Synthesis of novel unsymmetrical coumarinyl-1,4-dihydropyridines

ABSTRACT

The novel unsymmetrical 3,5-dialkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines and 5-acetyl-3-alkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines (coumarinyl-1,4-dihydropyridines) have been synthesized by Knoevenagel condensation of 4-formyl-7,8-dimethoxycoumarin with alkyl acetoacetates in the presence of AlCl₃ followed by cyclization of the resulted Knoevenagel product with other alkyl acetoacetate or acetyl acetone and ammonium acetate. The structure of the intermediate Knoevenagel product and the cyclized unsymmetrical coumarinyl-1,4-dihydropyridines has been established on the basis of their spectral data analysis and single-crystal X-ray diffraction analysis. The observed conformation of the coumarinyl-1,4-dihydropyridines holds the key to promising calcium antagonistic activity of the synthesized coumarinyl-1,4-dihydropyridines.

GRAPHICAL ABSTRACT

KEYWORDS:

• 4-Formylcoumarin
• Lewis acid catalyst
• unsymmetrical courmarinyl-1,4-dihydropyridine

Acknowledgments

The authors thank CIF-USIC, University of Delhi for providing the NMR spectral and HRMS recording facility. V. K., P. R., and S. K. thank CSIR New Delhi for the award of Junior/Senior Research Fellowships. We are thankful to Sandeep Kumar, IISER Mohali for extending help in solving crystal data.

Additional information

Funding

The authors are grateful to the University of Delhi for providing financial support under DU-DST Purse grant to strengthen the research and development.