SYNTHESIS OF TAXININE AND TAXOL

紫杉烷二萜类化合物由一组植物衍生的天然产物组成。 具有耐人寻味的和重要的生物活性。在他们的 与细胞骨架和组成蛋白的相互作用，几个 紫杉烷在作用于这个细胞系统的分子中是独一无二的 行动方式进一步表现在显著的抗白血病和 该小组的几个成员具有抗肿瘤活性。尤其是紫杉醇 目前正在进行临床试验，可能用作化疗药物 抗癌药物。紫杉烷的天然丰度很低，希望 确定对其生物活性负责的亚结构成分， 结构修饰的紫杉烷可能会证明 在治疗方面的优势，以及它们的有机化学兴趣 复杂的结构使这些物质成为全 综合研究。 本研究的长期目标是开发一种通用的和 紫杉烷的灵活合成，从而提供合成途径 已证实活性的天然物质及其结构类似物。 具体地说，最初的目标将是构建紫杉烷，一种紫杉烷 具有许多与更复杂和更复杂的 具有生物活性的成员。这项工作将在一定程度上模拟最终的 最具化学和生物代表性的紫杉醇的合成 耐人寻味的紫杉烷。最后，制备了对映体纯品 紫杉烷，特别是紫杉醇，将被调查。

The taxane diterpenes comprise a group of plant-derived natural products possessing intriguing and important biological activity. In their interaction with the cytoskeleta and constituent proteins, several of the taxanes are unique among molecules acting on this cellular system and this mode of action further manifests itself in significant anti-leukemic and anti-tumor activity for several members of the group. In particular, taxol is now undergoing clinical trial for possible use as a chemotherapeutic agent against cancer. Low natural abundance of the taxanes, the desire to identify sub-structural elements responsible for their biological activity, the possibility that structurally modified taxanes might prove more advantageous therapeutically, and the organic chemical interest in their complex structures make these substances prime candidates for total synthesis research. The long range goal of the present research is to develop a general and flexible synthesis of the taxanes thereby providing synthetic access to natural substances of proven activity and to their structural analogues. Specifically, the initial objective will be to construct taxinine, a taxane possessing many structural features in common with the more complex and biologically active members. This work will model, in part, the eventual synthesis of taxol, representative of the most chemically and biologically intriguing taxanes. Finally, the preparation of enantiomerically pure taxanes, especially taxol, will be probed.