MYRIAPORONES: SYNTHETIC AND BIOLOGICAL STUDIES

小分子天然产物是蛋白质和细胞功能研究中有价值的配体集合。在分子水平上对受体-配体相互作用的详细了解将有助于设计和制备新的化疗药物。具体来说，一类新型复杂天然产物的构象与生物活性之间的关系正在研究中。高场核磁共振（NMR）和基于计算机的分子建模分析相结合的合成能力正被用于在分子水平上研究一类新型天然产物的生物活性。一种新的天然产物，多聚腺苷酮，已经被确定为寻找下一代癌症化疗的一个令人兴奋的先导。它们与强效大环内酯丹丹内酯的结构相似，导致人们考虑相关的生物作用模式。介绍了豆蔻酮1和豆蔻酮4的实用合成路线。提出了立体选择性合成羟丙酸结构单元、烯丙醇和聚三取代烯烃的新方法。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了解这些有趣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.