SYNTHETIC APPROACH TO THE DITERPENE INGENOL

二萜巨大戟二萜醇的合成方法

• 批准号: 2865268
• 负责人: NAEEM YUSUFF
• 金额: $ 3.03万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2865268
• 关键词: alkenes; antiAIDS agent; antineoplastics; cyclization; diterpenes; drug design /synthesis /production; stereochemistry

This proposal will investigate the synthesis of the highly strained diterpene ingenol. Derivatives of ingenol posses a wide array of biological activity, including anti-tumor, tumor-promoting, and anti-HIV activity. Given the interesting activity of these compounds, there is a great need for synthetic derivatives to establish structure-activity relationships, which may ultimately lead to the development of therapeutic compounds. Although there has been considerable synthetic effort towards ingenol, a total synthesis has not been completed. The critical synthetic feature of the ingenol is the strained "inside, outside" or trans intrabridgehead stereochemistry of the BC ring juncture. The ring closing metathesis (RCM) reaction has emerged as a powerful method for the construction of a variety of cyclic olefins and may be applied to the construction of this strained system. Experiments will be conducted to determine if the ring closing metathesis methodology can be applied first to models of the ingenol ring system, and then towards a total synthesis of ingenol.

该提案将研究高度紧张的二萜巨大戟二萜醇的合成。 巨大戟二萜醇衍生物具有广泛的生物活性，包括抗肿瘤、促肿瘤和抗 HIV 活性。 鉴于这些化合物的有趣活性，非常需要合成衍生物来建立结构-活性关系，这可能最终导致治疗化合物的开发。尽管对巨大戟二萜醇的合成做出了相当大的努力，但全合成尚未完成。 巨大戟二萜醇的关键合成特征是BC环连接处的应变“内部、外部”或反式桥头内立体化学。 闭环复分解（RCM）反应已成为构建各种环烯烃的有力方法，并且可以应用于这种应变系统的构建。 将进行实验以确定闭环复分解方法是否可以首先应用于巨大戟二萜醇环系统的模型，然后应用于巨大戟二萜醇的全合成。