Enantiomeric separation of precursors of Rho-kinase inhibitors by HPLC on polysaccharide-based chiral stationary phases

The separation of enantiomers of substituted cyclohexanecarboxamides, benza mides and chemical precursors of Rho-kinase inhibitors was achieved using d erivatized polysaccharide-based chiral stationary phases. Separations were by normal phase HPLC with a mobile phase Of n-hexane-alcohol (methanol etha nol or 2-propanol) in various proportions, and a silica-based cellulose tri s-3,5-dimethylphenylcarbamate (Chiralcel OD-H), tris-methylbenzoate (Chiral cel OJ), a silica-based amylose tris-(S)-1-phenylethylcarbamate (Chiralpak AS), or tris-3,5-dimethylphenylcarbamate (Chiralpak AD). The effects of con centration of various aliphatic alcohols in the mobile phase were investiga ted The effect of structural features on the discrimination between the ena ntiomers was examined. The isolation of milligram amounts of enantiomers of two derivatives was performed on an analytical column by multiple repetiti ve injections under overload conditions.