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.
Iwamoto
Osamu
O
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Shinohara
Ryoko
R
Nagasawa
Kazuo
K
D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C076433:decarbamoyloxysaxitoxin; D012530:Saxitoxin