New Methods and Strategies for the Synthesis and Selective Derivatization of Natural Products

项目摘要/摘要 这些研究的重点是开发新的催化方法和战略，以改善 强心类固醇、生物活性萜类和糖基化天然产物分子的可用性 治疗价值。由于类固醇激素对人体重要生物过程的调节作用 在人体内，萜类化合物家族的许多成员都具有广泛的生物学特性 活动。特别是，强心类固醇作为治疗心脏病的有效药物已有数百年的历史。 治疗各种心脏疾病。此外，许多最近的研究表明，这些化合物具有很好的 作为治疗癌症、炎症、免疫和代谢性疾病的潜在药物， 以及各种与健康有关的重要领域，如避孕。这些研究中开发的新技术 合成方法可以显著提高原本难以获得的立体异构体的可用性 具有不寻常的取代或氧化模式的Cardenolide支架，我们的目标之一是进行 多种天然和非天然强心类固醇的药物化学探索。发展起来的技术 该项目还将改善相关天然产品的可及性，如生物活性植物和细菌- 衍生的糖基化类固醇，以及灰色毒素、异海松烷和库拉烷家族的二萜类化合物。最后，这些 研究将产生新的催化技术和策略，使直接和直接的 复杂天然产物的糖基化。这些研究的重要目标之一将是开发 用于不对称反应的新方法和催化剂，使天然产物和 治疗剂。

Project Summary/Abstract These studies are focused on developing new catalytic approaches and strategies to improve the availability of cardiotonic steroids, bioactive terpenoids, and glycosylated natural product-based molecules of therapeutic value. Due to the importance of steroidal hormones for the regulation of vital biological processes in the human body, many members of the terpene family of natural products possess a wide spectrum of biological activities. In particular, cardiotonic steroids have many centuries-long history of serving as effective drugs for the treatment of various heart conditions. In addition, many recent studies suggest that these compounds hold great potential as the therapeutic agents for the treatment of cancer, inflammation, immune and metabolic diseases, and in various important health-related areas such as contraception. The developed in these studies new synthetic approaches could significantly improve the availability of otherwise difficult-to-access stereoisomeric cardenolide scaffolds with unusual substitution or oxidation patterns, and one of our objectives is to conduct the medicinal chemistry exploration of various natural and unnatural cardiotonic steroids. The techniques developed in this project will also improve the accessibility of related natural products such as bioactive plant- and bacteria- derived glycosylated steroids, and diterpenes of grayanotoxin, isopimarane and kuarane families. Finally, these studies will result in new catalytic techniques and strategies that will enable a direct and straightforward glycosylation of complex natural products. One of the important objectives of these studies will be developing new methods and catalysts for the asymmetric reactions that will enable the synthesis of natural products and therapeutic agents.