Synthesis of Pederin Hybrids for Biological Evaluation

用于生物学评价的 Pederin 杂种的合成

• 批准号: 7154711
• 负责人: JAIME A MUELLER
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7154711
• 关键词: affinity chromatography; analog; binding proteins; biological products; cell line; chemical addition; cytotoxicity; family; neoplasm /cancer; protein binding; pyrans

DESCRIPTION (provided by applicant): This research proposal describes the convergent synthetic designs for psymberin and several structural hybrids to determine the structural origin of the unique, selective, highly potent cytotoxicity exhibited by this pederin natural product. The specific design of the structural hybrids will test whether the top acyclic side chain and central pyran core are the essential features and determine a simplified, easily accessable analogue for development. The enantioselective hetero-Diels-Alder cycloaddition is the key transformation for rapid generation of either highly substituted gem-dimethyl pyran core featured in the pederin family with the desired lower side chain intact. Biological evaluation of psymberin and the structural hybrids is proposed against several tumor cell lines. In addition, the protein binding partner(s) of psymberin and the structural hybrids will be determined by affinity chromatography.

描述（由申请人提供）：本研究计划描述了 psymberin 和几种结构杂合体的趋同合成设计，以确定这种 pederin 天然产物所表现出的独特、选择性、高效细胞毒性的结构起源。结构杂化物的具体设计将测试顶部无环侧链和中央吡喃核心是否是基本特征，并确定一个简化的、易于开发的类似物。对映选择性杂狄尔斯-阿尔德环加成是快速生成佩德林家族中高度取代的偕二甲基吡喃核心的关键转化，且所需的下侧链完整。提出了针对几种肿瘤细胞系对薄荷素及其结构杂交体进行生物学评价。此外，将通过亲和层析测定 psymberin 和结构杂合体的蛋白质结合配偶体。