Total Synthesis of Tetrodotoxin
Keigo Murakami, Tatsuya Toma, Tohru Fukuyama, Satoshi Yokoshima
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.
Topics & Concepts
StereocenterMoietyChemistryCurtius rearrangementTetrodotoxinStereochemistryEnoneNitrileSteric effectsGuanidineTetrahydrofuranAlkyneOrganic chemistrySolventEnantioselective synthesisCatalysisInternal medicineMedicineMarine Toxins and Detection MethodsSynthetic Organic Chemistry MethodsAsymmetric Synthesis and Catalysis