Chiral gas chromatographic separation of 2-oxabicyclo[3.3.0]octane derivatives and their synthetic precursors.

Abstract

Chiral GC separation of (+/-)-2-allyl-2-carboethoxycyclopentanone (9) and the alcohols (+/-)-3-(hydroxymethyl)-5-carboethoxy-2-oxabicyclo[3.3.0]octane (7), (+/-)-2-allyl-2-carboethoxycyclopentanol (8), and their acetylated and trifluoroacetylated derivatives were investigated on three derivatized beta-cyclodextrins (CDs) diluted in SE-54 or 1701-OH: 2,3,6-tri-O-methyl-beta-CD (PMCD); 2,3-di-O-methyl-6-O-(tert-butyldimethylsilyl)-beta-CD (DIMETBCD); 2,3-di-O-acetyl-6-O-(tert-butyldimethylsilyl)-beta-CD (DIACTBCD). The understanding of these chiral separations is extremely relevant, since cyclopentanic and bicyclic cyclopentanic rings are common structural features of many important natural products and new pharmaceutical drugs. In general DIMETBCD diluted in SE-54 showed the best chiral resolution to alcohols 7 and 8 and only DIACTBCD showed enantioselectivity to 9. Hydrogen bonds prediction and dipole moments data were obtained by molecular modeling calculations for 7ab and 8ab and Ac and TFA derivatives. Comparison of these data with the chromatographic parameters for the related compounds were used to explain the differences of their elution orders and diastereo- and enantiomeric separations on the above chiral stationary phases (CSPs). The results suggest that the CSPs enantioselectivities are not affected by the carboethoxy-functionalized cyclopentanic and bicyclic cyclopentanic rings themselves but mainly by the functional group on the other stereogenic center.