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Synfacts 2022; 18(12): 1283
DOI: 10.1055/s-0042-1753060
Synthesis of Natural Products

Total Synthesis of (±)-Saxitoxin

Contributor(s):
Erick M. Carreira
,
Henry Lindner
Tanino H, Nakata T, Kaneko T, Kishi Y. * Harvard University, Cambridge, USA
A Stereospecific Total Synthesis of d,l-Saxitoxin.

J. Am. Chem. Soc. 1977;
99: 2818-2819
DOI: 10.1021/ja00450a079.
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Key words

(±)-saxitoxin - paralytic shellfish toxins - Eschenmoser sulfide contraction - Biginelli reaction - Curtius rearrangement - Meerwein's salt

Significance

In 1977, Kishi and co-workers reported the first total synthesis of (±)-saxitoxin in 19 steps. Associated with paralytic shellfish poisoning, the potent neurotoxin was one of the most lethal non-protein substances known. The natural product features three contiguous stereocenters and a remarkably dense collection of heteroatoms with two guanidinium moieties in its tricyclic core.


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Comment

Vinylogous carbamate F was accessed in two steps from thionolactam C via Eschenmoser sulfide contraction. Bignelli reaction with silicon tetraisocyanate and subsequent Curtius rearrangement furnished tricyclic thiourea I. Deprotection of the thioketal and benzyl-ether in four steps from di-guanidine L gave rise to decarbamoylsaxitoxin M. Treatment with chlorosulfonyl isocyanate afforded the natural product.


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Publication History

Article published online:
17 November 2022

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