HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF THE ISOMERICPURITY OF A SERIES OF DIOXOLANE NUCLEOSIDE ANALOGS

Racemic (+/-)-cis-2 hydroxymethyl-4-(cytosin-1'-yl)-1,3-dioxolane anal ogue (BCH-204) exhibited high levels of anti-HIV activity, but also sh owed cytotoxicity at the active concentration. To examine the possibil ity of enantiomerically separating the HIV activity from the cytotoxic ity in the dioxolane nucleosides, high-performance liquid chromatograp hy using chiral stationary phase columns was examined. The successful separation of dioxolane compounds was demonstrated utilizing optimum c onditions of columns, solvents, flow-rates and temperature. In the rev ersed-phase mode, the cyclodextrin columns Cyclobond I SP and RSP were used to separate the enantiomers of cis- and trans-(+/-) dioxolane-C , and the protein column alpha-AGP was successful in separating enanti omerically cis-(+/-) dioxolane-G and cis- and trans-enantiomeric forms of (+/-)-dioxolane-A. In the normal-phase mode, one of the cellulose columns, Chiralcel OJ, successfully separated enantiomerically (+/-)-d ioxolane-T nucleosidic analogue.