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Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin
Author(s) -
Tsuchiya Shigeki,
Cho Yuko,
Yoshioka Renpei,
Konoki Keiichi,
Nagasawa Kazuo,
Oshima Yasukatsu,
YotsuYamashita Mari
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201612461
Subject(s) - tricyclic , chemistry , int , stereochemistry , bicyclic molecule , total synthesis , saxitoxin , biosynthesis , skeleton (computer programming) , biochemistry , biology , toxin , enzyme , anatomy , computer science , operating system
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 15 N‐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 CD 3 O in CD 3 OD. 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.