SYNTHESIS OF TAXININE AND TAXOL

紫杉碱和紫杉醇的合成

• 批准号: 3181749
• 负责人: CHARLES S SWINDELL
• 金额: $ 8.27万
• 依托单位: BRYN MAWR COLLEGE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1989-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3181749
• 关键词: alkaloids; antileukemic agent; antineoplastics; chemical structure function; diterpenes; drug /agent; drug design /synthesis /production; medicinal plants; paclitaxel; plant extracts; stereochemistry

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.

紫杉烷二萜类化合物是一类植物源性天然产物 具有有趣而重要的生物活性。 在他们 与胞浆素和组成蛋白的相互作用， 紫杉烷类在作用于该细胞系统的分子中是独特的，并且这 其作用方式进一步表现为显著的抗白血病和 抗肿瘤活性。 特别是紫杉醇 目前正在进行临床试验，可能用作化疗药物 抗癌剂。 低天然丰度的紫杉烷， 确定负责其生物活性亚结构元件， 结构修饰的紫杉烷可能会证明更多的可能性， 在治疗上有利，以及其有机化学兴趣 复杂的结构使这些物质成为总 综合研究 本研究的长期目标是开发一个通用的， 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。 具体来说，最初的目标将是构建紫杉宁，一种紫杉烷 具有许多结构特征， 生物活性分子。 这项工作将部分模拟最终的 紫杉醇的合成，最具化学和生物学意义的 有趣的紫杉烷类 最后，制备对映体纯的 将对紫杉烷类，特别是紫杉醇进行研究。