Highly Efficient Electrocarboxylation Method to Synthesize Novel Acid Derivatives of 1,4-Dihydropyridines and to Study Their Antimicrobial Activity

1,4-Dihydropyridines (1,4-DHPs) hold a top-notch position in the pharmaceutical world due to a broader spectrum of applications, whereas the carboxylic moiety has been an integral part of the physiological world, effective food preservatives, and antimicrobial agents. Seeking the enormous potential and applications of these two classes, we worked to combine these to synthesize 2,2 '[3,5-bis(ethoxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]diacetic acid the novel dicarboxylic derivatives of 1,4-DHP (9a-k) achieved via the electrocarboxylation of tetrasubstituted-1,4-dihydropyridines (8a-k) derivatives using Mg-Pt electrodes in an undivided cell. The targeted compounds were established by 1H, 13C NMR, IR, and ESI-MS. Further, the synthesized compounds show excellent resistance against various microbes and the activity increased 2-3 folds after the introduction of acid groups. Compound 9b (against E. coli, S. aureus, B. subtilis, A. niger, and P. glabrum), 9d (against E. coli, K. pneumonia, S. aureus, A. janus, and F. oxysporum), 9f (against E. coli and P. fluorescens), and 9k (against F. oxysporum and P. glabrum) were found to be highly active at 4 mu g/mL with reference to standard amoxicillin and fluconazole. Further, the present synthetic protocol would open new gates for other researchers to develop new molecules by bioisosteres of these substrates.

Automated summary

In this study, a series of novel dicarboxylic derivatives of 1,4-dihydropyridines were synthesized using electrochemical methods. These compounds exhibited excellent antimicrobial activity against various microbes, and the introduction of acid groups significantly enhanced their activity.