MYRIAPORONES: SYNTHETIC AND BIOLOGICAL STUDIES

小分子天然产物是用于研究蛋白质和细胞功能的一系列有价值的配体。在分子水平上对受体-配体相互作用的详细了解将有助于设计和制备新的化疗药物。具体地说，正在研究一类新的复杂天然产物的构象和生物活性之间的关系。合成能力与高场核磁共振和基于计算机的分子模拟分析相结合，正被用于在分子水平上研究一类新的天然产物的生物活性。一种新的天然产物--myriaporones已被确定为寻找下一代癌症化疗的令人兴奋的领先者。它们的结构与有效的大环内酯类药物tedanolide的结构相似，这导致人们考虑相关的生物学作用模式。介绍了合成桃金娘烯酮1和4的实用路线。还提出了发展新的合成方法，用于立体选择性地生成羟丙酸酯结构单元、烯丙醇和多三取代烯烃。受体分离研究以及母体化合物和类似物的生物活性数据和构象分析将为这些有趣的化合物的分子作用模式提供新的信息。

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.