RESOLUTION OF O-4-(4'-DIETHYLAMINO-1'-METHYLBUTYL)AMINOQUINOLINE (CHLOROQUINE) INTO ITS ENANTIOMERS

Evidence is accumulating that 7-chloro-4-[4-diethylamino-1-methylbutyl ] amino quinoline (chloroquine) displays considerable stereoselectivit y in its metabolism, pharmacokinetics, macromolecular interactions, an d biological activity. The availability of the enantiomers has been ha mpered by the failure of direct methods of resolution. We now describe a successful resolution in which the atropisomeric 1,1'-binaphthyl-2, 2'-diyl hydrogen phosphate is used in a 1:1 ratio to form stereoselect ively the 2:1 diastereomeric salt from one enantiomer of the base, lea ving the other in solution. By this means both enantiomers of chloroqu ine may be readily isolated.