Studies in the Synthesis of Physiologically Important

在美国，努力制备具有重要生物学意义的自然分子对健康科学是非常有价值的。首先，这些努力为开发下一代重要药物的科学家提供了一个特殊的训练基地。其次，这些努力总是为获取天然产物本身和类似结构类化合物的结构活性关系数据提供了一种独特的方法。第三，这些努力总是导致新的策略和化学的发展，可用于复杂分子的合成。本建议描述了三种这样的综合努力。最成熟的是针对一类角鲨烯合成酶抑制剂，称为磷酰化物。在这一领域的努力催生了芳基氧化领域的新化学；在这一领域的进一步发展，并提出了第二个合成努力，直接对红烷醇，一种重要的钙通道阻滞剂。最后，一项富有成效的合作努力正在研究含有α， β -环氧酮的天然产物的生物学，注定要提供关于山梨比西林类分子的重要生物学信息。

Efforts to prepare naturally occurring molecules of biological importance are extremely valuable to health sciences in the United States. Firstly, these efforts provide an exceptional training ground for scientist who will develop the next generation of important drugs. Second, these efforts always provide a unique means of accessing structure activity relationship data for the natural products themselves and compounds in similar structural classes. Thirdly, these efforts always result in the development of new strategies and chemistry that can be used for the synthesis of complex molecules. This proposal describes three such synthetic efforts. The most mature is directed toward a class of squalene synthase inhibitors known as the phomoidrides. Efforts in this area have spawned new chemistry in the field of aryl oxidation; further developments in this area are proposed along with a second synthetic effort directed toward ryanodol, an important calcium channel blocker. Finally, a fruitful collaborative effort looking at the biology of alpha, beta-epoxy ketone-containing natural products is described that is destined to provide important biological information about molecules in the sorbicillin class.