3 years ago

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

Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin
Yasukatsu Oshima, Renpei Yoshioka, Mari Yotsu-Yamashita, Shigeki Tsuchiya, Keiichi Konoki, Kazuo Nagasawa, Yuko Cho
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. Skeleton key: Intermediates in early stages of the biosynthesis of saxitoxin have been identified through a combination of LC-MS and synthesis. Incorporation experiments with 15N-labeled compounds have shown that these previously proposed intermediates are key precursors of the potent voltage-gated sodium channel blocker. A mechanism for the formation of the tricyclic skeleton of saxitoxin is also put forward.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201612461

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.