Premium
Diverted Total Synthesis and Biological Evaluation of Gambierol Analogues: Elucidation of Crucial Structural Elements for Potent Toxicity
Author(s) -
Fuwa Haruhiko,
Kainuma Noriko,
Tachibana Kazuo,
Tsukano Chihiro,
Satake Masayuki,
Sasaki Makoto
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400355
Subject(s) - ciguatoxin , stereochemistry , ether , chemistry , marine toxin , ciguatera , dinoflagellate , structure–activity relationship , biological activity , toxicity , side chain , toxin , in vitro , biology , biochemistry , organic chemistry , fish <actinopterygii> , botany , fishery , polymer
Gambierol is a polycyclic ether toxin, which has been isolated from the marine dinoflagellate Gambierdiscus toxicus . A series of gambierol analogues have been prepared from an advanced intermediate of our total synthesis of gambierol and investigated for their toxicity against mice, thus providing the first systematic structure–activity relationships (SAR) of this polycyclic ether class of marine toxin. The SAR studies described herein clearly indicate that 1) the C28C29 double bond within the H ring and the unsaturated side chain are the crucial structural elements required for exerting potent biological activity and 2) the C1 and C6 hydroxy groups, the C30 methyl group, and the C37C38 double bond have little influence on the degree of neurotoxicity against mice.