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Divergent Synthesis of Natural Derivatives of (+)‐Saxitoxin Including 11‐Saxitoxinethanoic Acid
Author(s) -
Walker James R.,
Merit Jeffrey E.,
ThomasTran Rhian,
Tang Doris T. Y.,
Du Bois J.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201811717
Subject(s) - saxitoxin , ketene , stille reaction , chemistry , sulfation , stereochemistry , toxin , biochemistry , organic chemistry , catalysis
The bis‐guanidinium toxins are a collection of natural products that display nanomolar potency against select isoforms of eukaryotic voltage‐gated Na + ion channels. We describe a synthetic strategy that enables access to four of these poisons, namely 11‐saxitoxinethanoic acid, C13‐acetoxy saxitoxin, decarbamoyl saxitoxin, and saxitoxin. Highlights of this work include an unusual Mislow–Evans rearrangement and a late‐stage Stille ketene acetal coupling. The IC 50 value of 11‐saxitoxinethanoic acid was measured against rat Na V 1.4, and found to be 17.0 n m , similar to those of the sulfated toxins gonyautoxin II and III.