Total synthesis of (-)- and (+)-decarbamoyloxysaxitoxin and (+)-saxitoxin.

Playing the sax: The enantioselective total syntheses of (-)- and (+)-decarbamoyloxysaxitoxin (doSTX) and (+)-saxitoxin (STX) are reported. A new methodology was developed for the synthesis of STXs, featuring discriminative reduction of the nitro group and N-O bond in nitroisoxazolidine. Enantioselective total syntheses of (-)- and (+)-decarbamoyloxysaxitoxin (doSTX) and (+)-saxitoxin (STX) were achieved. The characteristic spiro-fused cyclic guanidine structure of STX was constructed by oxidation at the C4 position with IBX via an alpha-iminium carbonyl intermediate and acid-promoted cyclization of guanidine at the C5 position. A second-generation methodology was developed for the synthesis of STX, featuring discriminative reduction of the nitro group and N-O bond in nitroisoxazolidine. This approach provides efficient access to the key diamine intermediate for STXs.