Abstract

Micro-Flow Synthesis of Amino Acid N-Carboxy Anhydrides and Their Derivatization via pH Flash Switching and Rapid Dual Activation

Shinichiro Fuse, Professor, Nagoya University

Amino Acid N-Carboxy Anhydrides (NCAs) are important as monomers in polypeptide synthesis. The most conventional synthetic approach for NCAs uses strong acidic conditions. Therefore, NCAs containing acid-labile functional groups cannot be prepared. On the other hand, NCAs canbe rapidly generated under basic conditions, however, they rapidly occur overreactions under the basic conditions. We developed and used pH flash switching technology in a micro-flow reactor. Acid-labile NCAs were successfully prepared by our developed approach. We also demonstrated derivatization of labile NCAs using rapid dual activation of both NCAs and electrophiles in a micro-flow reactor.