Synthesis of new aminoglycerol derivatives as potential antibacterial agents

Based on our previous work in the synthesis of new small libraries of compounds with potential antimicrobial activity [1,2] the major aim of this report is to present the design and synthesis of three collections of urea derivatives from aminoglyceroles as new potential antibacterial agents. The prototype was 1-(4-Chlorophenyl)-3-[2,3-bis-(2-methyilbenzoyloxy)propyl]urea, that has shown antibacterial activity against colistin-resistant clinical strains of Acinetobacter baumannii. A central core was an aminoglycerol, that was functionalized with a urea group on the nitrogen atom, because it could be important for biological activity [1], and alcoholic functions were both functionalized with acyl groups. According to these result three new collections of prototype analogues were synthesized by a short and high yielded methodology. The 3-amino1,2-propanediol, commercially available, was employed as precursor of new compounds. In the first route, the urea group was introduced through reaction with different substituted phenylisocyanates. In the second route, sulfonic ester group or acyl functions with electron withdrawing or electron donating groups were introduced, to obtain the final molecules. The antibacterial activity of synthesized compounds was evaluated against seven strains representing different types of gram-positive and gram-negative bacteria: Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumonia, Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica, Serratia mercescens. Antifungal activity is also evaluated against Candida albicans.