FUNCTIONALIZED CANNABINOIDS

该研究的长期目标是开发高效的 C-11官能化δ-9 THC衍生物的不对称合成。 的 拟开发的综合方法将具有足够的通用性， 天然存在的大麻素，人类代谢产物家族， 类似物 到目前为止，还没有立体特异性方法用于有效的 δ-9系列的C-11官能化大麻素的合成。 的 拟议的研究将提供一个可靠的途径，这些化合物， 一种独特的环化反应的应用， 发现，并通过选择一个高度合适的萜烯片段联合收割机 橄榄酚衍生物 萜烯片段价格便宜，可在 高光学纯度（两种对映体实际上都是可用的）， 自身进行化学修饰。 大麻素发挥各种有用的 生理作用：镇痛，止吐，抗惊厥，治疗 青光眼等。 它们有可能用于治疗 鸦片戒断症状 目前有几种大麻素 临床使用的类似物。 因为最近的研究表明， 大麻素在受体水平发挥其生理作用， 重要的是开发适合于制备 放射性标记的化合物。 体内研究的工具选择 药物的药理学和代谢是PET和SPECT，因此 在最后阶段快速引入短寿命正电子发射体， 需要化学合成。 合成的发展， 适用于这种应用，对 有机化学家 建议的合成是理想的，这样的应用。 此外，这项研究将用于编写 大麻素的构象受限变体。 此类化合物 可以具有增强的活性或可以作为大麻素拮抗剂。

The long-term goals of the proposed research are to develop efficient asymmetric synthesis of C-11 functionalized delta-9 THC derivatives. The synthetic methodology to be developed will be general enough to be applied to naturally occuring cannabinoids, the family of human metabolites and analogs. To date there is no stereospecific method for the efficient synthesis of C-11 functionalized cannabinoids of the delta-9 series. The proposed research will provide a reliable route to these compounds through the application of a unique cyclization reaction which has been recently discovered, and by choosing a highly suitable terpene fragment to combine with an olivetol derivative. The terpene fragment is cheap, available in high optical purity (both enantiomers are in fact available), and it lends itself to chemical modification. Cannabinoids exert a variety of useful physiological effects: analgesic, antiemetic, anticonvulsant, treatment of glaucoma, and others. They have potential for use in the treatment of opiate withdrawal symptoms. There are currently several cannabinoid analogs in clinical use. Since it has recently been shown that cannabinoids exert their physiological effects at the receptor level, it is important to develop syntheses which are suitable for the preparation of radiolabelled compounds. The tools of choice for in vivo studies of the pharmacology and metabolism of drugs are PET and SPECT, therefore the rapid introduction of a short-lived positron emitter in the last stage of the chemical synthesis is required. The development of synthesis which are suitable for this application places the greatest demands on the organic chemist. The proposed syntheses are ideal for such applications. Furthermore, this research will be deployed for the preparation of conformationally restricted variants of the cannabinoids. Such compounds may have enhanced activity or may act as a cannabinoid antagonist.