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Open AccessArticle

Synthesis of C3/C1-Substituted Tetrahydroisoquinolines

1
Laboratoire de Chimie des Substances Naturelles UR/11-ES-74, Faculté des Sciences de Sfax, Université de Sfax, Route de l’aeroport, BP 1171, 3000 Sfax, Tunisia
2
Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università degli Studi di Messina, Viale Annunziata, 98168 Messina, Italy
3
Dipartimento di Scienze Chimiche, Università di Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy
4
Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, D 55099 Mainz, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Derek J. McPhee
Molecules 2015, 20(8), 14902-14914; https://doi.org/10.3390/molecules200814902
Received: 22 July 2015 / Revised: 5 August 2015 / Accepted: 10 August 2015 / Published: 14 August 2015
(This article belongs to the Section Organic Chemistry)
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 (1011) 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. View Full-Text
Keywords: Bischler-Napieralski condensation; N-methylisosalsoline; nitroalkene; proteasome; tetrahydroisoquinoline Bischler-Napieralski condensation; N-methylisosalsoline; nitroalkene; proteasome; tetrahydroisoquinoline
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Mihoubi, M.; Micale, N.; Scala, A.; Jarraya, R.M.; Bouaziz, A.; Schirmeister, T.; Risitano, F.; Piperno, A.; Grassi, G. Synthesis of C3/C1-Substituted Tetrahydroisoquinolines. Molecules 2015, 20, 14902-14914.

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