Fleming James J, Du Bois J
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2006 Mar 29;128(12):3926-7. doi: 10.1021/ja0608545.
An asymmetric synthesis of the bis-guanidinium poison, (+)-saxitoxin (STX), is described. Commencing from an N,O-acetal starting material made readily available through sulfamate ester C-H amination, the completed route to STX showcases the utility of oxathiazinane dioxide heterocycles for the assembly of polyfunctionalized amine derivatives. In the final preparative stages, an unusual nine-membered ring guanidine intermediate is oxidized selectively and made to undergo dehydrative cyclization to afford the tricyclic core of the natural product. Access to STX and related structures will provide unique pharmacological tools for the study of voltage-regulated Na+ ion channel proteins.
描述了双胍类毒素（+）-石房蛤毒素（STX）的不对称合成。从通过氨基磺酸酯C-H胺化容易获得的N，O-乙缩醛起始原料开始，完成的STX合成路线展示了二氧化氧杂噻嗪烷杂环在多官能化胺衍生物组装中的效用。在最后的制备阶段，一种不寻常的九元环胍中间体被选择性氧化并进行脱水环化，以提供天然产物的三环核心。获得STX及相关结构将为研究电压调节的Na+离子通道蛋白提供独特的药理学工具。
