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
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.
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.
