Domino Reactions of 1-Aroyl-3,4-dihydroisoquinolines with α,β-Unsaturated Aldehydes

Abstract

An efficient synthesis of pyrrolo[2,1-a]isoquinolines by a domino reaction from a variety of 3,4-dihydropyrrolo[2,1-a]isoquinolines and α,β-unsaturated aldehydes in the absence of catalyst in good yields under microwave irradiation, is reported.

Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer’s Disease Potential

“…Together with the cytotoxicity data of the new DHPPIQ Schiff bases ( 7–19 ), the IC 50 values of the previously synthesized parent aldehydes ( 3–6 ) are listed in Table 1 ; the cytotoxicity of 1 (R 1 = Et, R 2 = R 3 = OEt and R 4 = H) and 2 (R 1 = Et, R 2 = R 3 = OEt and R 4 = Ph), whose IC 50 values were comparable to those of the pairs 3 / 4 and 5 / 6 , were already reported [ 3 ].…”

“…According to an affordable and effective procedure previously reported by some of us [ 3 ], the synthesis of DHPPIQ 2-aldehydes 1–6 was accomplished through a domino reaction of 1-aroyl-3,4-dihydroisoquinolines with α,β-unsaturated aldehydes. The aldehyde derivatives 1–6 were condensed with 4-anisidine in anhydrous toluene to afford the aromatic Schiff bases 7–12 ( Scheme 1 ).…”

“…The ability of small organic molecules to evade or inhibit P-gp may favor their blood–brain barrier (BBB) crossing and distribution into the brain [ 9 ]. Taking this notion into account, the good P-gp inhibition capacity demonstrated for very similar DHPPIQ-containing derivatives [ 3 ], combined with the outputs of the MuSSeL web server, prompted us to experimentally investigate the interference of the newly synthesized DHPPIQ Schiff bases with three AD-related targets, namely ChE isoforms (AChE and BChE), a β-amyloid aggregation that is a hallmark of AD occurrence and MAO A and B.…”

“…DHPPIQ 2-carbaldehydes [ 3 ] and related carbonyl adducts [ 4 ] (structure I with major points of diversification in Figure 1 ), mostly Schiff bases, were recently synthesized by some of us and biologically evaluated. Several DHPPIQ derivatives showed high inhibitory potency toward P-gp, attaining sub-micromolar 50% inhibition of the cell population growth (IC 50 ) values, and the ability to reverse in vitro P-gp-mediated resistance in doxorubicin-resistant tumor cells [ 4 ].…”

Facile synthesis of pyrrolo[2,1-a]isoquinolines by domino reaction of 1-aroyl-3,4-dihydroisoquinolines with conjugated ketones, nitroalkenes and nitriles

“…Intramolecular reactions of 1-and 1,2-functionalized tetrahydro-, 1,2-and 3,4-dihydroisoquinolines are often used for annulation of the pyrrole core [31][32][33][34][35][36]. Recently, our group has demonstrated the preparation of functionally substituted on the pyrrole ring pyrrolo[2,1-a]isoquinolines based on domino reactions of 3,4-dihydro-1-aroylisoquinolines with electron-deficient alkynes, α,β-unsaturated aldehydes and cross-conjugated vinyl ethynyl ketones [37][38][39][40].…”