Enantiomeric resolution of the calcium channel antagonist 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane (NGP 1-01)

We report the enantiomeric resolution and results of studies designed to pr obe possible enantiospecific calcium channel activity of 8-benzylamino-8,11 -oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane (NGP 1-01), a known pol ycyclic benzylamino calcium channel antagonist. R-(-)-acetylmandeloylchlori de was used to generate the two diastereomers which were separated by conve ntional column-chromatography. Hydrolysis of the separated amide diastereom ers was achieved in 10% oxalic acid/dichloromethane with silica gel as cata lyst and yielded the resolved enantiomers of NGP 1-01. Enantiomeric purity was assessed by in situ derivatization of the individual enantiomers with 2 ,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (TAGIT) and HPLC analysis. A standard C-18 column was used and the enantiomeric purity was found to be 98.5% and 96.63% for the (+)- and the (-)-enantiomer, respectiv ely. The enantiomers exhibited similar activity profiles for calcium channe l antagonism and also did not differ from the racemic mixture, suggesting t hat NGP 1-01 has very weak or no stereo-selectivity in the calcium channel assay used.