Enantiomeric resolution of the calcium channel antagonist 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]unde cane (NGP 1-01).
We report the enantiomeric resolution and results of studies designed to probe possible enantiospecific calcium channel activity of 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undec ane (NGP 1-01), a known polycyclic benzylamino calcium channel antagonist. R-(-)-acetylmandeloylchloride was used to generate the two diastereomers which were separated by conventional column-chromatography. Hydrolysis of the separated amide diastereomers was achieved in 10% oxalic acid/dichloromethane with silica gel as catalyst 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 C18 column was used and the enantiomeric purity was found to be 98.5% and 96.63% for the (+)- and (-)-enantiomer, respectively. The enantiomers exhibited similar activity profiles, for calcium channel antagonism and also did not differ from the racemic mixture, suggesting that NGP 1-01 has very weak or no stereo-selectivity in the calcium channel assay used.
Malan
S F
SF
Pharmaceutical Chemistry, Potchefstroom University for CHE, South Africa.
Dockendolf
G
G
Van der Walt
J J
JJ
van Rooyen
J M
JM
van der Schyf
C J
CJ
D000818:Animals; D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D013237:Stereoisomerism
D001952:Bridged-Ring Compounds; D002121:Calcium Channel Blockers; C049649:NGP 1-01