The Enantiomeric Separation of Tetrahydrobenzimidazoles Cyclodextrins‐ and Cyclofructans

Abstract

High performance liquid chromatography (HPLC) and capillary electrophoresis (CE) were used to examine the enantiomeric separation of a series of 17 racemic tetrahydrobenzimidazole analytes. These compounds were prepared as part of a synthetic program directed towards a select group of pyrrole-imidazole alkaloids. This group of natural products has a unique framework of pyrrole- and guanidine-containing fused rings which can be constructed through the intermediacy of a tetrahydrobenzimidazole scaffold. Several bonded cyclodextrin- (both native and derivatized) and derivatized cyclofructan-based chiral stationary phases were evaluated for their ability to separate these racemates via HPLC. Similarly, several cyclodextrin derivatives and derivatized cyclofructan were evaluated for their ability to separate this set of chiral compounds via CE. Enantiomeric selectivity was observed for the entire set of racemic compounds using HPLC with resolution values up to 3.0. Among the 12 different CSPs, enantiomeric recognition was most frequently observed with the Cyclobond RN and LARIHC CF6-P, while the Cyclobond DMP yielded the greatest number of baseline separations. Fifteen of the analytes showed enantiomeric recognition in CE with resolution values as high as 5.0 and hydroxypropyl-γ-cyclodextrin was the most effective chiral additive.

Enantioseparation with liquid membranes

“…Enantioselectivites of up to 3.0 for HPLC and 5.0 for CE were measured and hydropropyl‐γ‐cyclodextrin was found to be the most effective chiral additive investigated . Working with CE as well, Szabό et al .…”

Synergistic enantioseparation systems with either cyclodextrins or cyclofructans and L‐alanineTertbutyl ester lactate

“…The type of the substituent and the degree of substitution have proven to be a determining step in enantiorecognition . On the other hand, the utilization of CFs and their derivatives as CSs in CE is limited, and this is demonstrated by the low number of publications . Native CFs did not demonstrate any significant enantioselectivity, while their derivatives have successfully been applied as CSs in CE .…”

Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases

“…ENREF 9 In this study, three functionalized cyclofructan CSP's were evaluated for use as HPLC CSP's. The first, the LARIHC CF6-P (isopropylcarbamate derivatized cyclofructan-6) has shown exceptional selectivity for racemates with a primary amine moiety[30] while the LARIHC CF6-RN (R-napthyethylcarbamate derivatized cyclofructan-6) and LARIHC CF7-DMP (dimethyphenylcarbamate derivatized cyclofructan-7) CSP's have shown broad selectivity and applicability for a variety of classes of molecules[31 -35]. …”