SYNTHESIS OF MARINE DERIVED MACROCYCLIC SALICYLATES

海洋衍生大环水杨酸盐的合成

• 批准号: 7355164
• 负责人: JEF KAREL DE BRABANDER
• 金额: $ 0.06万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355164
• 关键词: SYNTHESIS; MARINE; DERIVED; MACROCYCLIC; SALICYLATES

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。引起特定生物反应的天然产物代表了识别、研究和靶向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。在此背景下，我们正在开发水杨基卤代酰胺A-B和lobatamides A-F的通用全合成。这些海洋衍生的大环水杨酸酯代表了一个潜在的新的抗肿瘤化合物的机制类，并保证探针试剂的作用机制研究的发展。此外，只有痕量的这些次级代谢产物可以从其天然来源获得，并且这些或任何结构相关的化合物之前都没有合成。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点搜索铺平道路。