Synthesis and Antibacterial Activity of Novel Cyclic α-Aminophsophonates

Synthesis of novel I±-aminophsophonates 4 and 7 was accomplished at room temperature with good yields by three one-pot reaction of glutaraldehyde...


Bacterial Strains
The antibacterial activity of different chemical compounds

Compounds Preparation for Antimicrobial Activity
Compounds were dissolved in Dimethyl sulfoxide (DMSO), and then a final concentration of 100mg/ml was prepared using sterile distilled water. Control DMSO was used to check the effect of solvent on the growth of microorganisms.

Agar Well Diffusion Method
A volume of 100μl bacterial suspension (10 6 CFU/ml) was spread on Müller-Hinton agar (Oxoid, UK). Wells were made on agar plates using sterile cork borer, and then 100 μl of each prepared compound was introduced into appropriately marked wells, then plates were incubated for 24 h at 37°C. DMSO was taken as a negative control. Antibacterial activity was evaluated by measuring the diameter of the inhibition zone in millimeters for each tested organism compared with the negative control [15].

Result and Discussion
Chemistry A newly synthesized compounds of cyclic α-aminophsophonates were performed by three one pot reaction of glutaraldehyde 1 (0.24 mL, 2 mmol), with various diamines 2 (2 mmol) and triphenyl phosphite 3 (0.39 mL, 2 mmol) in presence of (LiClO 4 ) in acetonitrile with equal molar ratio (1:1:1) to afford 5 in good yields as shown in scheme 1. In structure characterization of 5, the IR spectra showed the absorption bands of (NH 2 ) ranging from 3432 to 3291cm -1 and (P=O) from 1367 to 1226 cm -1 . The 1 H-NMR spectra showed the chemical shift of (CH-P) as singlet peak ranging from δ: 6.00 to 6.08 ppm which affirmed the formation of α -aminophosphonate. It is noticeable that the absence of the aldehydic group (CHO) in 1 H-NMR confirmed the formation of cyclic α-aminophosphonates through intra molecular cyclization followed by water elimination [17,18].
The EI mass spectra confirmed the formation of 5 throughout the coincidence of the molecular ion peak with expected mass.

Scheme 1: Synthesis of α-aminophosphonate.
The recommended mechanism for preparation of cyclic α-aminophosphonates using LiClO 4 as a catalyst illustrated in

Biological Evaluation
In vitro, two groups of synthetic chemical compounds, cyclic α-amino phosphonate using tri phenylphosphiteand cyclic α-amino phosphonate bearing quinolone moiety, were tested against MDR strains of E.coli and K. pneumonia that already resistant to ciprofloxacin [17], Staphylococcus aureus ATCC25923, MRSA S. aureus, and finally clinical Candida albicans using well diffusion method and the data analyzed as recommended by CLSI [18].

Conclusion
The formation of novel cyclic α-aminophsophonate was installed by three one pot reaction of glutaraldehyde, various diamine derivatives and di or triphenylphsopite in presence of LiClO 4 as a catalyst. It was reported that these newly synthesized compounds have potent activity against Klebsiella pneumonia and E. coli bacteria.