SYNTHESIS OF MARINE DERIVED MACROCYCLIC SALICYLATES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。引发特定生物反应的天然产物代表了识别、研究和瞄准可能的新基因产物的独特工具。该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物的设计和合成。在这种情况下，我们正在开发水杨基哈拉酰胺a - b和洛巴塔酰胺a - f的多功能全合成。这些海洋衍生的大环水杨酸盐是一类潜在的新型抗肿瘤化合物，是研究其作用机制的探针试剂。此外，这些次生代谢物只能从它们的天然来源中获得微量的，而且这些以及任何结构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先导优化工作和基于亲和力的天然产物生物靶标搜索铺平道路。

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.