The Chemistry and Biology of the Tetrodotoxin Natural Product Family

B Benedikt Nißl (Department of Pharmacy Ludwig‐Maximilians‐Universität München Butenandtstr. 5–13, Haus C 81377 Munich Germany) M Marcel Mülbaier (Drug Discovery Engine Grünenthal GmbH Zieglerstr. 6 52078 Aachen Germany) F Francesca Grisoni (Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven AI Systems Institute 1 , Eindhoven,) D Dirk Trauner (P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry) M Marcel Bermúdez C Clemens Dialer (Drug Discovery Engine Grünenthal GmbH Zieglerstr. 6 52078 Aachen Germany) D David B. Konrad

Abstract

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.

Article Details

Volume / Issue Vol. 64, Issue 35
Published August 25, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (7)

B

Benedikt Nißl

Department of Pharmacy Ludwig‐Maximilians‐Universität München Butenandtstr. 5–13, Haus C 81377 Munich Germany

M

Marcel Mülbaier

Drug Discovery Engine Grünenthal GmbH Zieglerstr. 6 52078 Aachen Germany

F

Francesca Grisoni

Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven AI Systems Institute 1 , Eindhoven,

D

Dirk Trauner

P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry

M

Marcel Bermúdez

C

Clemens Dialer

Drug Discovery Engine Grünenthal GmbH Zieglerstr. 6 52078 Aachen Germany

D

David B. Konrad