6533b7dcfe1ef96bd1272074
RESEARCH PRODUCT
Synthesis of C3/C1-Substituted Tetrahydroisoquinolines
Anna PipernoAngela ScalaFrancesco RisitanoGiovanni GrassiTanja SchirmeisterRaoudha Mezghani JarrayaMohamed MihoubiAmira BouazizNicola Micalesubject
Proteases<i>N</i>-methylisosalsolineStereochemistryPharmaceutical SciencenitroalkeneNitroalkene20s proteasomeArticleAnalytical Chemistrylcsh:QD241-441chemistry.chemical_compoundlcsh:Organic chemistryTetrahydroisoquinolinesN-methylisosalsolineDrug DiscoveryAnimalsHumansParasitesPhysical and Theoretical ChemistryBischler-Napieralski condensationCell ProliferationBischler-Napieralski condensation; N-methylisosalsoline; nitroalkene; proteasome; tetrahydroisoquinolineChemistryTetrahydroisoquinolineAlkaloidOrganic ChemistrySubstrate (chemistry)Hammada scopariaproteasomeChemistry (miscellaneous)Molecular MedicineCattleAmine gas treatingtetrahydroisoquinolinePeptide Hydrolasesdescription
A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline skeleton may be exploited as a template for the development of novel anticancer agents. In this article, we report the synthesis and chemical characterization of a new series of isosalsoline-type alkaloids (10-11) with variations at N2 and C3 positions with respect to the natural Compound 2, obtained by a synthetic strategy that involves the Bischler-Napieralski cyclization. The substrate for the condensation to the tetrahydroisoquinoline system, i.e., a functionalized β-arylethyl amine, was obtained through an original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-01 |