THERMAL REACTIONS OF (-)-COCAINE AND RELATED ALKALOIDS

(-)-可卡因和相关生物碱的热反应

• 批准号: 3212894
• 负责人: FRANK W FOWLER
• 金额: $ 6.06万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3212894
• 关键词: Diels Alder reaction; alkaloids; benzoates; chemical structure; chemical synthesis; cis trans isomerization; cocaine; codeine; drug abuse; drug delivery systems; gas chromatography; heat; heroin; isomer; isomorphous substitution; mass spectrometry; morphine; nuclear magnetic resonance spectroscopy; thermodynamics; thermostability; thin layer chromatography; tropanes

The knowledge of the chemical transformations induced by heat is of fundamental significance for any chemical compound. The alkaloids and related substances represent a important class of compounds that have played an important role in the development of modern medicine. However, the abuse of certain members of this class (eg. cocaine and heroin) is creating a substantial health problem. For a variety of reasons, the use of heat as a drug delivery system is becoming increasingly common (eg "crack smoking"). In order to completely evaluate the health problem associated with abused substances, it is important to understand the role heat may play in altering their chemical composition. Our approach to this problem will be to study the thermal chemistry of the alkaloids in the gas phase. Because the drug delivery also involves the gas phase, these studies will give insight into the chemical alteration of these drugs that may be occurring during "crack smoking" as well as giving insight into the more complex chemical processes that may be occurring in the condensed phase. Our preliminary studies on (-)-cocaine demonstrate that it is thermally labile at 550 degreesC undergoing a dramatic structural transformation into three products unrelated to cocaine. These preliminary studies are very encouraging indicating that the thermal reactions of alkaloids is not a "hopelessly complex problem." We plan study the thermolysis of cocaine under different environmental conditions and to extend these studies to other alkaloids associated with cocaine. The results of these studies on the tropane alkaloids will provide important data on their thermal reactions and products. This knowledge along with biological date is essential for a complete understanding the impact of using heat as a drug delivery system. Once the thermal chemistry of cocaine and related alkaloids is completed we will use the experience to expand our studies and related alkaloids. Because this research program is aimed at a basic understanding of the thermal reactions of the alkaloids the results may have an impact on problems related to cocaine other than those associated with drug delivery. In particular, we believe that the results of our thermal studies suggest new methods for the preparation of compounds of biological interest. Our preliminary studies have already sugggested a method for the preparation of the unconjugated isomer of methyl ecgonidine, an important alkaloid related to cocaine that has never been characterized or its biological properties studied.

热量引起的化学转化的知识是 任何化合物的基本意义。生物碱和 相关物质代表具有重要化合物的重要类 在现代医学的发展中发挥了重要作用。然而， 滥用该课程的某些成员（例如可卡因和海洛因）是 造成重大的健康问题。由于多种原因， 热量 药物输送系统变得越来越普遍（例如“裂纹） 吸烟”）。为了完全评估与健康问题有关 使用滥用物质，重要的是要了解热量可能 播放改变其化学成分。 我们解决这个问题的方法是研究 气相中的生物碱。因为药物输送也涉及 气相，这些研究将深入了解 这些在“裂缝吸烟”中可能发生的药物以及给予 深入了解可能发生的更复杂的化学过程 冷凝阶段。 我们对（ - ） - 可卡因的初步研究表明它是热的 在550 degreesc处不稳定，经历了巨大的结构转化 分成与可卡因无关的三种产品。这些初步研究是 非常令人鼓舞，表明生物碱的热反应不是 一个“绝望的复杂问题”。我们计划研究可卡因的热解 在不同的环境条件下，将这些研究扩展到 与可卡因相关的其他生物碱。这些研究的结果 Tropane生物碱将提供有关其热量的重要数据 反应和产品。这些知识以及生物约会是 完全了解使用热作为药物的影响至关重要 交付系统。 一旦可卡因和相关生物碱的热化学完成 我们将利用这一经验扩大我们的研究和相关的生物碱。 因为该研究计划旨在基本了解 生物碱的热反应结果可能会影响 与可卡因有关的问题除了与药物输送相关的问题。 特别是，我们认为我们的热研究结果表明 制备生物学兴趣化合物的新方法。我们的 初步研究已经提出了一种准备方法 未结合的异构体的甲基仿形的异构体，一种重要的生物碱 与从未有过特征或其生物学的可卡因有关 研究的属性。