Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.
J Nat Prod
; 74(4): 718-26, 2011 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-21338114
ABSTRACT
As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane 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 analogues 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Opioides kappa
/
Diterpenos Clerodânicos
/
Alucinógenos
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos