A micro-flow rapid dual activation approach for urethane-protected α-amino acid N-carboxyanhydride synthesis

Abstract

A variety of urethane-protected α-amino acid N-carboxyanhydrides (UNCAs) were synthesized in high yields via the rapid dual activation of both an α-NCA and alkyl chloroformate by combination of two amines in a micro-flow reactor.

Facile Generation of tert-Butoxycarbonyl Chloride Equivalent and Its Use in Microflow Reactor

“…The attack of 1 on 6 may also generate BocX 8 . We speculated that the generated electrophiles 6 and 8 were unstable and underwent decomposition, such as decarboxylation and/or dealkylation . Therefore, the observed combined yields of 4 and 5 were less than 70%.…”

Recent Advances in the Solid- and Solution-Phase Synthesis of Peptides and Proteins Using Microflow Technology

“…Fuse et al reported microflow peptide syntheses via the generation of highly active electrophiles and synthesized natural products using the developed method. , They recently reported the microflow synthesis of urethane-protected α-amino acid N -carboxyanhydride (UNCA) 17 by rapid dual activation of both alkyl chloroformate 14 and α-NCA 15 . They demonstrated a high-yielding one-flow synthesis of the two α-dipeptides 19 and 20 using the highly electrophilic UNCA (Figure ).…”

Rapid and column-chromatography-free peptide chain elongation via a one-flow, three-component coupling approach

“…16 We reported a micro-flow peptide chain elongation using highly electrophilic species, 17 as well as a one-step micro-flow synthesis of NCAs 18 and the derivatizations. 19 Herein, we report an efficient peptide chain elongation based on a one-flow, 3CC approach using α-NCA J (Scheme 1e). Although all the previously reported α-NCA-based approaches used α-NCA only as an electrophile (Scheme 1d), our approach is the first to use α-NCA J as both a nucleophile and an electrophile.…”