THE SYNTHESIS OF SOME COMPLEX CYTOTOXIC COMPOUNDS

一些复杂细胞毒性化合物的合成

• 批准号: 3168198
• 负责人: RICHARD H SCHLESSINGER
• 金额: $ 9.63万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168198
• 关键词: Fungi; antineoplastic antibiotics; drug design /synthesis /production; plant extracts

It is our intention to accomplish the following synthetic goals within the time frame requested for this grant application. Firstly, we intend to complete, as proposed, the total synthesis of vertisporin, a potent cytotoxic drug which belongs to the roridin family of antibiotics. Vertisporin is probably the most complex member of this class of compounds, and contains, among other functionality, a 16-membered bislactone ring which is itself unusual. Vertisporin in available is submilligram amounts, and as a result, we have assembled intermediates in sufficient quantity to allow us to prepre up to 2.0 grams of the natural product. Secondly, we are intending to embark on the total synthesis of a very new natural product, sesbanimide. Apparently, only a very few milligrams of this substance are available, since the isolation method required to obtain this substance is arduous in the extreme. Because sesbanimide is described as an extremely potent cytotoxic material, clearly in short supply, and most interestingly possessed of a novel and unusual structure, we have designed a 10-step synthetic construction of the molecule. The projected synthesis has, in part, been quided by a series of computer calculations which represents a new departure for this group. The synthesis of sesbanimide starts from a readily available sugar, and on the assumption that a viable synthesis scheme is developed, it should be possible to prepare large quantities of this most interesting natural product. Both vertisporin and sesbanimide will be submitted to the CCNS for testing.

我们打算在联合国系统内实现下列综合目标： 此资助申请所需的时间范围。 首先，我们打算完成，如建议的那样， vertisporin是一种强效细胞毒性药物，属于罗里丁家族， 抗生素 轮孢菌素可能是该类中最复杂的成员 的化合物，并含有，除其他功能，16元 bislactone环which哪一个is itself本身un寻常. 可用的Vertisporin是 亚毫克的量，因此，我们已经组装了中间体， 足够的数量，使我们能够prepre高达2.0克的天然 产品 第二，我们打算着手全面综合一个非常新的 天然产物，田菁亚胺。 很明显，只有极少量的 这种物质是可用的，因为获得所需的分离方法 这种物质是极其艰苦的。 因为田菁亚胺被描述为 作为一种非常有效的细胞毒性材料，显然供应短缺， 最有趣的是拥有一个新颖和不寻常的结构，我们有 设计了一个10步合成的分子结构。 预计 合成部分是由一系列计算机计算完成的 这代表了这个群体的一个新的起点。 的合成 sesbanimide从容易获得的糖开始，并且假设 如果开发出可行的合成方案， 准备大量的这种最有趣的天然产品。 vertisporin和sesbanimide都将提交给CCNS进行检测。