New Reactions for Heterocycle Synthesis

描述(由申请人提供)：本建议书描述了可用于制备重要类别的化合物的新反应的发展，这些化合物包括吡咯烷、四氢呋喃、氨基醇、二醇和二胺。其中许多分子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，天然产物番荔枝内酯家族含有取代的四氢呋喃单元；这类化合物的成员表现出广泛的生物活性，包括抗肿瘤、抗疟疾和抗微生物。这一分子家族可能有助于治疗包括癌症和疟疾在内的各种疾病。取代的吡咯烷生物碱普鲁辛和山奈霉素具有很强的抗真菌活性，同时也显示出潜在的抗肿瘤活性。二元醇、二胺和氨基醇也存在于大量的生物活性化合物中，包括抗菌剂Discodermolide。 与目前合成上述化合物的现有方法相比，本提案中描述的新反应具有许多显著的优点。所提出的反应的起始原料简单且容易获得，并且这些反应在一个过程中形成了几个不同的键和多个立体中心。这些新反应对环境无害，并将提供更短的路线到达上述分子，这将使重要的药物化合物更容易获得，成本低于当前技术所允许的水平。这些新的程序还将允许合成有趣的、具有生物活性的分子的新衍生品，这可能导致发现新的药物和疾病治疗方法。

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.