C1'-Azacycloalkyl Hexahydrocannabinols
C1'-Azacycloalkyl Hexahydrocannabinols
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C1-氮杂环烷基六氢大麻酚
DOI：
10.1021/acs.joc.7b00988
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发表时间：
2017
影响因子：
3.6
通讯作者：
Alexandros Makriyannis
中科院分区：
文献类型：
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作者：
Thanh C. Ho;Naoyuki Shimada;Marcus A. Tius;Spyros P. Nikas;Wen Zhang;Alexandros Makriyannis
我们报道了一类新的大麻能配体C1 ′-氮杂环烷基六氢大麻酚的设计、合成和生物活性评价。我们的合成方法利用先进的常见手性中间体三氟甲磺酸酯，所有类似物都可以衍生。关键的合成步骤包括微波辅助Liebeskind-Srogl C-C交叉偶联和钯催化脱羧偶联反应。C1 ′-N-甲基氮杂环丁烷和C1 ′-N-甲基吡咯烷类似物是CB 1和CB 2大麻素受体的高亲和力配体。
We report the design, synthesis, and biological evaluation of a novel class of cannabinergic ligands, namelyC1′-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. TheC1′-N-methylazetidinyl andC1′-N-methylpyrrolidinyl analogues were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors.