Isostearyl Mixed Anhydrides for the Preparation of -Methylated Peptides Using -Terminally Unprotected -Methylamino Acids

Sustainable and efficient manufacturing methods for -methylated peptides remain underexplored despite growing interest in therapeutic -methylated peptides within the pharmaceutical industry. A methodology for the coupling of -terminally unprotected -methylamino acids mediated by an isostearic acid halide (ISTAX) and silylating reagent has been developed. This approach allows for the coupling of a wide variety of amino acids and peptides in high yields under mild conditions without the need for a -terminal deprotection step in the process of -terminal elongation. These advantages make this a useful synthetic method for the production of peptide therapeutics and diagnostics containing -methylamino acids.