Synthesis of C3/C1-Substituted Tetrahydroisoquinolines

Molecules

Mohamed Mihoubi³  Nicola Micale¹  Angela Scala²  Raoudha Mezghani Jarraya³  Amira Bouaziz³  Tanja Schirmeister⁴  Francesco Risitano²  Anna Piperno²  Giovanni Grassi² 

[1] Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università degli Studi di Messina, Viale Annunziata, 98168 Messina, Italy; E-Mail:;Dipartimento di Scienze Chimiche, Università di Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, Italy; E-Mails:;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; E-Mails:;Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, D 55099 Mainz, Germany; E-Mail:

关键词: Bischler-Napieralski condensation;    N-methylisosalsoline;    nitroalkene;    proteasome;    tetrahydroisoquinoline;   

DOI  :  10.3390/molecules200814902

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.