ISSN:
0899-0042
Keywords:
oxazepam
;
demoxepam
;
3-O-acyl-1-(N,N-dimethylcarbamyl)oxazepam
;
1-(N,N-dimethylcarbamyl)oxazepam
;
3-O-(N,N-dimethylcarbamyl)oxazepam
;
camazepam
;
norcamazepam
;
1,3-O-bis(N,N-dimethylcarbamyl)oxazepam
;
kinetics of racemization
;
enantioselectivity of esterases
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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 (t½ 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.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530030313
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