Indium(III) Chloride Catalyzed Convergent, Regioselective Synthesis of Annulated Quinoline and Pyridine Derivatives

Abstract

A direct convergent two-component regioselective synthesis of annulated pyridine motif from 1-aminopenta-1,4-diene fragment and aromatic aldehyde by indium(III) chloride catalyzed reaction has been developed through a concerted pathway. A series of potentially bioactive pyranoquinoline, phenanthroline, and pyridopyrimidine derivatives has been synthesized in high yields by this protocol.The pyridine and quinoline derivatives play a central role as versatile building blocks of many natural products. 1 Many methods are available for the synthesis of quinoline and pyridine scaffolds containing derivatives due to their broad spectrum of biological activities with antiasthmatic, antibacterial, antimicrobial, anti-inflammatory, antipyretic, antidiabetic, cytotoxic, and also having tyrosine kinase inhibition properties. 2 Recently, it has been found that substituted pyridines efficiently inhibit HMG-CoA reductase and cholesterol transport proteins. 3 It was also shown that quinoline derivatives can be used as a functional material for the preparation of nano and meso structures with enhanced photonic and electronic properties. 4 On the other hand natural products possessing coumarin, quinolone, and uracil subunits show a wide range of bioactivity. 5 Among them pyranoquinoline and phenanthroline are main scaffolds of many bioactive alkaloids 6 viz. amphimedine, dutadrupin, helietidine, and geibalansine. 7 Again pyranoquinoline derivatives are used as potential pharmaceuticals for their psychotropic, antiallergic, and estrogenic activity. 8 Recently, the pyridopyrimidine derivatives has gained enhanced importance because of their biological and medicinal applications such as antibacterial, 9 antiallergic, 10 and CNS stimulants, 11 and inhibitors of enzyme adenosine kinase (AK) 12 or dihydrofolatereductase (DHFR). 13 Moreover, due to bioactivities these low-molecular-weight heterocycles have received considerable attention in pharmaceutical and agrochemical sectors. 14 These biodynamic properties associated with pyridopyrimidine, pyranoquinoline, and phenanthroline derivatives have made the synthesis of these molecules more demanding.As a part of our program aiming at developing selective and environmentally friendly methods for the synthesis of biodynamic heterocycles 15 we explored novel synthetic strategies for the synthesis of annulated pyridine and quinoline, that is, pyridopyrimidine, pyranoquinoline, and phenanthroline derivatives. Besides traditional approaches, 16 the last two decades have seen the development of a number of useful methods for the synthesis of quinoline and pyridine derivatives, which include metal-catalyzed reaction, radical-mediated cyclization, iodine-mediated reaction, or Lewis acid catalyzed reaction. 17 These are certainly improvements over traditional approaches, but also have some limitations. Some are time consuming, not environmentally benign, required harsh reaction conditions or multistep reaction. In recent years, enormous progress has been made in expanding the scope of the direct ad...

An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest

“…In 2012, Majumdar et al, reported the synthesis of pyrido [3,2- f ]coumarins 168a – f by the Indium (III) chloride-catalyzed reaction of 5-allyl-6-aminocoumarin ( 167 ) with benzaldehydes 51 [ 123 ]. In the proposed mechanism, the imine A formed from 167 and 51a in the presence of InCl 3 at first, followed by an 1,5-H shift to the intermediate B .…”