Green one-pot synthesis and in vitro antibacterial screening of pyrano[2,3-c]pyrazoles, 4H-chromenes and pyrazolo[1,5-a]pyrimidines using biocatalyzed pepsin

Abstract

In recent years, there has been a lot of interest in the modern organic synthesis using enzymes as biocatalysts. A multicomponent reaction of 4-formylphenyl benzoates, malononitrile, and pyrazolones utilizing pepsin as a biocatalyst was investigated in different reaction conditions. The best yields of pyrano[2,3-c]pyrazoles were obtained by grinding the respective reactants in a mortar in the presence of pepsin for 1.5–2 h at room temperature. Instead of pyrazolones, 1,3-cyclic diketones and 4-arylazo-5-aminopyrazoles were used to prepare new series of 4H-chromenes, and pyrazolo[1,5-a]pyrimidines in good to excellent yields after grinding the respective reactants for 0.5–3 h. The new target molecules showed a wide range of antibacterial activity against four different ATCC bacterial strains. The pyrazolo[1,5-a]pyrimidines 14a and 14f displayed moderate antibacterial activity against the K. pneumoniae and S. aureus strains with inhabitation zones of 29.6–30.3 mm and MIC values of 125–250 μg/mL.

Graphical Abstract

Keywords:

• Biocatalyzed reactions
• cycloaddition
• green chemistry
• MCR
• pepsin