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: 2392233
• 负责人: William H. Pearson
• 金额: $ 19.86万
• 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 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2392233
• 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、高效的合成方法 具有生物学意义的含有吡咯烷的分子。它是 注意到这类化合物将吡咯烷环结合到 这个结构有许多不同的形式。首席调查员 指示如果合成方法在访问 这一结构子功能，它可能有助于准备一个 目标分子种类繁多。拟议的研究是为了尝试 2-氮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点的横截面 分子。据称，其例子包括乙酰胆碱。 受体复合抑制剂(-)-吲哚利定209B、蚂蚁毒液和 新发现的抗癌药物--跟踪化合物(+)-单茂林 雷公藤生物碱抗疟、抗癌、抗菌作用 生物碱金雀花胺、抗癌化合物倍他西汀和 Pre criwell ine，一种中国民间药物的成分，用于治疗 风湿性心脏病的治疗 和惊厥的蒙丹宁型生物碱，令人兴奋的新止痛药 表巴替丁和具有药理活性的托烷生物碱(-)- 可卡因。还应该指出的是，已经被 目标是因为它们的结构新颖性或其未被探索的生物学 活性包括罗布麻素B、奥古斯丁、维他命、螺杆菌、 和红藻氨酸。 首席调查员表示，这些目标将允许 2-氮烯丙基阴离子环加成法适用范围的考察 有几种方法和注意到，例如，阴离子者的类型 所需的量在靶分子的范围内有很大的不同，从 从简单的烯烃到共轭的烯烃，如双烯和苯乙烯。他 报告说，所需的阴离子类型也是多种多样的。他建议 简单的脂肪族阴离子，杂取代阴离子，共轭 将需要阴离子和环状阴离子，每种阴离子都有其独特的 化学和制备方法。刻板印象控制的问题，两者 绝对和相对有待详细探讨。有关的资料 这些环加成反应的优选过渡态为 这些研究的结果。