Synthesis of Carbocyclic and Heterocyclic Compounds (Chemistry)

碳环和杂环化合物的合成（化学）

• 批准号: 8619029
• 负责人: James White
• 金额: $ 35.91万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-15 至 1990-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8619029&HistoricalAwards=false
• 关键词: Synthesis; Carbocyclic; Heterocyclic; Compounds; Chemistry

This research will lead to the development of new synthetic reactions and pathways to some important classes of biologically active alkaloids. It will in addition provide new routes to the important beta-lactams. The synthesis of several carbocyclic and heterocyclic ring systems will be studied with the objective of developing new methodology and applying it to selected targets in the natural product domain. A photochemically mediated cyclization of beta-ketoester enolates will be extended to a system designed to test the feasibility of this reaction in a nine-membered ring, where annulation would afford a tricyclic precursor to the adenylatecyclase inhibitor forskolin. A stannic chloride-mediated cyclization of olefinic beta-ketoesters will also be examined for asymmetric induction where the ester is derived from a chiral alcohol. Application of this technology to synthesis of diterpenes of the stemodane, stemarane, and aphidicolane group is projected. Finally, the cyclization of beta-ketoesters in the presence of manganese acetate will be investigated as a means for elaborating novel bridged frameworks. A route to the taxane family of diterpenoids, specifically taxusin, has been planned around this construct. In the heterocyclic area, a new synthesis of beta.lactams will be pursued that hinges on extrusion of nitrogen from the sulfoximine of a N-aminopyrazolinone with concomitant ring contraction. This methodology will be incorporated into a chiral synthesis of penicillins and other beta-lactam antibiotics. In an extension of work originally carried out by Ghosez, the use of hydrazones of alpha, beta-unsaturated aldehydes in the Diels-Adler reaction will be examined as a device for preparing perhydroisoquinolines. A chiral entry to the gelsemine class of alkaloids, specifically koumine, would be explored by this means.

这项研究将导致新的合成反应的发展 和一些重要的生物活性物质的途径 生物碱此外，它还将为重要的 β-内酰胺 几种碳环和杂环体系的合成 将以开发新方法为目标进行研究， 将其应用于天然产物领域中的选定目标。 一 β-酮酯烯醇化物的光化学介导的环化将 扩展到一个系统，旨在测试这种方法的可行性。 在九元环中的反应，其中成环将提供 腺苷酸环化酶抑制剂佛司可林的三环前体。 一 氯化锡介导烯烃β-酮酯的环化将 也可以检查酯衍生的不对称诱导 从手性醇。 将该技术应用于合成 stemodane、stemarane和aphidicolane组的二萜， 预计。 最后，将β-酮酯在 将研究醋酸锰的存在作为一种手段， 制定新的桥接框架。 一条通往紫杉烷家族的途径 二萜类化合物，特别是紫杉醇，已经围绕这一点进行了规划， 构建体 在杂环化合物领域， 将追求的关键是挤出氮从 具有伴随环的N-氨基吡唑啉酮的磺酰亚胺 收缩。 这种方法将被纳入手性 青霉素和其他β-内酰胺抗生素的合成。 中 最初由Ghosez进行的工作的扩展，使用 α，β-不饱和醛的Diels-Adler腙 反应将被检查作为一种设备，用于制备 全氢异喹啉。 一个手性进入钩吻碱类的 生物碱，特别是钩吻素，将通过这种方法进行研究。