Single-Step, Rapid, and Mild Synthesis of β-Amino Acid N-Carboxy Anhydrides Using Micro-Flow Technology.
Naoto SugisawaYuma OtakeHiroyuki NakamuraShinichiro FusePublished in: Chemistry, an Asian journal (2019)
β-Amino acid N-carboxy anhydrides (β-NCAs) are rarely used in the synthesis of β-peptides, which is due mainly to the poor availability of these potentially useful substrates. Herein, we describe the heretofore challenging synthesis of β-NCAs via a single-step, rapid, and mild formation using pH flash switching and flash dilution, which are aspects of micro-flow technology. We synthesized 15 β-NCAs in good to excellent yields that included acid-labile β-NCAs that cannot be readily synthesized using the conventional Leuchs approach. Scaled-up synthesis using this process can be readily achieved via continuous operation.