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DOI: 10.1055/s-0043-1774904
Total Synthesis of (+)-Saxitoxin
A Synthesis of (+)-Saxitoxin.
J. Am. Chem. Soc. 2006;
128: 3926-3927
DOI: 10.1021/ja0608545.
Key words
(+)-saxitoxin - (β)-saxitoxinol - C–H activation - zinc-acetylide addition - Lindlar hydrogenation - Staudinger reduction - alkene ketohydroxylation
Significance
In 2006, Du Bois and Fleming presented the enantioselective synthesis of (+)-saxitoxin, a paralytic agent isolated from oceanic red tides. The bioactivity of (+)-saxitoxin derives from the selective blockage of cations through Na+ ion channels. It is a highly attractive target for total synthesis due to its tricyclic structure decorated with nitrogen and oxygen atoms.
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Comment
The synthesis commences with the preparation of cyclic sulfamate D via Rh-catalyzed C–H activation followed by nucleophilic addition of the preformed zinc-acetylide species to N,O-acetal A. AgNO3 initiates guanidine formation to form the nine-membered heterocycle K as a key intermediate. Alkene ketohydroxylation of K triggers the transannular cyclization to the 5/6 fused bicyclic structure M. From there, (β)-saxitoxinol and (+)-saxitoxin are accessed.
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Publikationsverlauf
Artikel online veröffentlicht:
14. Juni 2024
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