TiCl4/nano-sawdust as an Efficient Biocatalyst for the Synthesis of Highly Substituted Dihydro- 2-oxopyrroles as Antimicrobial Agents

Aim: Sawdust nano particles was prepared from the pine wood and applied for the synthesis of TiCl4/nano-sawdust as a readily available, inexpensive, biodegradable and environmentally benign heterogeneous solid acid biocatalyst. The catalyst was used for the one pot cascade synthesis of highly functionalized dihydro-2-oxypyrroles (S1-S18). On the other hands, fungal and bacterial infections are always regarded as a dangerous pathogen. Because of increased resistance to microbial strains need to discover new antimicrobial drugs. Here we evaluated the antimicrobial activities of these compounds against different species of micro organisms including gram-positive and gram-negative bacteria as well as fungi.

Methods: Four-component reactions (4CRs) of the dialkyl acetylenedicarboxylates, amines and aldehydes were used for the synthesis of highly functionalized dihydro-2-oxypyrroles under thermal conditions. A micro-dilution susceptibility test and disk diffusion methods were used to study the antimicrobial activity of the new compounds against different species of gram-positive and gram-negative bacteria and also Candida albicans microorganisms.

Results: The results showed that catalytic activity of TiCl4/nano-sawdust for the synthesis of dihydro-2-oxopyrroles via 4CRs of the dialkyl acetylenedicarboxylates, amines and aldehydes. Also, dihydro-2-oxopyrrole derivatives had moderate antimicrobial activity against pathogenic bacteria and fungi. The most of compounds are nearly antifungal active in comparison to the control drugs. Also, MIC values of the synthetic compounds showed ethyl 1-(4-ethylphenyl)-4-((4-ethylphenyl)amino)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate (S6), ethyl 5-oxo-1-(p-tolyl)-4-(p-tolylamino)-2,5-dihydro-1H-pyrrole-3-carboxylate (S7) and ethyl 1-(4-methoxyphenyl)-4-((4-methoxyphenyl)amino)-5-oxo-2,5-dihydro-1H-pyrrole-3- carboxylate (S8) exhibited strong inhibitory activities against gram positive bacteria.

Conclusion: In summary, TiCl4/nano-sawdust as a green, cheap, natural, biodegradable and readily available biopolymer solid acid catalyst introduced for synthesis of dihydro-2-oxopyrrole derivatives. Comparing the structure and activity of these compounds showed that adding ethyl residue in the 4-position of phenyl ring of dihydro-2-oxopyrroles increased their antibacterial activities.