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

天然产物合成和选择性衍生化的新方法和新策略

基本信息

批准号：
10369654
负责人：
Pavel Nagorny
金额：
$ 35.67万
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：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-01-31
项目状态：
未结题

项目摘要

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.

项目概要/摘要这些研究的重点是开发新的催化方法和策略，以改善强心类固醇、生物活性萜类化合物和糖基化天然产物分子的可用性治疗价值。由于甾体激素对于调节重要生物过程的重要性在人体中，萜烯家族天然产物的许多成员都具有广谱的生物活性活动。特别是，强心类固醇作为治疗心脏疾病的有效药物已有数百年的历史。治疗各种心脏病。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、免疫和代谢疾病的治疗剂的潜力，以及避孕等各种重要的健康相关领域。这些研究中开发的新合成方法可以显着提高原本难以获得的立体异构体的可用性具有不寻常取代或氧化模式的心烯内酯支架，我们的目标之一是进行各种天然和非天然强心类固醇的药物化学探索。开发的技术该项目还将提高相关天然产品的可及性，例如生物活性植物和细菌- 衍生的糖基化类固醇，以及灰木毒素、异海葵烷和瓜烷家族的二萜。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发展不对称反应的新方法和催化剂，将能够合成天然产物和治疗剂。