New Reactions for Heterocycle Synthesis

描述（由申请人提供）：本提案描述了可用于制备重要类别化合物（包括吡咯烷、四氢呋喃、氨基醇、二醇和二胺）的新反应的开发。这些分子中的许多具有有用的生物活性，和/或在合成更复杂的生物活性分子中是重要的中间体。例如，番荔枝内酯家族的天然产物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。这个分子家族可以用于治疗各种疾病，包括癌症和疟疾。取代的吡咯烷生物碱普鲁辛和茴香霉素具有有效的抗真菌活性，也显示出潜在的有用的抗肿瘤活性。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。 本提案中描述的新反应与目前可获得的用于合成上述化合物的方法相比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，并且反应导致在单个过程中形成几个不同的键和多个立体中心。 这些新的反应对环境无害，并将为上述分子提供更短的路线，这将使重要的药用化合物更容易以比现有技术更低的成本获得。 这些新方法还将允许合成有趣的生物活性分子的新衍生物，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.