Reprint of: Enantiomeric separation of functionalized ethano-bridged Tröger bases using macrocyclic cyclofructan and cyclodextrin chiral selectors in high-performance liquid chromatography and capillary electrophoresis with application of principal compon

•Enantiomeric separation of 14 functionalized ethano-Tröger base racemates in HPLC and CE.•An example of γ-CD showing superior enantioselectivity for a class of compounds compared to β-CD.•Greater retention on the β-CD CSP shows strong inclusion is not necessary for chiral recognition.•PCA of RSP-CD, and LARIHC-RN showed that retention is governed by the size of the R1 substituent.•PCA of γ -CD, RSP-CD, and LARIHC-RN showed enantioresolution is not governed by retention.

The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs ≥ 1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC™ cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.