ANALYTICAL AND PREPARATIVE ENANTIOMERIC SEPARATION OF A SERIES OF C5-CYCLOALKYLAMINE-1,4-BENZODIAZEPIN-2-ONE CCKB RECEPTOR ANTAGONISTS BY CHIRAL HPLC

A series of C5 cycloalkyl benzodiazepin-2-one CCKB receptor antagonist s are reported in which substitution by tolyl-urea at C3 has generated a chiral centre. As only one of these enantiomers is selective for th e CCKB receptor an analytical separation of the enantiomers was develo ped to monitor the resolution of compounds by chemical means. It was s hown that such compounds may be resolved using a Pirkle-type 3,5-(dini trobenzoyl)-leucine (DNBL) chiral stationary phase (CSP) to give high alpha and R(S) values. Such high enantioselectivities allowed the sepa ration to be scaled-up sufficiently such that gram quantities of each enantiomer could be isolated by preparative chiral HPLC. An investigat ion is described in which the effect of substituent, mobile phase comp osition, temperature and the alternate CSP 3,5-(dinitrobenzoyl)-phenyl glycine (DNPBG) is discussed for such compounds.