# Straightforward, scalable, solution-phase synthesis of peptide bonds in flow

## TL;DR

Researchers developed a scalable method for making peptides using flow chemistry, enabling efficient synthesis of bioactive peptides.

## Contribution

A new solution-phase flow method for scalable peptide synthesis using in-situ activation as mixed anhydrides.

## Key findings

- Diverse dipeptides were successfully prepared in plug flow.
- Continuous flow conditions enabled gram-scale synthesis of a hexapeptide precursor.
- The method was validated with the synthesis of a bioactive cyclic peptide precursor.

## Abstract

We report the development of simple solution-phase flow conditions for the scalable synthesis of peptides using in-situ activation as mixed anhydrides, contributing to the synthetic toolbox of available solution-phase flow reactions. This approach has been used for the preparation of a series of diverse dipeptides in plug flow, and then continuous flow conditions (< 10 mmol) were developed and applied to the gram scale synthesis of the hexapeptide linear precursor for the bioactive cyclic peptide segetalin A as further proof of the utility of this approach.

The online version contains supplementary material available at 10.1007/s41981-025-00347-2.