2012 Volume 70 Issue 11 Pages 1178-1186
Saxitoxin is as potent and specific blocker of voltage-gated sodium channels as tetrodotoxin. This unique biological activity has established the importance of these two small natural products in neurophysiological experiments. In order to find new blockers of the voltage-gated sodium channels, an efficient synthetic route to the skeleton of saxitoxin was developed. This new synthetic route is based on two key reactions (i) cascade cyclization of a guanidino-acetylene initiated by the bromocation (Br+) and (ii) transformation of the geminal-dibromomethylene moiety to enol acetate, and culminated in the total synthesis of decarbamoyl-α-saxitoxinol, a naturally-occurring analog of saxitoxin.