Enantiomeric separation of epoxides using derivatized y-cyclodextrins : gas chromatographic and molecular docking studies

Abstract

Enantiomeric separations of 49 aromatic and aliphatic epoxides were studied by means of capillary gas chromatography using octakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)cyclomaltooctaose (or GSiMe) and octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)cyclomaltooctaose (or GSiAc) as chiral stationary phases. The influence of type, position, and number of substituent; position of chiral center; and main-structure of epoxides on retention and enantioselectivity was systematically investigated. Thermodynamic data and molecular docking calculation were also acquired to clarify the strength of analyte−stationary phase interaction and the mechanism of chiral recognition towards the selected groups of epoxides. All aromatic epoxides could be successfully enantioseparated with either GSiMe or GSiAc phase, or both of them. Ortho-substitution on the aromatic ring seemed to promote enantioseparation. 5hexe was the only chiral aliphatic epoxides that could be separated on GSiAc column. Generally, the GSiAc phase exhibited higher degree of enantioseparation towards most analytes than did the GSiMe phase. In addition, type, position, and number of analyte substituent as well as type of cyclodextrin substituent strongly affect enantioseparation. Among all epoxides tested, cis-2 exhibited the best enantioseparation on the GSiAc column. Results from molecular modeling of 12 mono-substituted styrene oxides and GSiAc were in agreement with those from gas chromatographic experiment and suggested that the complexation between epoxides and GSiAc were dependable on the type and position of analyte substituent.