用于麻醉受体介导现象的探针。38. 外消旋顺式-4a-乙基-2-甲基-1,2,3,4,4a,9a-六氢苯并呋喃并[2,3-c]吡啶-6-醇和外消旋顺式-2-甲基-4a-苯乙基-1,2,3,4,4a,9a-六氢苯并呋喃并[2,3-c]吡啶-6-醇的快速合成。
PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA. 38. AN EXPEDITIOUS SYNTHESIS OF RAC-CIS-4a-ETHYL-2-METHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO[2,3-c]PYRIDIN-6-OL AND RAC-CIS-2-METHYL-4a-PHENETHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO[2,3-c]PYRIDIN-6-OL.
作者信息
Iyer Malliga R, Deschamps Jeffrey R, Jacobson Arthur E, Rice Kenner C
机构信息
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Services, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415.
出版信息
Heterocycles. 2009 Jan 24;79(2009):1061. doi: 10.3987/COM-09-S(D)84.
Abstract
A high-yielding five-step synthesis of cis-benzofuropyridin-6-ols provided an improved route to compounds with low to subnanomolar affinity at opioid receptors and high antinociceptive potency. This synthesis provided the known rac-cis-4a-ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1a) in high yield, and the novel rac-cis-2-methyl-4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1b). It was achieved using NBS to prepare the key intermediate 7. Di-demethylation followed by subsequent displacement of the bromine by the phenolic ion in hot Et(3)N gave the desired 1a. The structure of 1a was confirmed by X-ray crystallography.
摘要
一种高产率的五步合成顺式苯并呋喃并吡啶 -6-醇的方法为合成对阿片受体具有低至亚纳摩尔亲和力且具有高抗伤害感受效力的化合物提供了一条改进路线。该合成方法以高产率得到了已知的外消旋 -顺式 -4a-乙基 -2-甲基 -1,2,3,4,4a,9a-六氢苯并呋喃并[2,3 -c]吡啶 -6-醇（1a）以及新型的外消旋 -顺式 -2-甲基 -4a-苯乙基 -1,2,3,4,4a,9a-六氢苯并呋喃并[2,3 -c]吡啶 -6-醇（1b）。它是通过使用NBS制备关键中间体7来实现的。脱二甲基化，然后在热的三乙胺中酚离子取代溴得到所需的1a。1a的结构通过X射线晶体学得到证实。
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