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Total Synthesis of 11‐Saxitoxinethanoic Acid and Evaluation of its Inhibitory Activity on Voltage‐Gated Sodium Channels
Author(s) -
Wang Chao,
Oki Mana,
Nishikawa Toru,
Harada Daisuke,
YotsuYamashita Mari,
Nagasawa Kazuo
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201604155
Subject(s) - chemistry , aldol condensation , total synthesis , marine toxin , stereochemistry , tetrodotoxin , aldol reaction , sodium , reagent , biochemistry , toxin , organic chemistry , catalysis , medicine
Abstract 11‐Saxitoxinethanoic acid (SEA) is a member of the saxitoxin (STX) family of paralytic shellfish poisons, and contains an unusual C−C bond at the C11 position. Reported herein is a total synthesis of SEA. The key to our synthesis lies in a Mukaiyama aldol condensation reaction of silyl enol ether with glyoxylate in the presence of an anhydrous fluoride reagent, [Bu 4 N][Ph 3 SnF 2 ], which directly constructs the crucial C−C bond at the C11 position in SEA. The Na V Ch‐inhibitory activities of SEA and its derivatives were evaluated by means of cell‐based assay. SEA showed an IC 50 value of (47±12) n m , which is approximately twice as potent as decarbamoyl‐STX (dcSTX).