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Total Synthesis of Tetrodotoxin
Author(s) -
Murakami Keigo,
Toma Tatsuya,
Fukuyama Tohru,
Yokoshima Satoshi
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201916611
Subject(s) - moiety , stereocenter , chemistry , tetrodotoxin , curtius rearrangement , stereochemistry , guanidine , steric effects , nitrile , enone , tetrahydrofuran , alkyne , combinatorial chemistry , organic chemistry , solvent , enantioselective synthesis , biology , catalysis , biophysics
Abstract A total synthesis of tetrodotoxin was accomplished. A Diels–Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which was used to construct the remaining stereogenic centers. A nitrogen atom was introduced either by a four‐step sequence involving a Curtius rearrangement, or a three‐step sequence featuring a newly developed transformation of a terminal alkyne into a nitrile. Introduction of the guanidine moiety followed by the formation of the heterocyclic system by cascade reactions led to tetrodotoxin.