Synthesis and NMDA-receptor affinity of 4-oxo-dexoxadrol derivatives.

A synthesis of novel dexoxadrol analogues is described, which allows modifications of the piperidine substructure. The key step of the synthesis is a hetero Diels-Alder reaction of the imine 12 with Danishefsky's diene 6. After separation of the diastereomeric piperidones 14a and 14b, the relative configuration of the unlike configured piperidone 15b was determined by X-ray crystal structure analysis. In receptor binding studies the like configured secondary amine 15a (racemate) showed considerable affinity toward the phencyclidine binding site of the NMDA receptor (Ki=470 nM).

Determination of L-hyoscyamine in atropine and D-hyoscyamine in L-hyoscyamine by chiral capillary electrophoresis as an alternative to polarimetry.

A method for the separation of atropine enantiomers, D- and L-hyoscyamine by capillary electrophoresis (CE) has been developed and validated. The advantages of the CE method compared with polarimetry include smaller amounts of analytes and a lower limit of detection of the unwanted enantiomer. Moreover, the present method enables a baseline separation of the analytes and tropic acid, one of the typical impurities of atropine. The developed enantioseparation of atropine was performed using a commercially available sulfated beta-cyclodextrin and was validated for the determination of L-hyoscyamine in atropine as well as for the enantiomeric purity of L-hyoscyamine.