ALKALOID SYNTHESIS VIA 2-AZAALLYL ANION CYCLOADDITIONS

通过 2-氮杂烯丙基阴离子环加成合成生物碱

• 批准号: 6033464
• 负责人: William H. Pearson
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6033464
• 关键词: alkaloids; alkenes; chemical addition; chemical synthesis; pyrrolidines

DESCRIPTION: The principal objective of the proposed research is to develop a new, general, and efficient method for the synthesis of pyrrolidine-containing molecules of biological significance. It is noted that such compounds have the pyrrolidine ring incorporated into the structure in many different fashions. The principal investigator indicates that if a synthetic method were general enough in accessing this structural subfeature, it may be useful for the preparation of a wide variety of target molecules. The proposed research is to attempt to use the anionic (3+2) cycloaddition of 2-azaallyl anions with alkenes for the construction of a cross-section of biologically relevant target molecules. It is stated that examples include the acetyl choline receptor complex inhibitor (-)-indolizidine 209B, the ant venom and trail-following compound (+)-monomorine, the newly discovered anticancer alkaloid lapidaformine, the antimalarial, anticancer and antibacterial alkaloid crinamine, the anticancer compounds pretazettine and precriwelline, a component of a Chinese folk medicine used for the treatment of rheumatic heart disease known as scandine, the hypotensive and convulsive montanine-type alkaloids, the exciting new analgesic epibatidine, and the pharmacologically active tropane alkaloid (-)- cocaine. It is further noted that other compounds which have been targeted due to their structural novelty or their unexplored biological activity include lapidilectine B, augustamine, vittatine, aspidospermine, and homoerythratine. The principal investigator indicates that these targets will allow examination of the scope of the 2-azallyl anion cycloaddition method in several ways and notes that for example, the type of anionophile required varies considerably across the range of target molecules, from simple alkenes to conjugated alkenes such as dienes and styrenes. He reports that the types of anions required are also diverse. He suggests that simple aliphatic anions, heterosubstituted anions, conjugated anions, and cyclic anions will be required, each with their unique chemistry and method of preparation. The issue of stereocontrol, both absolute and relative is to be explored in detail. Information on the preferred transition state for these cycloadditions is to obtained as a result of these studies.

描述：拟议研究的主要目标是 开发一种新的，通用的，有效的合成方法， 具有生物学意义的含吡咯烷的分子。 是 注意到这样的化合物具有结合到 以各种不同的方式构建。 主要研究者 表明，如果一个合成方法足够普遍， 这一结构子特征，它可能是有用的， 各种各样的目标分子。 这项研究旨在尝试 利用2-氮杂烯丙基阴离子与烯烃的阴离子（3+2）环加成反应 用于构建生物相关靶的横截面 分子。 据称，实例包括乙酰胆碱 受体复合物抑制剂（-）-indolizidine 209 B，蚂蚁毒液和 新发现的抗癌化合物（+）-monomorine 抗疟疾、抗癌和抗菌的生物碱拉皮达福明 生物碱crinamine，抗癌化合物pretazettine和 前克里维林，一种中国民间药物的成分，用于 风湿性心脏病的治疗称为scandine， 以及令人兴奋的新型止痛药- epibatidine，和活性托烷生物碱（-）- 可卡因 还应注意的是，已经被制备的其他化合物也可以用于制备。 由于其结构新奇或其未经探索的生物学特性而成为目标 活性包括拉匹地勒汀B、Augustamine、vittatine、aspidospermine 和高赤藓氨酸。 首席研究员表示，这些目标将允许 2-氮杂烯丙基阴离子环加成方法的范围的检查 几种方法，并注意到，例如，亲阴离子的类型 所需的靶分子范围有很大的不同，从 简单烯烃转化为共轭烯烃如二烯和苯乙烯。 他 报告称，所需的阴离子类型也多种多样。 他建议 简单的脂肪族阴离子，杂取代的阴离子，共轭的 阴离子和环状阴离子将需要，每一个都有其独特的 化学和制备方法。 立体控制的问题， 绝对和相对的，都要详细研究。 信息 这些环加成反应的优选过渡态是作为 这些研究的结果。