Synthesis, spectral characterization, and pro- and antioxidant activity of phosphorylated derivatives of cis-tramadol
A series of new N-phosphorylated derivatives of cis-tramadol were synthesized in a two-step process with good yields to evaluate the pro- and antioxidant activities (LPO, NO2−, total SOD, and CAT). In the first step, cis-tramadol (1) was treated with 4-nitro/2-chlorophenyl phosphorodichloridate (2/3) in the presence of triethylamine (TEA) to yield the intermediates (4/5). Further these were subsequently treated with various primary and secondary amines in the presence of TEA to afford (1R)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexyl substituted phosphonates/phosphoramidates (6a-f/7a-f). Their structures were established by IR, NMR (1H, 13C, 31P), mass spectra, and C, H, N analysis. From the results it was disclosed that phosphonate derivatives (6a-f) exhibited more potent antioxidant activity than that of phosphoramidate derivatives (7a-f).
