Vindoline and Vinblastine

文摘：非对映选择性和对映体选择性全合成的研究进展 长春花碱和临床上重要的抗肿瘤药物长春花碱在一项 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 这种串联环加成反应的范围，在(1)长春花碱全合成中的应用， (4)(-)长春花碱、(5)()-长春花碱和()-长春新碱，(6)和 详细介绍了()-长春花碱类似物的广泛系列。建议的研究包括考试 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- 关于合成的、基于机理的类似物的设计、制备和评估的明确问题 对微管蛋白结合亲和力和选择性负责的结构特征的基础研究 可能会被解决。

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.