SYNTHETIC APPROACH TO THE DITERPENE INGENOL

这项建议将研究高应变二萜吲哚的合成。吲哚类化合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构效关系，这最终可能导致治疗性化合物的发展。虽然已经有相当多的合成努力来合成吲哚酚，但还没有完成完全的合成。吲哚酚的关键合成特征是BC环结的紧张的“内、外”或跨桥头立体化学。闭环歧化反应(RCM)已成为合成各种环烯烃的有效方法，并可应用于构建这一应变体系。将进行实验，以确定闭环复分解方法是否可以首先应用于吲哚环体系的模型，然后用于吲哚全合成。

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.