Walker JR,
Merit JE,
Thomas-Tran R,
Tang DT. Y,
Du Bois J.
* Stanford University, USA
Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid.
Angew. Chem. Int. Ed. 2019;
Key words
(+)-saxitoxin - saxitoxinethanoic acid - Evans–Mislow rearrangement - Liebeskind–Stille–Migita coupling
Significance
The authors report the total syntheses of (+)-saxitoxin and several structural analogues including saxitoxinethanoic acid. These bis-guanidinium natural products have been of high interest due to their extraordinary activity against voltage-gated sodium ion channels.
Comment
Electrophilic aromatic substitution and rhodium-catalyzed oxidative cyclization yield tricyclic system E from simple starting materials. Clever application of an Evans–Mislow rearrangement gives access to advanced intermediate F that is used to complete the synthesis of both target structures.
