Vindoline and Vinblastine

描述（由申请人提供）：基于1，3，4-恶二唑的独特串联Diels-Alder/1，3-偶极环加成级联的实施，详细描述了文多林和临床重要抗肿瘤药物长春碱的非对映选择性和对映选择性全合成的开发研究。除了定义这种串联环加成级联的范围外，还详细介绍了（1）长春新碱，（2）米诺文，（3）aspidospermidine，（4）（-）-vindoline，（5）（+）-长春碱和（+）-长春新碱，（6）和广泛系列的（+）-长春碱类似物的全合成中的应用。拟议的研究包括检查的抗肿瘤化合物，介导其细胞的影响，通过微管蛋白结合，并提供了一个明确的问题的设计，制备和评价的合成，机制为基础的类似物，其中负责微管蛋白结合亲和力和选择性的结构特征的基础研究可能会得到解决。

DESCRIPTION (provided by applicant): 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.