Cyclic Guanidine Compounds from Toxic Newts Support the Hypothesis that Tetrodotoxin is Derived from a Monoterpene

Yuta Kudo, Takeshi Yasumoto, Dietrich Mebs, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The biosynthesis of tetrodotoxin (TTX), a potent neurotoxin consisting of a 2,4-dioxaadamantane skeleton and a guanidine moiety, is an unsolved problem in natural product chemistry. Recently, the first C5–C10 directly bonded TTX analogue, 4,9-anhydro-10-hemiketal-5-deoxyTTX, was obtained from toxic newts and its carbon skeleton suggested a possible monoterpene origin. On the basis of this hypothesis, screening of predicted biosynthetic intermediates of TTX was performed using two MS-guided methods. Herein, five novel cyclic guanidine compounds from toxic newts are reported which commonly contain a cis-fused bicyclic structure including a six-membered cyclic guanidine. These structures could be biosynthetically derived from geranyl guanidine through oxidation, cyclization, and/or isomerization steps. LC–MS analysis confirmed the widespread distribution of the five novel compounds in toxic newt species. These results support the hypothesis that TTX is derived from a monoterpene.

Original languageEnglish
Pages (from-to)8728-8731
Number of pages4
JournalAngewandte Chemie - International Edition
Volume55
Issue number30
DOIs
Publication statusPublished - 2016 Jul 18

Keywords

  • biosynthesis
  • mass spectrometry
  • natural products
  • structure elucidation
  • tetrodotoxin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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