SummaryTwo cholic acid derivatives have been synthesized and bonded to porous silica via a hydride-modified substrate. The supports obtained, which were characterized by differential scanning calorimetric and infrared measurements, were found to be enantioselective for a variety of analytes in normal-phase high-performance liquid chromatography. Optimization of enantiomer separations was achieved by studying the influence of mobile phase composition. The effect of substituents on the retention and resolution of hydantoins and naphthylethylamines has been evaluated. General considerations of the separation mechanism on both stationary phases are discussed.

In an effort to elucidate the mechanism of chiral discrimination of cholic acid-based stationary phases, the enantiomeric recognition ability of six chiral stationary phases (CSPs), prepared from differently substituted cholic acid derivatives, was evaluated in normal phase high-performance liquid chromatography (HPLC) with a series of 1,1'-binaphthyl compounds. The influence of structural variations of analytes on retention and enantioselectivity was investigated. Particularly high values of enantioselectivity were observed for the binaphthol enantiomers on a CSP prepared from the allyl 7 alpha,12 alpha-dihydroxy-3 alpha-phenylcarbamoyloxy-5 beta-cholan-24-oate. The complexes of this chiral selector with both enantiomers of binaphthol were studied as models for the interactions responsible for the enantioseparation with the cholic acid-based stationary phases. The 1:1 stoichiometry of the complex in solution was determined by UV titration. The chiral selector dissolved in chloroform exhibited a chiral discrimination for the binaphthol in (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopies. Some aromatic proton and carbon resonances of binaphthol were clearly separated into a pair of peaks due to enantiomers in the presence of the chiral selector. Moreover, on the basis of molecular mechanics calculation, a chiral discrimination model was proposed which nicely explains the relevant chromatographic behavior of the 1,1'-binaphthyl derivatives.

SummaryPermethylated P-cyclodextrin (hereafter designated perMe-P-CD), diluted or not in polysiloxane, is an efficient chiral discriminant for native, 3-methylated, and 1,3-dimethylated series of 5-methyl-5-(CnHzn+l)hydantoins. From thermodynamic data obtained with pure perMe-P-CD and with the aid of molecular modeling, it is concluded that: (i) For native hydantoin derivatives having a carbon chain at the 5-position varying from ethyl to nonyl (2 I n I 9), the retention time is related to their H-bonding capability. The resolution is poor for derivatives with n 5 4. For n 2 5, the resolution is considerably improved and this increase in resolution is attributed to the long alkyl chain being capable of being buried inside the cyclodextrin cavity. (ii) For 1,3-dimethylhydantoin derivatives having a carbon chain at the 5-position varying from ethyl to hexyl (2 In 16), the retention time is mainly determined by a steric fit between the solute and the inner volume of the macrocyclic cavity. For n = 2, a particular behavior is observed, consistent with a total inclusion of the solutes inside the cavity. By contrast with the native hydantoins, the selectivity is high for light derivatives. Thus, the selectivity does not correlate with a strong docking energy (such as the presence of H-bonds postulated with native derivatives). (iii) For 3-methylhydantoin derivatives having a carbon chain at the 5-POsition varying from ethyl to octyl (21 nI8), as expected, retention time and selectivity are intermediate between that of native hydantoins and 1,3-dimethylhydantoins. For all three series, where n 2 5, the increase in chain length ( n ) does not bring about substantial changes in the chromatographic results. Therefore, for these long alkyl chain derivatives, similar dominant interactions with perMe-P-CD are postulated.

An original chiral selector, namely the prop-2-enyl 3α-(N-phenylcarbamate)-7α,12α-dihydroxy-5β-cholan-24-oate, is bonded onto the silica surface by three different grafting modes. The influence of the total structure of the chiral stationary phases (CSPs) on enantioseparation is studied. These CSPs are prepared in two steps. In the first step, the silica surface is reacted with one of the following reagents: 1) (3-mercaptopropyl)trimethoxysilane, yielding a rather monomeric support, 2) chlorodimethylsilane, leading to a monomeric material, or 3) triethoxysilane, affording a polymeric packing. In the second step, the chiral selector is bonded onto the modified silica structures to provide the corresponding stationary phases SH, CDS, and TES, respectively. The CSP SH shows the poorest column performance. CSPs CDS and TES show similar mass transfer kinetics; this highlights the good behaviour of the polymeric packing. CSP TES displays globally the highest enantioselectivity and is found to be extremely stable despite its use over months. The silanization reaction with triethoxysilane provides a suitable support for chiral stationary phases. 2155

The suitability of cyclocholates as chiral selectors in gas chromatography has been evaluated. We present the synthesis and characterization of two cyclocholates, viz. 3α,7α‐diacetoxycyclo[3]cholate and 3α,7α‐diacetoxycylo[4]cholate. Mixtures of these new selectors with polysiloxanes were tested as chiral stationary phases in capillary gas chromatography. Several enantiomer separations of common racemates were achieved with the 3α,7α‐diacetoxycyclo[3]cholate at 10% in OV‐1701 (w/w). It was shown that column efficiency was strongly dependent on temperature and that enantioselectivity was very sensitive to column conditioning. This chromatographic behavior suggested that cyclocholates were only dispersed in polysiloxane. Thus, it was assumed that chiral discrimination occurred via enantioselective adsorption interactions of enantiomers at the surface of the solid chiral selector dispersed in the polysiloxane matrix OV‐1701.