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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.

DOI:10.3987/COM-09-S(D)84
PMID:20101277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2714916/
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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/30e0019ef80c/nihms97784f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/84859f8c40bf/nihms97784f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/384c25fc96a6/nihms97784f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/2025d149fa7c/nihms97784f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/a57eb921b354/nihms97784f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/30e0019ef80c/nihms97784f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/84859f8c40bf/nihms97784f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/384c25fc96a6/nihms97784f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/2025d149fa7c/nihms97784f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/a57eb921b354/nihms97784f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90b/2714916/30e0019ef80c/nihms97784f5.jpg

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1
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J Med Chem. 2008 Dec 25;51(24):7866-81. doi: 10.1021/jm800913d.
2
Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans.邻位和对位电子和呋喃氧化物桥连苯基吗啡烷的N-苯乙基类似物对映体的合成及药理作用
Org Biomol Chem. 2008 Aug 21;6(16):2868-83. doi: 10.1039/b803433h. Epub 2008 Jun 13.
3
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J Med Chem. 2007 Aug 9;50(16):3765-76. doi: 10.1021/jm061325e. Epub 2007 Jul 11.
4
Probes for narcotic receptor-mediated phenomena. 33. Construction of a strained trans-5,6-ring system by displacement of a nitro-activated aromatic fluorine. synthesis of the penultimate oxide-bridged phenylmorphans.用于麻醉受体介导现象的探针。33. 通过硝基活化的芳族氟的取代构建张力反式5,6-环系统。倒数第二个氧化桥连苯基吗啉的合成。
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5
Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.人类因哌替啶类似物合成产物导致的慢性帕金森症。
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6
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7
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NIDA Res Monogr. 1984 Mar;49:109-13.
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