Novel Routes to Cyclic Peptide Cytochalasin Analogs

环肽细胞松弛素类似物的新途径

• 批准号: 6863642
• 负责人: JOEL D MOORE
• 金额: $ 4.4万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-16 至 2006-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6863642
• 关键词: cyclic peptides; cytochalasins; peptide analog; peptide chemical synthesis; postdoctoral investigator; synthetic peptide

DESCRIPTION (provided by applicant): The proposed research centers around the syntheses of an array of cyclic peptide cytochalasin analogs exploiting a novel, diastereoselective, silicon-tethered Diels-Alder cycloaddition toward the construction of the isoindolone core unit prevalent in this family of natural products. The facile approach to the cytochalasin skeleton provides the base for cytochalasin library synthesis. To prove the efficacy of this methodology, the core scaffold will initially be manipulated toward the known bioactive agent, cytochalasin B. It will be the ultimate goal of this research to utilize the core structure toward the production of novel cyclic peptide cytochalasin analogs using a diversity oriented approach. The molecules produced have the ability to serve as probes into cytochalasin-cell membrane interactions as well as have potential as biologically important compounds in areas such as cancer and AIDS research. This method also displays synthetic convergence, as a myriad of cytochalasin scaffolds can be generated from a single core unit. Finally, this research is amenable to the solid phase, which will be exploited in a cytochalasin library synthesis utilizing a ring-closing olefin metathesis cyclorelease strategy.

描述（由申请人提供）：所提出的研究中心围绕环状肽细胞松弛素类似物的阵列的合成，该环状肽细胞松弛素类似物利用新型的非对映选择性的硅系狄尔斯-阿尔德环加成来构建该天然产物家族中普遍存在的异吲哚酮核心单元。细胞松弛素骨架的简易方法为细胞松弛素文库的合成提供了基础。为了证明这种方法的有效性，首先将核心支架朝向已知的生物活性剂细胞松弛素B进行操作。本研究的最终目标是利用核心结构，采用多样性导向的方法生产新型环肽细胞松弛素类似物。所产生的分子具有作为细胞松弛素-细胞膜相互作用的探针的能力，并且具有在诸如癌症和艾滋病研究等领域中作为生物学重要化合物的潜力。该方法还显示合成收敛，因为可以从单个核心单元产生无数的细胞松弛素支架。最后，这项研究是服从固相，这将是利用在细胞松弛素库合成利用环烯烃复分解环释放策略。