Vindoline and Vinblastine

文多林和长春花碱

• 批准号: 7766953
• 负责人: DALE L BOGER
• 金额: $ 32.66万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-10 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766953
• 关键词: Address; Affinity; Alder plant; Alkaloids; Binding; Binding Sites; Biological; Biological Factors; Clinical; Colchicine; Coupled; Development; Diels Alder reaction; Drug Delivery Systems; Electrons; Ensure; Evaluation; Mediating; Modification; Oxadiazoles; Paclitaxel; Pharmaceutical Preparations; Preparation; Roentgen Rays; Secure; Series; Source; Structure; Technology; Tubulin; Vinblastine; Vincristine; Vindoline; abstracting; analog; antitumor drug; aspidospermidine; base; cancer therapy; cost; cycloaddition; design; dimer; improved; minovine; protein protein interaction

Abstract: Studies on the development of a diastereoselective and enantioselective total synthesis of vindoline and the clinically important antitumor drug vinblastine are detailed based on implementation of a unique tandem Diels-Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles. In addition to defining the scope of such tandem cycloaddition cascades, applications in the total synthesis of (1) vindorosine, (2) minovine, (3) aspidospermidine, (4) (-)-vindoline, (5) (+)-vinblastine and (+)-vincristine, (6) and an extensive series of (+)-vinblastine analogues are detailed. The proposed studies include the examination of antitumor compounds that mediate their cellular effects through tubulin binding and provide a well- defined problem on the design, preparation, and evaluation of synthetic, mechanism-based analogues in which fundamental studies of the structural features responsible for tubulin binding affinity and selectivity may be addressed.

摘要：研究了一种非对映选择性和对映选择性的全合成方法， 文多林和临床上重要的抗肿瘤药物长春碱是详细的基础上实施的一个 1，3，4-恶二唑的独特串联Diels-Alder/1，3-偶极环加成级联。除了定义 这种串联环加成级联的范围，在（1）长春新碱， (2)米诺维碱，（3）aspidospermidine，（4）（-）-vindoline，（5）（+）-长春碱和（+）-长春新碱，（6）和 详述了广泛系列的（+）-长春碱类似物。拟议的研究包括审查 的抗肿瘤化合物，通过微管蛋白结合介导其细胞效应，并提供良好的- 定义的问题，设计，制备和评价的合成，机制为基础的类似物， 其中对影响微管蛋白结合亲和力和选择性的结构特征进行了基础研究 可以解决。