Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin

Shigeki Tsuchiya, Yuko Cho, Renpei Yoshioka, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Saxitoxin (STX) and its analogues are potent voltage-gated sodium channel blockers biosynthesized by freshwater cyanobacteria and marine dinoflagellates. We previously identified genetically predicted biosynthetic intermediates of STX at early stages, Int-A′ and Int-C′2, in these microorganisms. However, the mechanism to form the tricyclic skeleton of STX was unknown. To solve this problem, we screened for unidentified intermediates by analyzing the results from previous incorporation experiments with 15N-labeled Int-C′2. The presence of monohydroxy-Int-C′2 and possibly Int-E′ was suggested, and 11-hydroxy-Int-C′2 and Int-E′ were identified from synthesized standards and LC-MS. Furthermore, we observed that the hydroxy group at C11 of 11-hydroxy-Int-C′2 was slowly replaced by CD3O in CD3OD. Based on this characteristic reactivity, we propose a possible mechanism to form the tricyclic skeleton of STX via a bicyclic intermediate from 11-hydroxy-Int-C′2.

Original languageEnglish
Pages (from-to)5327-5331
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number19
DOIs
Publication statusPublished - 2017 May 2

Keywords

  • biosynthesis
  • mass spectrometry
  • natural products
  • reaction mechanisms
  • saxitoxin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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