Studies in the Synthesis of Physiologically Important

努力制备具有生物重要性的天然分子对美国的健康科学极其重要。 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培训基地。 其次，这些努力总是提供了一个独特的手段，访问结构活性关系数据的天然产物本身和化合物在类似的结构类别。 第三，这些努力总是导致可用于合成复杂分子的新策略和化学的发展。 本提案介绍了三项此类综合努力。 最成熟的是针对一类角鲨烯合成酶抑制剂，称为phomoidrides。 在这一领域的努力已经产生了新的化学领域的芳基氧化，进一步的发展，在这一领域提出了沿着的第二个合成的努力，直接对ryanodol，一个重要的钙通道阻滞剂。最后，一个富有成效的合作努力，期待在生物学的α，β-环氧酮含天然产物的描述，是注定要提供重要的生物信息的分子在山梨西林类。

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.