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的新反应的发展，包括吡啶、四氢呋喃、氨基醇、二醇和二胺。这些分子中有许多具有有用的生物活性，并且/或者是合成更复杂的生物活性分子的重要中间体。例如，天然产物的无机乙酰原家族含有取代的四氢呋喃单元；这类化合物的成员具有广泛的生物活性，包括抗肿瘤、抗疟疾和抗菌。这一分子家族可用于治疗多种疾病，包括癌症和疟疾。取代的吡咯烷类生物碱preussin和大霉素具有有效的抗真菌活性，也具有潜在的抗肿瘤活性。二醇、二胺和氨基醇也存在于大量的生物活性化合物中，包括抗菌剂软膏。

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.