Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin
| Autor: | Yasukatsu Oshima, Keiichi Konoki, Renpei Yoshioka, Yuko Cho, Mari Yotsu-Yamashita, Kazuo Nagasawa, Shigeki Tsuchiya |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyanobacteria Stereochemistry viruses Molecular Conformation 010402 general chemistry 01 natural sciences Catalysis 03 medical and health sciences chemistry.chemical_compound Reactivity (chemistry) Voltage-Gated Sodium Channel Blockers Saxitoxin chemistry.chemical_classification biology Bicyclic molecule 010405 organic chemistry Hydroxy group General Medicine General Chemistry respiratory system biochemical phenomena metabolism and nutrition biology.organism_classification Skeleton (computer programming) 0104 chemical sciences 030104 developmental biology chemistry Dinoflagellida bacteria Tricyclic |
| Zdroj: | Angewandte Chemie International Edition. 56:5327-5331 |
| ISSN: | 1433-7851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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