具有重要生理活性海洋环肽酯Lagunamide、Apratoxins及其氟代类似物的合成和活性评价研究

项目名称： 具有重要生理活性海洋环肽酯Lagunamide、Apratoxins及其氟代类似物的合成和活性评价研究

项目编号： No.21272041

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 魏邦国

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 本项目以合成方法和生物活性评价为导向，开展具有重要生理活性Lagunamide和Apratoxins类中四个海洋环肽酯及其氟代类似物合成和活性评价研究，其中，海洋环肽酯Lagunamide A、Apratoxins D、E为首次全合成。本项目具体拟开展基于廉价樟脑为辅基诱导的高位阻手性亚磺酰胺的合成方法学研究；基于Strecker、加成、交叉偶联和新迁移等反应，开展手性高位阻亚磺酰胺辅基诱导的氟代氨基酸制备方法学研究；开展具有抗白血病、抗肿瘤活性的海洋环肽酯Lagunamide A和Apratoxins D、E首次全合成研究；开展Lagunamide A、Apratoxins A，D、E含氟类似物的合成和活性评价研究。本项目的开展不仅对复杂化合物的多样性合成做出基础性贡献，而且为进一步开展海洋天然产物Lagunamide和Apratoxins类化合物的药理学研究奠定基础。

中文关键词： 天然产物；海洋环肽；多样性合成；Lagunamides；Apratoxin

英文摘要： This project will be focused on the syntheses of four marine natural products (lagunamide A and apratoxins A, D, E) and their fluorinated structural analogues. Due to their important anti- cancer/leukemia activities, our major efforts will be on the first asymmetric total syntheses of lagunamide A, apratoxins D and E, followed by construction of a small molecular library with natural-product-like structural and biological diversity. In this project, we will conduct the following research: (1) Explore a new method to synthesize highly steric chiral sulfinamide auxiliaries starting from cheap (+) or (-)- camphor, and apply them in imine-based asymmetric reactions; (2) Explore new synthetic methods to prepare fluorinated amino acid derivatives using asymmetric Strecker, cross-coupling and migration reactions; (3) Investigate first total syntheses of lagunamide A, apratoxins D and E; (4) Synthesize a series of fluorinated analogues of lagunamide A, apratoxins A, D and E; (5) Study the structure-activity relationship (SAR) of the synthetic natural products and new fluorinated analogues. The above systematic research around the marine natural products will provide novel synthetic methodologies to produce fluorinated amino acids derivatives, and new synthetic strategies to construct our well-designed macrocycle librar

英文关键词： Natural Products；Marine Cyclic Depsipeptide；Divergent Synthesis；Lagunamides；Apratoxin