Synfacts 2019; 15(02): 0109
DOI: 10.1055/s-0037-1611971
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Saxitoxin and 11-Saxitoxinethanoic Acid

Erick M. Carreira
Felix Pultar
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;
DOI: 10.1002/anie.201811717.
Further Information

Publication History

Publication Date:
18 January 2019 (online)



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.



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.