γ‐Cyclodextrin as chiral mobile phase additive in the HPLC separation of the atropisomers of some N‐arylthiazoline‐2‐thiones and N‐arylthiazoline‐2‐ones: Attempts to quantify the effect of selected structural parameters

Abstract

The effect of the position and type of the substituent on the chromatographic separation of N-arylthiazoline-2-thione and arylthiazoline-Zone atropisomers are described in reversed-phase HPLC using p-or y-cyclodextrin as chiral mobile phase additive.A quantitative approach to experimental design has been developed.o 1993 Wiey-Liss, Inc.KEY WORDS: chiral additive, cyclodextrin, RP-HPLC, atropisomers, experimental design a-, p-, and y-cyclodextrins (CDs) are cyclic, nonreducing oligosaccharides consisting of, respectively, 6, 7, and 8 units bonded through a-1,4 M a g e s , which can be represented schematically as a truncated cone. The interior of CD cavities is relatively hydrophobic, being formed by a circular codguration of hydrogen atoms and glucoside oxygen atoms, while all the hydroxyl groups are on the outside of the molecule. The wider side of CD cavity contains secondary hydroxyl groups, while the opposite smaller opening is occupied by primary hydroxyl groups. This arrangement explains the ability of CDs to form inclusion complexes in aqueous solutions. Therefore, they have been used for the separation of geometric, structural, and stereoisomers by thin-layer chromatography (TLC), l3 high-performance liquid chromatography (HPLC), kg and gas chromatography (GC). l'-lz Two different approaches have been designed for the use of CDs in HPLC, the use of chemically bonded CD-silica stationary and the application of CD as mobile phase components of reversed-phase (RP) systems. [20][21][22] Since chiral glucose units form the cyclodextrin cavity, the cavity functions as a chiral selector and CDs are especially useful for the chromatographic separation of enantiomers.The parameters of such a separation are mainly influenced by the stability of the inclusion complexes formed with each enantiomer and as a consequence by the intrinsic structural features of the molecule. Factors which influence the chiral recognition mechanism when p-or y-CD is used in HPLC as a chiral mobile phase additive are still poorly understood. An empirical procedure that uses molecular structure to predict the enantioselectivity of derivatized p-CD bonded stationary phases has been developedz3 for compounds which have four substituents on a stereogenic center. In this paper, we have applied a different approach, namely a two-level full factorial design to quantify the effect of three selected structural parameters (factors) on 0 1993 Wiley-Liss, lnc.the separation and capacity factors (responses) of atropisomers of some N-aryl-substituted heterocycles (Fig. 1) by HPLC using an achiral stationary phase and CDs as mobile phase additives. MATERIAL AND METHODS Chemicals and ReagentsThe synthesis of compounds 1 to 8 (Fig. 1) has been already described, together with their barriers to rotation around the pivot Acetic acid (Carlo Erba) and triethylamine (TEA, Janssen) were purchased. EtOH/H20 (955) was purified by distillation. CDs were obtained from Roquette Freres (Lestrem, France). Chromatography

Racemic drug resolution: a comprehensive guide

“…Recently, different types of CSPs, CMPAs, and their effect on enantioseparation have been discussed in the literature. [55][56][57][58] 2.3.1.2. Chiral stationary phases (CSPs).…”