权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
10557215
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.

项目总结/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、生物活性萜类化合物和糖基化天然产物基分子的可用性治疗价值由于甾体激素对调节体内重要生物过程的重要性，人体，天然产物的萜烯家族的许多成员具有广谱的生物活性，活动特别是，强心剂类固醇作为有效药物已有数百年的历史。治疗各种心脏病。此外，最近的许多研究表明，这些化合物具有很大的作为治疗癌症、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。在这些研究中开发的新合成方法可以显着提高否则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cardenoprotein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，衍生的糖基化甾族化合物，以及grayanotoxin、isopimarane和kuarane家族的二萜。最后这些研究将导致新的催化技术和战略，这将使直接和简单的复杂天然产物的糖基化。这些研究的一个重要目标是开发用于不对称反应的新方法和催化剂，这将使天然产物的合成成为可能，治疗剂。