Synthesis and antitubercular evaluation of novel dibenzo[b,d]furan and 9-methyl-9H-carbazole derived hexahydro-2H-pyrano[3,2-c]quinolines via Povarov reaction

A series of novel hexahydro-2H-pyrano[3,2-c]quinoline analogues derived from dibenzo[b,d]furan and 9-methyl-9H-carbazole has been synthesized in very good yields through SnCl2·2H2O catalyzed one-pot Povarov reaction (imino-Diels–Alder reaction). The imines generated in situ from dibenzo[b,d]furan-2-carbaldehyde or 9-methyl-9H-carbazole-3-carbaldehyde and aromatic amines, were reacted with 3,4-dihydro-2H-pyran in a diasteroselective manner in acetonitrile at RT. These synthesized isomeric pyranoquinoline analogues have been evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) by agar dilution method. Among the 23 compounds screened, 5-(dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline 4f, 5-(dibenzo[b,d]furan-2-yl)-9-fluoro-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline 5f and 9-fluoro-5-(9-methyl-9H-carbazol-3-yl)-3,4,4a,5,6,10b-hexa hydro-2H-pyrano[3,2-c]quinoline 7f (MIC 3.13 μg/mL) were resulted as most active antitubercular agents.

A series of novel hexahydro-2H-pyrano[3,2-c]quinoline analogues synthesized via SnCl2·2H2O catalyzed one-pot Povarov reaction, resulted three compounds (MIC 3.13 μg/mL) as most potent molecules against in vitro Mycobacterium tuberculosis H37Rv (MTB).Figure optionsDownload as PowerPoint slideHighlights
► Described the concept of integrating two bioactive units in one molecular frame to achieve newer MTB actives.
► Synthesis of dibenzofuran and carbazole derived hexahydropyranoquinolines is achieved via Povarov reaction.
► Three new analogues were resulted as active antitubercular agents against M. tuberculosis H37Rv.