicted to increase, highly efficient and inexpensive mass scale peptides are required. However, the production process raises questions about the cost of energy input, scale-up production, raw materials, and solvents treatment. This paper introduces 2 methods for the 2-4 mer oligopeptides bond formation for batch reaction utilizing 50-100 mol% of a mild Bronsted acid under the mild condition. One of the methods has been capably adapted to flow synthesis at room temperature using organic solvents with boiling points below 100 degrees C. The method applies the tert-butoxycarbonyl amino methoxy group, forming the desired dipeptide without solvent at mild temperatures. Furthermore, the conversion of the carboxylic acid leaving the group to phenyl ester promotes peptide bond formation, and the reaction were applied to di, tri, and tetrapeptide bond formation in excellent yield without notable racemization at ambient temperature (up to >99 % yield and 99 : 1 dr). Finally, this study proposes this new production method to overcome the limited scale-up production by reaction device scale: liquid phase biomimetic catalytic peptide flow synthesis utilizing a mild Bronsted acid.

Automated summary

This study introduces two methods for the formation of 2-4 peptide bonds using a mild Bronsted acid under mild conditions. One of the methods has been successfully adapted to flow synthesis at room temperature. This solvent-free method allows for efficient formation of dipeptide, tripeptide, and tetrapeptide bonds at ambient temperature. This study also proposes a new production method to overcome the limitations of scale-up production.