The Chemistry and Biology of the Tetrodotoxin Natural Product Family

Benedikt Nißl; Marcel Mülbaier; Francesca Grisoni; Dirk Trauner; Marcel Bermúdez; Clemens Dialer; David B. Konrad

doi:10.1002/anie.202502404

The Chemistry and Biology of the Tetrodotoxin Natural Product Family

Benedikt Nißl
, Marcel Mülbaier
, Francesca Grisoni
, Dirk Trauner
, Marcel Bermúdez
, Clemens Dialer (Corresponding author)
, David B. Konrad (Corresponding author)

Research output: Contribution to journal › Review article › peer-review

4 Citations (Scopus)

Abstract

Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemists due to its exceptional polarity, complex architecture, and important biological activity. This review highlights the diversity of the tetrodotoxin natural product family and discusses the origins of derivatives, biosynthetic hypotheses, and biological activities. Furthermore, potential therapeutic applications and structure–activity relationship studies are covered, along with the total syntheses of the natural product and selected derivatives that were published to date.

Original language	English
Article number	e202502404
Number of pages	32
Journal	Angewandte Chemie - International Edition
Volume	64
Issue number	35
DOIs	https://doi.org/10.1002/anie.202502404
Publication status	Published - 25 Aug 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 14 Life Below Water

Keywords

Chemical probes
Medicinal chemistry
Nociception
Total synthesis
Voltage-gated sodium channels

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10.1002/anie.202502404

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Cite this

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abstract = "Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemists due to its exceptional polarity, complex architecture, and important biological activity. This review highlights the diversity of the tetrodotoxin natural product family and discusses the origins of derivatives, biosynthetic hypotheses, and biological activities. Furthermore, potential therapeutic applications and structure–activity relationship studies are covered, along with the total syntheses of the natural product and selected derivatives that were published to date.",

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AU - Nißl, Benedikt

AU - Mülbaier, Marcel

AU - Grisoni, Francesca

AU - Trauner, Dirk

AU - Bermúdez, Marcel

AU - Dialer, Clemens

AU - Konrad, David B.

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KW - Chemical probes

KW - Medicinal chemistry

KW - Nociception

KW - Total synthesis

KW - Voltage-gated sodium channels

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AN - SCOPUS:105012138719

SN - 1433-7851

VL - 64

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 35

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ER -

The Chemistry and Biology of the Tetrodotoxin Natural Product Family

Abstract

Bibliographical note

UN SDGs

Keywords

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