Synthesis, spectral characterization, and pro- and antioxidant activity of phosphorylated derivatives of cis-tramadol

GRAPHICAL ABSTRACT

ABSTRACT

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).

KEYWORDS:

• cis-Tramadol
• phosphorylation
• pro- and antioxidant activity (LPO, NO₂⁻, total SOD, and CAT)

Funding

The author Mr. S. Rasheed is thankful to University Grants Commission (UGC), New Delhi, INDIA for providing financial support through UGC-BSR-RFSMS (Research Fellowship in Sciences for Meritorious Students) Fellowship (F.4–1/2011, BSR-RFSMS-SRD). The co-authors Mr. G. Madhava and Mr. SK. Thaslim Basha are also grateful to UGC for providing financial assistance (SRF).