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

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.

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