Synthesis of (+)-Saxitoxin

Key words

medium-sized ring formation - ketohydroxylation -

Significance

(+)-Saxitoxin is a paralytic agent from oceanic red tides. It blocks cationic influx through voltage-dependent Na⁺ channels. Notable features of the synthesis include formation of a medium-sized guanidine ring from a carbodiimide and regio- and stereoselective oxidation of alkene C to hydroxyketone D.

Comment

Reduction of azide A and immediate treatment with AgNO₃ and Et₃N generated N-sulfonylcarbodiimide B which reacted with the C6 amine to form a nine-membered ring. Carbamate C was regioselectively oxidized to hydroxyketone D which underwent nucleophilic addition to generate bicyclic E as a single stereoisomer. When OsO₄ was used in the transformation of C to D, the regioisomeric α-hydroxyketone was obtained.