PYRROLE BASED APPROACH TO RIGIDIN AND RELATED ALKALOIDS

描述：首席调查员指出，近年来他已经 积极参与开发高效和区域可控的合成方法 含有吡咯的物质，其后经生物测试为 国家癌症研究所的体外筛查计划的一部分 这些合成方法是基于缩合反应的 含α-氨基甲酰化合物的乙烯基亚胺盐衍生物。他 表明作为这个节目的一部分，他目前正在执导他的 努力开发一种新的、新颖的海洋衍生生物碱，里吉丁 已被证明是钙调蛋白激活的重要抑制物 磷酸二酯酶，一个可能的化疗靶点。在这项提议中，他 声明，他寻求至少完成四件事：1.扩大 他为区域控制的制剂而发展的化学 二取代吡咯与三取代吡咯的合成。2. 进行适当的实验以了解控制特性 多种葡萄糖类化合物中三取代吡咯的形成 亚胺盐衍生物。3.开始将这种化学应用于 新型钙调蛋白拮抗剂Rigidin及其相关物质的合成 如具有生物活性的天然产物聚柠檬酮A。继续 提交里吉丁和多聚柠檬酮A类似物、前体和相关样品 含有吡咯的化合物送到NCI进行进一步的生物学评价 体外部分，初步的抗肿瘤筛查计划。

DESCRIPTION: The principal investigator notes that in recent years he has been actively involved in developing efficient and regiocontrolled syntheses for pyrrole containing substances which have subsequently been bioassayed as part of the National Cancer Institute's in vitro screening program and that these synthetic methods have been based on the condensation reactions of vinylogous iminium salt derivatives with alpha-aminocarbonyl compounds. He indicates that as part of this program, he is currently directing his efforts towards a new and novel, marine derived alkaloid, Rigidin which has been shown to be a significant inhibitor of Calmodulin activated phosphodiesterase, a possible chemotherapeutic target. In this proposal he states that he seeks to accomplish at least four things: 1. extend the chemistry that he has developed for the regiocontrolled preparation of disubstituted pyrroles to the synthesis of trisubstituted pyrroles. 2. carry out appropriate experiments to understand the controlling features for the formation of trisubstituted pyrroles from a variety of vinylogous iminium salt derivatives. 3. to begin to apply this chemistry to the synthesis of the novel, Calmodulin antagonist Rigidin and related substances such as the bioactive, natural product Polycitone A. 4. to continue to submit samples of Rigidin and Polycitone A analogs, precursors and related pyrrole containing compounds to the NCI for further biological evaluation as part of the in vitro, primary antitumor screening program.