MYRIAPORONES: SYNTHETIC AND BIOLOGICAL STUDIES

多菌酮：合成和生物学研究

• 批准号: 6045906
• 负责人: Richard E. Taylor
• 金额: $ 20.39万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6045906
• 关键词: antineoplastic antibiotics; biological products; conformation; drug design /synthesis /production; macrolide antibiotics; pharmacokinetics; receptor binding; stereochemistry

Small molecule natural products represent a valuable collection of ligands for use in the study of protein and cellular function. A detailed understanding of receptor-ligand interactions at the molecular level will allow for the design and preparation of new chemotherapeutic agents. Specifically, the relationship between conformation and biological activity of a novel class of complex natural products is being investigated. The power of synthesis in combination with high field nuclear magnetic resonance (NMR) and computer-based molecular modeling analysis is being used to investigate the biological activity of a novel class of natural product at the molecular level. A new class of natural product, myriaporones, has been identified as an exciting lead in the search for the next generation of cancer chemotherapy. Their structural similarity to the potent macrolide tedanolide leads one to consider a related biological mode of action. Practical synthetic routes to myriaporone 1 and myriaporone 4 are presented. The development of new synthetic methodology for the stereoselective creation of hydroxypropionate structural units, allylic alcohols, and poly-trisubstituted olefins is also proposed. Receptor isolation studies as well as biological activity data and conformational analysis of the parent compounds and analogues will provide new information about the details about the molecular mode of action of these interesting compounds.

小分子天然产物代表了用于蛋白质和细胞功能研究的有价值的配体集合。在分子水平上对受体-配体相互作用的详细理解将允许设计和制备新的化疗药物。 具体而言，一类新的复杂天然产物的构象和生物活性之间的关系正在研究中。 合成的力量结合高场核磁共振（NMR）和基于计算机的分子建模分析正在被用来研究一类新的天然产物在分子水平上的生物活性。 一类新的天然产物，myriaporones，已被确定为一个令人兴奋的领导在寻找下一代癌症化疗。 它们与强效大环内酯类化合物tedanaltine的结构相似性使人们考虑相关的生物学作用模式。 介绍了myriaporone 1和myriaporone 4的实用合成路线。 还提出了立体选择性地生成羟基丙酸酯结构单元、烯丙醇和多三取代烯烃的新合成方法的发展。 受体分离研究以及生物活性数据和母体化合物和类似物的构象分析将提供关于这些有趣化合物的分子作用模式的细节的新信息。