C1'-氮杂环烷六氢大麻酚类化合物。

C1'-Azacycloalkyl Hexahydrocannabinols.

机构信息

Department of Chemistry, University of Hawaii at Manoa , 2545 The Mall, Honolulu, Hawaii 96822, United States.

Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University , 360 Huntington Avenue, 116 Mugar Hall, Boston, Massachusetts 02115, United States.

出版信息

J Org Chem. 2017 Aug 4;82(15):7839-7849. doi: 10.1021/acs.joc.7b00988. Epub 2017 Jul 17.

DOI:10.1021/acs.joc.7b00988

PMID:28677397

Abstract

We report the design, synthesis, and biological evaluation of a novel class of cannabinergic ligands, namely C1'-azacycloalkyl hexahydrocannabinols. Our synthetic approaches utilize an advanced common chiral intermediate triflate from which all analogues could be derived. Key synthetic steps involve microwave-assisted Liebeskind-Srogl C-C cross-coupling and palladium-catalyzed decarboxylative coupling reactions. The C1'-N-methylazetidinyl and C1'-N-methylpyrrolidinyl analogues were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors.

摘要

我们报告了一类新型大麻素配体的设计、合成和生物学评价，即 C1'-氮杂环烷基六氢大麻醇。我们的合成方法利用了一种先进的共同手性中间体三氟甲磺酸酯，所有类似物都可以从该中间体衍生而来。关键的合成步骤包括微波辅助的 Liebeskind-Srogl C-C 交叉偶联和钯催化的脱羧偶联反应。C1'-N-甲基氮杂环丁烷基和 C1'-N-甲基吡咯烷基类似物被发现是 CB1 和 CB2 大麻素受体的高亲和力配体。