Fishlock Dan, Williams Robert M
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
J Org Chem. 2008 Dec 19;73(24):9594-600. doi: 10.1021/jo801159k.
A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.
本文描述了强效抗癌药物Et-743的正式全合成。使用乙二醛亚胺的新型自由基环化反应立体选择性地构建了四氢异喹啉核心。对该核心的进一步修饰能够快速得到Et-743的五环核心，但在关键的Pictet-Spengler环合反应中得到了区域异构体的混合物。截获了Et-743合成中一个已知的高级中间体，完成了该分子的形式合成。
