Synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones, their in silico ADMET properties and in vitro antitumor activities

Abstract

We synthesized a series of dihydroisoindolo[2,1-a]quinolin-11-ones using the imino Diels–Alder reaction and evaluated their biological properties, finding a new hit in anticancer research.

Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones mediated by eutectic solvents

“…The easy isolation of the crude product, the recyclability and reusability of the DES together with the scalability of this methodology for the preparation of the target compound are key factors that highlight the benets of this synthetic procedure over other reported methodologies. [49][50][51][52][53]…”

“…To understand the different reactivity observed in the reactions performed with ortho -substituted anilines, and to get inside of the mechanistic pathway a set of experiments were performed (Scheme 3). It has been proposed that the reaction between anilines and 2-formylbenzoic acid in the Povarov reaction may led to the formation of an imine or and isoindolinone 52,53 which further undergo the cycloaddition step to assemble the isoindoloquinoline skeleton. In our hands, p -toluidine and 2-formylbenzoic acid did not react employing the DES at room temperature, however when the reaction was conducted under the optimal conditions the 3-hydroxy-isoindolinone 21 was isolated in 66% yield.…”

“…48 Finally, the synthesis of isoindolo[2,1- a ]quinolin-11-ones have been achieved by cyclization from N -aryl-3-hydroxyisoindolinones and N -vinyl lactams or aryl alkynes under BF 3 ·Et 2 O catalysed reaction, 49–51 and by the reaction between anilines, dienophiles and 2-formylbenzoic acid (Scheme 1). 52,53…”

“…48 Finally, the synthesis of isoindolo[2,1-a]quinolin-11-ones have been achieved by cyclization from N-aryl-3hydroxyisoindolinones and N-vinyl lactams or aryl alkynes under BF 3 $Et 2 O catalysed reaction, [49][50][51] and by the reaction between anilines, dienophiles and 2-formylbenzoic acid (Scheme 1). 52,53 All these synthetic efforts demonstrate the utility of the imino-Diels-Alder reaction in the obtention of ring-fused tetrahydroquinoline derivatives, however, environmental concerns regarding the impact of solvents and catalysts employed in this reaction demand the development of new methodologies. Motivated by this, herein we show our results directed to the obtention of dihydroisoindolo[2,1-a]quinolin-11(5H)-ones employing eutectic solvents as alternative and environmentally friendly reaction media (Scheme 1).…”

Rhodium-catalyzed aminoacylation of alkenes via carbonylative C–H activation toward poly(hetero)cyclic alkylarylketones

“…Poly(hetero)cyclic alkylarylketones and their derivatives (Scheme 1A, I–IV) serve as potent inhibitors of DNA gyrase and Topo II to elicit bioactivities in the treatment of bacterial infections and cancer. 5 Moreover, deoxygenated methylation derivatives of such ketones (Scheme 1A, V) can be employed for selective recognition of telomeric RNA G-quadruplexes, which could be used as targets for cancer treatment. 5 c ,6 Hence, exploring catalytic carbonylative approaches in a straightforward and precise manner to access such poly(hetero)cyclic alkylaryl-ketones is highly desirable and of great pharmacological/environmental value.…”