Synthesis of C3/C1-Substituted Tetrahydroisoquinolines

Abstract

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 OPEN ACCESSMolecules 2015, 20 14903 original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines.

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles

“…Isolated alkaloids from natural sources containing the tetrahydroisoquinoline moiety are broadly abundant in many biologically active compounds (Figure ). Higenamine 1 extracted from the leaves of Aristolochia brasiliensis has been recognized as an agonist for the β2-adrenergic receptor − and antimycobacterial and anti-inflammatory drugs. , The complex α-substituted tetrahydroisoquinoline, Noscapine 2 , revealed an antiproliferative activity against human prostate cancer cells. , Oleracin E 3 has been established as an antioxidant and antidepressant agent. , The catechol-derived tetrahydroisoquinoline alkaloid Salsolinol 4 plays an important role in pathogenic treatment associated with Parkinson’s diseases. − Despite thienoquinolines and thienoisoquinolines being poorly represented in nature, they are important compounds in medicinal chemistry. Related compounds exhibit antileukemic and antibacterial activities; also, they were proved as vasodilators …”

Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System

“…The IC 50 values were calculated with the program GraFit ® using the two-parameter equation. More detailed experimental protocols for the assays against each proteolytic activity of the 20S proteasome, as well as against bovine pancreatic α-chymotrypsin, are already reported elsewhere (see also Supplementary Materials ) [ 32 ]. Cat-B and Cat-L were purchased from Calbiochem, Darmstadt, Germany, and the related assays were performed as previously described [ 33 ].…”

Medicinal chemistry perspectives of 1,2,3,4-tetrahydroisoquinoline analogs – biological activities and SAR studies

“…Mihoubi and co-workers synthesized THIQ derivatives 56–57 via Bischler–Nepieralski cyclization ( Scheme 9 ). 17 Initially, compound 54 was obtained from vanillin 52 and nitropropane 53. The compound 54 was then subjected to Bischler–Nepieralski cyclization using POCl 3 to give the dihydroisoquinoline moiety 55 which was then reduced using NaBH 4 to give the titled compounds 56–57.…”