NEW SYNTHETIC APPLICATION OF BENZENE PHOTOCHEMISTRY

苯光化学合成新应用

• 批准号: 3438887
• 负责人: RICHARD P JOHNSON
• 金额: $ 11.5万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438887
• 关键词: antineoplastics; benzene; carbopolycyclic compound; drug design /synthesis /production; molecular asymmetry; photochemistry

The proposed research will explore the limitations and synthetic potential of several photochemical reactions of benzene derivatives, with the goal of providing new or improved approaches to polycyclic molecules such as natural products, anti-tumor agents, and pharmaceuticals. One major objective is to improve the efficiency of the benzene meta cycloaddition so that higher yields may be obtained and more complex synthons might be employed. A second broad objective is asymmetric organic photochemistry. Asymmetric induction in meta cycloadditions to benzene will be studied, with specific application to known precursors to modhephene and isoiridomyrmecin. Another goal is efficient trapping of photogenerated benzvalene intermediates either by acid catalyzed nucleophilic addition or metal catalyzed rearrangements. The generality and regiochemistry of these reactions will be explored as a basis for further studies and more specific applications in synthesis. Although bacterial pneumonia is one of the leading causes of death amongst alcoholics, little knowledge exists concerning alcohol-related changes in pulmonary defense mechanisms against inhaled pathogens. The overall goal of this proposed research is to evaluate pulmonary defense mechanisms in animals who have ingested alcohol. Mice will be administered alcohol either acutely, via intragastric gavage, or chronically, by placing the alcohol in the diet. Following ingestion, alteration in pulmonary defenses will be analyzed on cellular and tissue levels in the presence or absence of bacterial endotoxin. Special emphasis will be placed on alterations in alveolar macrophage function. Because of their strategic location in the lung, pulmonary alveolar macrophages play a central role in the response of the lung to inhaled pathogens. Following alcohol ingestion and/or pulmonary endotoxin exposure, macrophage function will be evaluated, in vitro, by measuring alterations a) in plasma membrane integrity, b) in phagocytosis, C) in superoxide production and d) in the ability of the macrophages to secrete mediators (cytokines and products of arachidonic acid metabolism) of inflammation. Whole lung response will be evaluated by a) examining bronchoalveolar lavages for the presence of inflammatory cells and mediators, b) morphometrically evaluating the site and extent of lung injury following exposure and c) in vivo microscopic evaluation of inflammatory processes occurring in the pulmonary microvasculature. Data obtained from these ,experiments should aid in determining the site(s) of alcohol induced dysfunction in pulmonary defense mechanisms.

拟议的研究将探讨限制和合成潜力 苯衍生物的几种光化学反应，目标是 为多环分子提供新的或改进的方法， 天然产物、抗肿瘤剂和药物。一个主要 目的是提高苯Meta环加成反应的效率 从而可以获得更高的产率， 就业。第二个广泛的目标是不对称有机光化学。 将研究苯的Meta环加成反应中的不对称诱导， 具体应用于已知的莫达非的前体， 异鸢尾霉素另一个目标是有效地捕获光生的 通过酸催化的亲核加成或 金属催化重排这些的一般性和区域化学 反应将作为进一步研究的基础进行探讨， 在合成中的具体应用。 虽然细菌性肺炎是导致死亡的主要原因之一， 酗酒者，关于酒精相关的变化知之甚少， 肺防御机制对吸入的病原体。总目标 这项研究的目的是评估肺防御机制， 摄入酒精的动物。小鼠将被给予酒精 无论是急性，通过胃内灌胃，或慢性，通过放置 饮食中的酒精摄入后，肺部防御功能的改变 将在细胞和组织水平上进行分析， 细菌内毒素将特别强调以下方面的改动： 肺泡巨噬细胞功能由于其战略位置， 肺，肺泡巨噬细胞在反应中起中心作用 吸入的病原体。酒精摄入后和/或 肺内毒素暴露，将评价巨噬细胞功能， 体外，通过测量a）质膜完整性，B） 吞噬作用，C）超氧化物的产生和d）超氧化物的能力。 巨噬细胞分泌介质（细胞因子和花生四烯酸的产物） 酸代谢）的炎症。将通过以下方式评价全肺缓解： a）检查支气管肺泡灌洗液中炎性细胞的存在， 细胞和介质，B）形态计量学评估 暴露后的肺损伤和c）体内显微镜评价 在肺微血管中发生的炎症过程。数据 从这些获得，实验应有助于确定网站（S） 酒精诱导的肺防御机制功能障碍。