Related Experiment Video
Updated: Dec 9, 2025

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
Structures of N-Hydroxy-Type Tetrodotoxin Analogues and Bicyclic Guanidinium Compounds Found in Toxic Newts
Yuta Kudo1,2, Charles T Hanifin3, Yuichi Kotaki4
1Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Abstract:
The biosynthesis of tetrodotoxin (TTX, 1), a potent neurotoxin widely distributed in marine and terrestrial metazoans, remains unresolved. A significant issue has been identifying intermediates and shunt products associated with the biosynthetic pathway of TTX. We investigated TTX biosynthesis by screening and identifying new TTX-related compounds from Cynops ensicauda popei and Taricha granulosa. Mass spectrometry (MS)-guided screening identified two new N-hydroxy TTX analogues in newts: 1-hydroxy-8-epiTTX (2) and 1-hydroxy-8-epi-5,11-dideoxyTTX (3, previously reported as 1-hydroxy-5,11-dideoxyTTX). We prepared a new analogue, 8-epi-5,11-dideoxyTTX (4), from 3 via N-OH reduction and confirmed the presence of 4 in T. granulosa using hydrophilic interaction liquid chromatography (HILIC)-LCMS. The presence of 8-epi-type TTX analogues in both Cynops and Taricha supports a branched biosynthetic pathway of terrestrial TTX, which produces 6- and 8-epimers. In addition, new bicyclic guanidinium compounds Tgr-238 (5) and Tgr-240 (6) were identified as putative shunt products of our proposed TTX biosynthesis pathway. A structural analysis of Cep-228A (7), another bicyclic compound, was performed using NMR. Based on the structures of 5-7 and their analogues, we propose a model of the shunt and metabolic pathways of the terrestrial TTX biosynthesis.
More Related Videos
11:04Unraveling the Role of Discrete Areas of the Rat Brain in the Regulation of Ovulation through Reversible Inactivation by Tetrodotoxin Microinjections
Published on: September 3, 2020
09:45Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Related Concept Videos
Physical Properties of Amines
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
Antidotes
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
Types of Toxins
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...