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Synfacts 2020; 16(03): 0261
DOI: 10.1055/s-0039-1691679
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (±)-Tetrodotoxin

Contributor(s):
Erick M. Carreira
,
Michael A. Imhof
Kishi Y. * Fukuyama T, Aratani M, Nakatsubo F, Goto T, Inoue S, Tanino H, Sugiura S, Kakoi H. Harvard University, Cambridge, USA
Synthetic Studies on Tetrodotoxin and Related Compounds. IV. Stereospecific Total Syntheses of dl-Tetrodotoxin.

J. Am. Chem. Soc. 1972;
94: 9219-9221
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Further Information

Publication History

Publication Date:
18 February 2020 (online)

 
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Key words

(±)-tetrodotoxin - Diels–Alder cycloaddition - Beckmann rearrangement - Baeyer–Villiger oxidation

Significance

In 1972, Kishi and co-workers disclosed the first total synthesis of (±)-tetrodo­toxin, a potent neurotoxin commonly associated with sea food poisoning. Tetrodotoxin has found application in medicinal chemistry as analgesic treatment option in cancer therapy. Kishi describes the complete total synthesis in a series of four publications; the one presented here and J. Am. Chem. Soc. 1972, 94, 9217, Tetrahedron Lett. 1970, 11, 5129, and Tetra­hedron Lett. 1970, 11, 5127.


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Comment

D was accessed by Diels–Alder reaction of B with butadiene (C). Subsequent Beckmann rearrangement of D allowed access to acetamide E, which underwent epoxidation and in situ ether-bridge formation. Conversion of K into L was enabled by Bayer–Villiger oxidation followed by lactone cleavage and in situ epoxide opening.


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