Peptide Bond-Forming Reaction via Amino Acid Silyl Esters: New Catalytic Reactivity of an Aminosilane
Wataru Muramatsu, Chaitanya Manthena, Erika Nakashima, Hisashi Yamamoto
Abstract
The epimerization-free formation of peptide bonds is crucial for the development of peptide therapeutics and pharmaceuticals. Herein, we report a hydrosilane-mediated approach for the construction of peptide bonds between most amino acids under ambient conditions. This concise protocol with an original silylating reagent HSi(OCH(CF3)2)3 facilitates the use of amino acids bearing a broad variety of functional groups without any epimerization. Moreover, a catalytic system using an aminosilane catalyst enables not only the acceleration in silylation of carboxylic acids but also amide synthesis with minimal substrate use (electrophile/nucleophile/silylating reagent = 1:1:1) and waste production (hydrogen gas and a siloxane). These simple and powerful approaches are established as a potentially general paradigm in synthesis of desired peptides in high yields.