FURAN-CARBONYL PHOTOCYCLOADDITIONS IN ORGANIC SYNTHESIS

有机合成中的呋喃-羰基光环负载

• 批准号: 3281452
• 负责人: STUART L SCHREIBER
• 金额: $ 13.57万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281452
• 关键词: alkaloids; antiarthritic agent; antiinflammatory agents; asthma; carbonyl compound; chemical models; chemical synthesis; drug design /synthesis /production; furans; heterocyclic compounds; peptic ulcer; photochemistry; platelet activating factor; sesquiterpenes; shock; stereochemistry; stereoisomer

This grant application details our plans to utilize a chemical process based on the photocyloaddition of carbonyl containing compounds onto electron rich hetecrocycles such as furan. The reaction provides bicyclic photoadducts with excellent stereochemical control. These products can be converted to highly oxygenated target systems by subsequent functionalization procedures that have been developed during the current funding period. Our objectives for the research outlined in this proposal are: (1) to attempt new permutations of the reaction process that have been designed on the basis of a mechanistic hypothesis, (2) to apply the overall synthesis strategy to the preparation of several natural and unnatural products, the latter which (on the basis of a pharmacophore hypothesis) serve as potential drug candidates for treatment of arthritis, asthma, pepticulceration, and shock, and (3) to evaluate the predictive capabilities of these hypotheses by interpreting the results of mechanistic and synthetic studies and testing the biological properties of the drug candidates. On the basis of mechanistic considerations and preliminary findings the intramolecular photocycloaddition of 2-substituted furans is expected to result in an efficient route to highly unusual tricyclic ring systems. These materials will be converted to carbocycles with substitution patterns that are common in the natural products domain. Other specific aims include the identification of stereocontrol elements that will provide increased levels of chemo- and enantioselectivity in the photoaddition. Several applications of this strategy will be undertaken that are directed towards highly oxygenated members of the ginkgolide, alkaloid, germacranolide, and cembranolide classes. The structural homology of natural and unnatural platelet activating factor (paf) receptor antagonists is suggestive of a pharmacophore requirement for biological activity. Molecular modeling facilitates the design of new structures that may exhibit paf receptor antagonism. Such compounds are likely candidates for membership to the important class of nonsteroidal antiinflammatory agents. The furan-carbonyl photocyclo-addition reaction based strategy is central to our plans for the preparation of these new materials.

这份拨款申请详细说明了我们利用一种化学物质 基于含羰基化合物的光环加成的方法 化合物到富电子杂环如呋喃上。 的 反应提供了具有优异性能的双环光加合物， 立体化学控制。 这些产品可以转换为 通过随后官能化高度氧化的靶系统 在当前供资期间制定的程序 期 我们在本建议书中概述的研究目标 （1）尝试对反应过程进行新的排列， 已经被设计在一个机械假说的基础上，（2） 将整体合成策略应用于制备几种 天然和非天然产品，后者（基于 药效团假说）作为潜在的候选药物， 治疗关节炎、哮喘、消化不良和休克， (3)通过以下方式评估这些假设的预测能力 解释机械和合成研究的结果， 测试候选药物的生物学特性。 根据机械方面的考虑和初步结论， 发现2-取代的分子内光环加成 预计呋喃将导致一种高效的途径， 三环环系统。 这些材料将转化为 碳环的取代模式是常见的， 天然产物领域。 其他具体目标包括： 确定立体控制要素， 增加的化学和对映选择性水平， 光加成 这一战略的几个应用将是 针对高含氧成员开展的 银杏内酯、生物碱、吉马甘草酸和西布兰替 班 天然血小板与非天然血小板的结构同源性 活化因子（PAF）受体拮抗剂提示 生物活性的药效团要求。 分子 建模有助于新结构的设计， PAF受体拮抗作用 这些化合物很可能是 作为重要的非甾体类药物的成员， 间谍。 呋喃-羰基光环加成反应 基于反应的战略是我们准备计划的核心， 这些新材料。