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Efficient Synthesis of Biologically Active Peptides Based on Micro-flow Amide Bond Formation

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Middle Molecular Strategy

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Abstract

Peptide drugs have garnered much attention in recent years because they possess the merits of both protein drugs and small-molecule-based drugs. In particular, specialty peptides such as N-methylated peptides and cyclic peptides have become increasingly important as drug candidates. Developing an inexpensive process for peptide chain elongation, that would also be high-yielding and scalable, however, is a highly challenging task even under the most promising reported conditions. We have performed amidations using highly active, high-atom economy, and inexpensive coupling agents. These highly active agents accelerated both the desired and the side reactions. The undesired reactions were suppressed, however, by taking advantage of micro-flow technology that allows precise control of both the reaction time and the temperature. Here we introduce our originally developed amidations for use with biologically active peptides including highly racemizable peptides, cyclic peptides, and bulky N-methylated peptides.

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Authors and Affiliations

  1. Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan

    Shinichiro Fuse

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Correspondence to Shinichiro Fuse .

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Editors and Affiliations

  1. Graduate School of Science, Osaka University, Toyanaka, Osaka, Japan

    Koichi Fukase

  2. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Takayuki Doi

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Fuse, S. (2021). Efficient Synthesis of Biologically Active Peptides Based on Micro-flow Amide Bond Formation. In: Fukase, K., Doi, T. (eds) Middle Molecular Strategy. Springer, Singapore. https://doi.org/10.1007/978-981-16-2458-2_9

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