BENZO (1 2 - B:4 3 - B') DIPYRROLE DERIVATIVES SYNTHESIS

该项目将用于苯并[1，2-b：3，4-b‘]的合成。 联吡咯的衍生物。这些材料已经成为人们感兴趣的材料，因为 一种具有抗肿瘤活性抗生素(CC-1065 NCS)的发现 298223)，由三个取代苯并[1，2-：3，4-b‘]构成 联吡咯环。苯并[1，2-b：2，4-b‘]联吡咯的四种合成方法 对系统进行了概述。其中包括使用方法学进行直接合成。 改编自吲哚化学，通过吡咯的二聚化合成， 环化-芳构化合成和硫化物挤出合成。 具体的开始材料和程序讨论了每一个 人工合成方法。的三个子单元的耦合方法。 指出了CC-1065的结构是通过形成酰胺键来实现的。这个 讨论了该合成方法对CC-1065类似物的推广。 为探索某些结构元素的作用而设计的特定模拟 提出了一种新的解决方案。这些都特别强调了 环丙烷环在CC-1065中的作用机理。合成材料 将在合作中评估材料的抗肿瘤活性 与国家癌症治疗司药物开发处合作 卫生研究院。

The project will be directed toward the synthesis of benzo[1,2-b:3,4-b'] dipyrrole derivatives. These materials have become of interest because of the discovery of an antibiotic with anti-tumor activity (CC-1065 NCS 298223) which is constructed from three substituted benzo[1,2-:3,4-b'] dipyrrole rings. Four general approaches to benzo[1,2-b:2,4-b'] dipyrrole systems are outlined. These include direct synthesis using methodology adapted from indole chemistry, synthesis by dimerization of pyrroles, synthesis by cyclization-aromatization and synthesis by sulfide extrusion. Specific starting materials and procedures are discussed for each of the synthetic approaches. Methods for coupling the three subunits of the CC-1065 structure by formation of amide bonds are indicated. The generalization of the synthetic method to analogs of CC-1065 is discussed. Specific analogs designed to probe the role of certain structural elements are presented. These particularly emphasize the possible role of the cyclopropane ring in the mechanism of action of CC-1065. The synthetic materials will be evaluated for antineoplastic activity in collaboration with the Drug Development Branch, Division of Cancer Treatment, National Institutes of Health.