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

该项目将针对苯并[1，2-B：3，4-b ']的合成 二吡咯衍生物。 这些材料之所以引起人们的兴趣，是因为 具有抗肿瘤活性的抗生素（CC-1065 NCS）的发现 298223），其由三个取代的苯并[1，2-：3，4-b '] 二吡咯环。 苯并[1，2-B：2，4-b ']二吡咯的四种合成方法 概述了系统。 这些方法包括使用方法学的直接合成 改编自吲哚化学，通过吡咯的二聚化合成， 通过环化-芳构化合成和通过硫化物挤出合成。 具体的起始材料和程序进行了讨论，为每一个 综合办法。 用于偶联所述三个亚基的方法 CC-1065结构通过形成酰胺键。 的 讨论了CC-1065类似物的合成方法的推广。 设计用于探测某些结构元件作用的特定类似物 给出了 这些建议特别强调， CC-1065作用机制中的环丙烷环。 合成 将对材料进行评估，以确定合作的可行性 与国家癌症治疗部药物开发分支 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.