SYNTHETIC APPROACH TO THE DITERPENE INGENOL

二萜巨大戟二萜醇的合成方法

• 批准号: 6179098
• 负责人: NAEEM YUSUFF
• 金额: $ 2.77万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6179098
• 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.

本提案将研究高应变二萜烯醇的合成。ingenol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。鉴于这些化合物具有有趣的活性，因此非常需要合成衍生物来建立构效关系，这可能最终导致治疗化合物的开发。虽然已经有相当多的合成努力，但尚未完成全合成。其关键的合成特征是BC环接合处的“内、外”或反桥头立体化学。闭合环复合反应（RCM）是一种构造多种环烯烃的有效方法，可应用于这种应变体系的构造。将进行实验，以确定闭合环复合方法是否可以首先应用于ingenol环系统的模型，然后用于ingenol的全合成。