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，详细介绍了开发非对映选择性和对映选择性长春花碱和临床上重要的抗肿瘤药物长春花碱全合成的研究。除了定义这种串联环加成反应的范围外，还详细介绍了在(1)长春花碱、(2)米诺文、(3)阿司匹林、(4)(-)-长春花碱、(5)(+)-长春花碱和(+)-长春新碱、(6)和一系列(+)-长春花碱类似物的全合成中的应用。拟议的研究包括通过微管蛋白结合来调节其细胞效应的抗肿瘤化合物的检查，并为合成的、基于机制的类似物的设计、制备和评估提供了一个明确的问题，其中可能涉及对微管蛋白结合亲和力和选择性的结构特征的基础研究。

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.