SYNTHESIS OF MARINE DERIVED MACROCYCLIC SALICYLATES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。引起特定生物反应的天然产物是识别、研究和瞄准可能的新基因产物的独特工具。这项研究计划的一部分是针对对哺乳动物细胞具有独特作用的天然产品的设计和合成。在此背景下，我们正在开发一种多用途的水杨基卤胺A-B和洛巴胺A-F的全合成方法。这些海洋衍生的大环水杨酸酯代表了一类潜在的新的抗肿瘤化合物的机制，并为开发用于作用机制研究的探针试剂奠定了基础。此外，这些次生代谢物只能从它们的自然来源中获得微量，而且这些化合物或任何结构上相关的化合物以前都没有合成过。化学合成和细胞分析之间的积极相互作用将为铅的优化努力和基于亲和力的天然产物生物靶标的搜索铺平道路。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Natural products that elicit a specific biological response represent unique tools to identify, study, and target possible new gene products. Part of this research program is directed towards the design and synthesis of natural products that have unique actions on mammalian cells. In this context, we are developing a versatile total synthesis of salicylhalamides A-B and lobatamides A-F. These marine-derived macrocyclic salicylates represent a potentially new mechanistic class of antitumor compounds, and warrant the development of probe reagents for mechanism of action studies. In addition, only trace quantities of these secondary metabolites can be obtained from their natural source and neither these, nor any structurally related compounds, have been synthesized previously. An active interplay between chemical synthesis and cellular assays will pave the way for lead optimization efforts and an affinity-based search for the natural product's biological target.