Optical resolution of benzodiazepine esters by HPLC.
The separation of the enantiomers of 11-26 esters of oxazepam 1, temazepam 2, lorazepam 3 and lormetazepam 4 whith the acids benzoic 6, 2-methyl-3-nitrobenzoic 7, cynnamic 8 and hydrocynnamic 9 by HPLC on analytical columns with chiral stationary phases of (R)-N-(3,5-dinitrobenzoyl)phenylglycine (R)-DNBPG and (S)-N-(3,5-dinitrobenzoyl)leucine (S)-DNBL was described. The diastereoisomeric mixtures of esters 27-30 of the overmentioned benzodiazepines with (S)(+)-2-(6-methoxy-2-naphthyl)propionic acid have been also separated by HPLC on analytical column of SiO2. Some of the best separations have been repeated on semipreparative scale in order to isolate and characterize the optically pure enantiomers or diastereoisomers. Configurational assignment and elution order are established by a chiral recognition model. On the basis of the study by molecular models of the interaction between solute and chiral stationary phases, the conformers more interacting with these phases have been individuated and it has been possible to conclude that for any enantiomers couple the (S) isomer is always more retained by the chiral stationary phase of (R)-DNBPG and the (R) isomer by (S)-DNBL. Regarding to the interaction of diastereoisomeric esters 27-30 with SiO2, the esters more retained should result those of the benzodiazepines having (S) configuration.
Azzolina
O
O
Dipartimento di Chimica Farmaceutica, Università di Pavia.
Ghislandi
V
V
Vercesi
D
D
D001569:Benzodiazepines / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D004952:Esters / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D004952:Esters; D001569:Benzodiazepines