Resolution of some 4-benzofurazanyl and 4-benzofuroxanyl 1,4-dihydropyridine derivatives by chiral HPLC on Whelk-O1 and some polysaccharide chiral stationary phases

The chromatographic chiral resolution of racemic methyl 1,4-dihydro-2,6-dim ethyl-5-nitro-4-benzofurazanyl-3-carboxylates 1 and 2 and their benzofuroxa nyl analogues 3 and 4 were studied on Whelk-Ol, Chiralcel OD-H, Chiralcel O J, and Chiralpak AD and AS. These CSPs were selected on the basis of the re sults of structural searches in Chirbase, Examination of the data and clust er analysis pointed out the influence of benzofurazane-benzofuroxane change versus alpha-beta connection change on retention and enantioselectivity, r espectively. The major contribution to the retention change arose from the type of heterocycle, whereas the major contribution to the enantioselectivi ty change came from the mode of connection (alpha or beta) almost Irrespect ive of the nature of the heterocycle. It resulted ina similarity of behavio ur between 1 and 2 on one hand and 3 and 4 on the other as far as capacity factors were concerned, and in a similarity of behaviour between 1 and 3 on the one hand and 2 and 4 on the other as far as enantioselectivities were concerned. Chiralpak AS was selected for semipreparative resolution of the enantiomers. The study of several CSPs allowed us to obtain correlations of structure with retention and enantioselectivity as well as the choice of a semipreparative support to provide the quantities for biological tests. (C ) 1999 Wiley-Liss,Inc.