1,5-Benzoxazepines vs 1,5-benzodiazepines. one-pot microwave-assisted synthesis and evaluation for antioxidant activity and lipid peroxidation inhibition.
Amino-1,5-benzoxazepines 2 and 5 and hydroxyl-1,5-benzodiazepines 3 and 6 have been synthesized in one-pot solvent-free conditions from 2,3-diaminophenol and ketones through microwave assisted acid catalysis, the benzoxazepine/benzodiazepine ratio depending on the R(1) and R(3) aryl substituents. The otherwise inaccessible and unknown 2,2-dimethyl-4-aryl-1,5-benzodiazepines 8 were also prepared in an analogous manner. The reaction mechanism was investigated by means of DFT calculations. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved on the basis of the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS, and elemental analysis data, whereas the presence of an amino group in 5 and of a hydroxyl in 6 was confirmed by derivatization. Compounds 2, 3, 5f, 6a, 6c, 6d, 6f, 6h, 8c, and 12 were evaluated as antioxidants and lipid peroxidation inhibitors in vitro. Compound 6f was also evaluated as anti-inflammatory agent in vivo. Compounds 2 and 6f were found to be the most potent as inhibitors of lipoxygenase and of lipid peroxidation, respectively.
Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece.
Constantinos G
CG
Neochoritis
Constantinos A
CA
Tsoleridis
Julia
J
Stephanidou-Stephanatou
Christos A
CA
Kontogiorgis
Dimitra J
DJ
Hadjipavlou-Litina
D000975:Antioxidants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008872:Microwaves; D010077:Oxazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D000975:Antioxidants; D010077:Oxazepines; D001569:Benzodiazepines