Abstract
•Highly inexpensive chiral resolution of eight enantiomers of antibacterial agents.•Simulation studies of chiral resolution of eight enantiomers of antibacterial agents.•Mechanism of the chiral resolution of eight enantiomers of antibacterial agents.•Highly effective method for developing more effective antibacterial medication.
Some bacteria are resistant to the few antibiotics, which are being used to treat bacterial diseases. Therefore, there is a great need of new antibacterial compounds. Two antibacterial compounds were synthesized with two chiral centres in each molecule. The stereomers have different pharmacutical activities and, therefore, the efforts were made to resolve four stereomers on Chiral (+)-Crownpack column (250 mm × 4.6 mm, 5 µm) using 50 mM H2SO4 as mobile phase. The values of the retention, separation and resolution factors of four resolved stereomers of 13-methyl-11-phenyl-12-oxa-2,15-diazatetracyclo[8.6.0.03,8.011,15]hexadeca-1(10),3(8),4,6-tetraene-9,16-dione (I) were 0.36, 1.26, 2.15 & 3.42; 3.50, 1.70, & 1.59 and 3.54, 3.55 & 3.80 while these values for 6,13‐dimethyl‐11‐phenyl‐12‐oxa‐2,15-diazatetracyclo[8.6.0.03,8.011,15] hexadeca‐1(10),3(8),4,6‐tetraene‐9,16‐dione (II) were 0.44, 1.38, 2.50 and 6.66; 3.13, 1.81 and 2.66 and 4.72, 6.06 and 1.53, respectively. The values of the detection limits of four stereomers of I and II were 5.8, 2.5, 2.1 & 8.0 and 3.6, 2.0, 5.4 & 7.8 ng. The mechanism of the chiral separation of four stereomers was developed using modeling studies. The hydrogen bondings were responsible for the chiral resolution. The binding energies of the stereomers; with the chiral column; were in the range of −3.0 to −3.5 Kcal/mol. The developed method may be used to separate four stereomers of these two compounds to get optically active drugs.