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.

热引起的化学变化的知识是 对于任何化合物都具有根本意义。生物碱和 相关物质代表了一类重要的化合物，它们具有 对现代医学的发展发挥了重要作用。然而， 滥用该类别的某些成员（例如可卡因和海洛因） 造成严重的健康问题。由于各种原因，使用 的热量为 药物输送系统正变得越来越普遍（例如“裂纹 吸烟”）。为了全面评估相关的健康问题 对于滥用物质，重要的是要了解热量可能产生的作用 改变它们的化学成分。 我们解决这个问题的方法是研究热化学 气相生物碱。因为药物输送还涉及 气相，这些研究将深入了解气相的化学变化 这些药物可能在“快速吸烟”期间以及给予 深入了解可能发生的更复杂的化学过程 凝聚相。 我们对 (-)-可卡因的初步研究表明，它是热 在 550 摄氏度下不稳定，经历剧烈的结构转变 分成三种与可卡因无关的产品。这些初步研究是 非常令人鼓舞的表明生物碱的热反应不是 一个“极其复杂的问题”。我们计划研究可卡因的热分解 在不同的环境条件下，并将这些研究扩展到 与可卡因有关的其他生物碱。这些研究的结果 托烷生物碱将提供有关其热学的重要数据 反应和产物。这些知识连同生物学数据是 对于完全了解使用热量作为药物的影响至关重要 输送系统。 可卡因和相关生物碱的热化学完成后 我们将利用这些经验来扩大我们和相关生物碱的研究。 因为这个研究计划的目的是对 生物碱的热反应结果可能会影响 除与药物输送相关的问题外，与可卡因相关的问题。 特别是，我们相信我们的热研究结果表明 制备具有生物学意义的化合物的新方法。我们的 初步研究已经提出了一种制备方法 甲基芽康定的非共轭异构体，一种重要的生物碱 与从未被鉴定过的可卡因或其生物学特性有关 研究的属性。