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Updated: Apr 5, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis of C3/C1-Substituted Tetrahydroisoquinolines
Mohamed Mihoubi1, Nicola Micale2, Angela Scala3
1Laboratoire 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. mohamed.mihoubi@hotmail.fr.
Abstract:
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.
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