Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A
Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A
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DOI：
10.1021/np1007872
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发表时间：
2011-04-01
影响因子：
5.1
通讯作者：
Prisinzano, Thomas E.
中科院分区：
文献类型：
--
作者：
Lozama, Anthony;Cunningham, Christopher W.;Prisinzano, Thomas E.
As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerociane diterpene, salvinorin A, we report the synthesis and biological Characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted Methods Were: developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via; microwave assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization. Of the bent oxanorbornadiene system, possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analognes 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products:
