GENERAL METHODS FOR SYNTHESIS OF BIOACTIVE HETEROCYCLES

本申请中描述的研究的长期目标是 开发新的立体控制方法来合成各种 不饱和杂环系统。 绝大多数的药物 在医学实践中是杂环。 我们相信通过开发高效的 杂环系统的合成条目，我们将允许有前途的 医药先导未来发展迅速潜力巨大 治疗意义 杂环化反应是我们提出的研究重点， 04至07年项目。 这种类型的环化反应 比相应的由多烯制备碳环化合物更先进 循环 我们将继续关注杂环化反应 其由乙烯基硅烷封端。 自从我们引进这些 在1980年的环化终止剂中，乙烯基硅烷已被证明可用于 许多实验室终止各种各样的环化 反应. 由于新发起人计划在 扩大杂环化化学的视野，我们还旨在 开发新的氮杂环和氧杂环化引发剂。 与帕金森氏病刺激物相关的四氢吡啶，MPTP， 会做好准备。 新的抗生素链唑啉将在 对映体选择性形式，以及强大的“子宫排空”二萜 佐帕他诺。 中间体和天然产物的目标将被广泛地 壳牌生物科学研究中心的生物活性 开发公司，在NCI。

The long-term objective of the research described in this application is to develop new stereocontrolled methods for the synthesis of a variety of unsaturated heterocyclic systems. The vast majority of pharaceuticals used in medical practice are heterocycles. We believe by developing efficient synthetic entries to heterocyclic ring systems, we will allow promising pharacological leads in the future to be rapidly developed with potential therapeutic implications. Heterocyclization reactions are the focus of the studies we propose for the 04 to 07 project years. Cyclizations of this type are much less well developed than the corresponding preparation of carbocycles by polyene cyclizations. Our attention will continue to focus on heterocyclizations which are terminated by vinylsilanes. Since our introduction of these cyclization terminators in 1980, vinylsilanes have proven useful in a number of laboratories to terminate a wide variety of cyclization reactions. Because of the pivotal role that new initiators plan in expanding the horizons of heterocyclization chemistry, we also aim to develop new azacyclic and oxacyclic cyclization initiators. Tetrahydropridines related to the Parkinson's disease stimulaten, MPTP, will be prepared. The new antibiotic streptazolin will be prepared in enantioselective form, as will the powerful "uteroevacuant" diterpene zoapatanol. Intermediates and natural product targets will be broadly sdcrened for biological activity at the Biological Sciences Research Center of the Shell Development Co., and at NCI.