Effective resolution of racemic pirlindole at the preparative scale

Pirlindole, a racemic antidepressant drug, was recently resolved using the derivatization method coupled with preparative HPLC. In order to improve th is technique, the use of amino acid derivatives as chiral derivatizing agen ts (CDA) was investigated. Among different residues, the (L)-phenylalanine methyl ester was found to be very effective to separate pirlindole enantiom ers using a medium pressure liquid chromatographic (MPLC) method. This proc edure is better adapted to preparative application than HPLC. Thus, several grams of the pirlindole antipodes were isolated and characterized. These t wo enantiomers permitted the study of the stereochemical influence at the p harmacological level. Chirality 11.261-266, 1999. (C) 1999 Wiley-Liss, Inc.