Accepted Articles e202502404
Review
Open Access

The Chemistry and Biology of the Tetrodotoxin Natural Product Family

Benedikt Nißl

Benedikt Nißl

Ludwig-Maximilians-Universitat Munchen, Pharmacy, Butenandtstr. 5-13, AK Konrad, 81377 München, GERMANY

Search for more papers by this author
Marcel Mülbaier

Marcel Mülbaier

Grünenthal GMBH: Gruenenthal GmbH, Drug Discovery Engine, Zieglerstr. 6, 52078 Aachen, GERMANY

Search for more papers by this author
Francesca Grisoni

Francesca Grisoni

Eindhoven University of Technology: Technische Universiteit Eindhoven, Biomedical Engineering Department, Groene Loper 3, Eindhoven, NETHERLANDS, KINGDOM OF THE

Search for more papers by this author
Dirk Trauner

Dirk Trauner

University of Pennsylvania, Department of Chemistry, 231 South 34th Street, 19104-6323 Philadelphia, UNITED STATES OF AMERICA

Search for more papers by this author
Marcel Bermúdez

Marcel Bermúdez

University of Munster: Westfalische Wilhelms-Universitat Munster, Institute for Pharmaceutical and Medicinal Chemistry, Corrensstr. 48, 48149 Münster, GERMANY

Search for more papers by this author
Clemens Dialer

Clemens Dialer

Grünenthal GMBH: Gruenenthal GmbH, Drug Discovery Engine, Zieglerstr. 6, 52078 Aachen, GERMANY

Search for more papers by this author
David B. Konrad

Corresponding Author

David B. Konrad

Ludwig-Maximilians-Universität München: Ludwig-Maximilians-Universitat Munchen, Pharmacy, Butenandtstr. 5-13, AK Konrad, 81377 München, GERMANY

Search for more papers by this author
First published: 18 June 2025

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.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.