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N , N ‐dimethylcarbamyl derivatives of oxazepam
Author(s) -
Yang Shen K.,
Lu XiangLin
Publication year - 1991
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530030313
Subject(s) - oxazepam , chemistry , enantiomer , racemization , circular dichroism , stereochemistry , chromatography , biochemistry , receptor , benzodiazepine
Three N , N ‐dimethylcarbamyl derivatives of oxazepam {1‐( N , N ‐dimethylcarbamyl)oxazepam, 3‐ O ‐( N , N ‐dimethylcarbamyl)oxazepam, and 1,3‐ O ‐bis( N , N ‐dimethylcarbamyl)oxazepam} and a 3‐ O ‐acyl‐1‐( N , N ‐dimethylcarbamyl)‐oxazepam were synthesized from either oxazepam or demoxepam. Enantiomeric pairs of these derivatives and of camazepam were resolved by high‐performance liquid chromatography on at least two of three commercially available chiral stationary phase columns employed. Absolute configurations of resolved enantiomers were established by comparing their circular dichroism spectra to those of enantiomeric oxazepams with known absolute stereochemistry. Similar to those of oxazepam, enantiomers of 1‐( N , N ‐dimethylcarbamyl)oxazepam undergo rapid racemization ( t ½ 1.9 min at 23°C and 0.9 min at 37°C) in an aqueous solution at pH 7.5. The (R)‐enantiomer of rac‐3‐ O ‐acyl‐1‐( N , N ‐dimethylcarbamyl)oxazepam was hydrolyzed ∼4.6‐fold faster than the (S)‐enantiomer by esterases in rat liver microsomes, whereas the (S)‐enantiomer was hydrolyzed ∼43‐fold faster than the (R)‐enantiomer by esterases in rat brain S9 fraction.