Natural Product Inspired Diversity Oriented Synthesis of Tetrahydroquinoline Scaffolds as Antitubercular Agent

Abstract

An efficient natural product inspired diversity oriented syn thesis of tetrahydroquinoline analogues has been developed using the natural carbohydrate derived solid acid catalyst via multicomponent aza-Diels-Alder reaction of imine (generated in situ from aromatic amine and aldehyde) with dienophile in acetonitrile in a diastereoselective manner. The use of water as solvent reverses the diastereoselectivity toward the cis isomer. Interestingly, tricyclic pyrano/furano benzopyran with cis diastereoselectivity is obtained when salicylaldehyde is used as an alternative of aromatic aldehyde under the same condition. These synthesized quinolines and benzopyrans analogues have been evaluated for their Antitubercular activity against M. tuberculosis H₃₇Ra, and M. tuberculosis H₃₇Rv, and some of the analogues shows better activity profile than their natural product analogues. The protocol is not only mild, efficient, ecofriendly, but also involves reusable and biodegradable catalyst and provides route for both the diastereoisomer.

Bridged [2.2.1] bicyclic phosphine oxide facilitates catalytic γ-umpolung addition–Wittig olefination

“…The utility of this γ-umpolung/Wittig reaction was further explored in the synthesis of the furanoquinolines 13 , which have shown antitubercular activity ( Scheme 5 ). 23 For this synthesis, we reduced the ester 3a with lithium aluminum hydride (LAH), followed by iodoetherification with N -iodosuccinimide (NIS), to obtain the furan 9 in 82% yield over two steps. The core structure 10 was obtained after deiodination with RANEY® Ni.…”

Quinolines: Microwave-assisted synthesis and their antifungal, anticancer and radical scavenger properties

“…Then, the Povarov reaction, based on an inverse electron-demand aza-Diels-Alder reaction between an aniline, aldehyde and an electron-rich alkene to afford a tetrahydroquinoline, quinoline or julolidine, has long attracted the interest of synthetic chemists. This three-component reaction is reported to be catalyzed by BF 3 /Et 2 O, 14 lanthanide(III) triflates, 15 molecular iodine, 16 SnCl 2 , 17 TMSCl, 18 TEMPO salt (T + BF 4 À ), 19 acid 22 and triphenylmethylium cation. 23 Our group and others have used calix [n]arenes as organocatalysts in multicomponent reactions (MRCs), 24 including a Povarov reaction designed for the synthesis of julolidines.…”

Aluminum triflate catalyzed Povarov reaction for the synthesis of pyranotetrahydroquinolines

“…[1][2][3][4][5] Owing to their importance, a number of synthetic strategies have been developed for their synthesis. 1,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] The reaction of an aromatic imine (in a two component reaction) or aniline (in a three component reaction) with benzaldehyde and electron rich dihydropyran (DHP) in the presence of an acid catalyst/promotor, known as the Povarov reaction, 1,[19][20][21][22][23][24] has been the common and convenient synthetic protocol for the preparation of such important compounds. Several acid catalysts/promoters, which include the following, have been reported in the literature: InCl 3 , 9 Sc(OTf) 3 32 Tritylium Cation, 33 and phosphoric acid.…”