Impact of substituents on the enantioseparation of racemic 2-amidotetralins on polysaccharide stationary phases .1. Chiralcel OD

The direct enantiomeric separation of 32 racemic 2-amidotetralins on the commercially available tris-(3,5-dimethylphenylcarbamate) derivative of cellulose, coated on silica gel (Chiralcel OD), is presented. To date, the selection of a column for the chiral separation of a racemic mixture is done empirically. Studying the impact of small changes in the chemical structure of a series of amidotetralins on the separation behavior may help to give an insight in the chiral recognition mechanism. The amidotetralins differed structurally in three of their substituents, which were never directly located on the chiral carbon atom. The enantiomers of 24 out of 32 amidotetralins could be resolved with a resolution >1.5. Hydrogen bonding and pi-pi interactions are supposed to be the major analyte-chiral stationary phase (CSP) interactions. However, the spatial arrangement of the enantiomers may play an important role too. Increasing the bulkiness of the acyl substituent led to an increase in the resolution (R(s)), whereas a more bulky substituent on the aromatic ring resulted in a very low resolution. The introduction of a chlorine atom into the acyl substituent additionally increased the resolving power. (C) 1997 Wiley-Liss, Inc

Preparation of (S)-(+)- and (R)-(-)-8-trifluoromethanesulfonyloxymianserin

8-Trifluoromethanesulfonyloxymianserin (3) was synthesized. Its enantiomers were separated by means of HPLC using a chiral stationary phase in the semipreparative mode (100 mg scale) in greater than or equal to 99% optical purity. Reduction of the enantiomers of 3 under catalytic hydrogenation conditions gave the mianserin enantiomers in high purity. The absolute configuration of the enantiomers of 3 were assigned by comparing their respective optical rotations with those of the mianserin enantiomers

Direct enantiomeric separation of mianserin and 6-azamianserin derivatives using chiral stationary phases

The direct enantiomeric separation of mianserin and 6-azamianserin and some of their derivatives, respectively, by means of HPLC using two different chiral selectors was investigated. For the cellulose-based Chiralcel OD column, a strong dependence of be lipophilicity of the compounds tested on the retention behaviour was observed. To some extent, this was also found for the enantiomeric separation on the amylose-based Chiralpak AD column. In some cases a complementary behaviour of these two phases was observed: racemic mixtures that could not be separated by one column could be resolved by the other one. (C) 1998 Elsevier Science Ltd