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
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.
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.
