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：关于对映选择性和对映选择性总合成的开发的研究 基于A的实施，Vindoline和临床上重要的抗肿瘤药物葡萄蛋白是详细的 唯一的串联Diels-alder/1,3-二极性环加成级联为1,3,4-氧化唑。除了定义 这种串联环加成级联的范围，在（1）vindorosine的总合成中的应用， （2）Minovine，（3）Aspidospermidine，（4）（ - ） - Vindoline，（5）（+） - Vinblastine和（+） - vincristine，（6）和一个 详细详细介绍了一系列（+） - vinblastine类似物。拟议的研究包括检查 抗肿瘤化合物通过微管蛋白结合介导其细胞作用，并提供良好 在设计，制备和评估基于机制的类似物的设计，准备和评估中定义问题 对负责微管蛋白结合亲和力和选择性的结构特征的基本研究 可以解决。