New Reactions for Heterocycle Synthesis

杂环合成的新反应

基本信息

批准号：
7391054
负责人：
JOHN P WOLFE
金额：
$ 22.78万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2010-03-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal describes the development of new reactions that can be used for the preparation of important classes of compounds including pyrrolidines, tetrahydrofurans, amino alcohols, diols, and diamines. Many of these molecules possess useful biological activity, and/or are important intermediates in the synthesis of more complex biologically active molecules. For example, the annonaceous acetogenin family of natural products contain substituted tetrahydrofuran units; members of this class of compounds exhibit a wide range of biological activities including antitumor, antimalarial, and antimicrobial. This family of molecules could be useful for the treatment of a variety of diseases including cancer and malaria. The substituted pyrrolidine alkaloids preussin and anisomycin have potent antifungal activity and also exhibit potentially useful antitumor activity. Diols, diamines, and amino alcohols are also found in a large number of biologically active compounds including the antibacterial agent discodermolide. The new reactions described in this proposal have a number of significant advantages over currently available methods for the synthesis of the compounds described above. The starting materials for the proposed reactions are simple and readily available, and the reactions lead to the formation of several different bonds and multiple stereocenters in single process. These new reactions are environmentally benign and will provide much shorter routes to the molecules described above, which will make important medicinal compounds more readily available at a lower cost than current technology allows. These new procedures will also allow for the synthesis of new derivatives of interesting, biologically active molecules which may lead to the discovery of new medicines and treatments for disease.

描述（由申请人提供）：该提案描述了可用于制备重要化合物类别的新反应的开发，包括吡咯烷、四氢呋喃、氨基醇、二醇和二胺。这些分子中的许多具有有用的生物活性，和/或是合成更复杂的生物活性分子的重要中间体。例如，天然产物的番荔枝苷家族含有取代的四氢呋喃单元；此类化合物的成员表现出广泛的生物活性，包括抗肿瘤、抗疟疾和抗菌。该分子家族可用于治疗包括癌症和疟疾在内的多种疾病。取代的吡咯烷生物碱普鲁士素和茴香霉素具有有效的抗真菌活性，并且还表现出潜在有用的抗肿瘤活性。二醇、二胺和氨基醇也存在于大量生物活性化合物中，包括抗菌剂 discodermolide。该提案中描述的新反应与目前可用的合成上述化合物的方法相比具有许多显着的优点。所提出的反应的起始材料简单且容易获得，并且反应导致在单一过程中形成几种不同的键和多个立构中心。这些新反应对环境无害，并将为上述分子提供更短的路径，这将使重要的药物化合物更容易以比现有技术允许的成本更低的成本获得。这些新程序还将允许合成有趣的生物活性分子的新衍生物，这可能会导致新药物和疾病治疗方法的发现。