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.

A Glimpse of Recent Developments in Brazilian Analytical Chemistry

“…Gas chromatography theoretical advances were a matter of concern in the early 1960s (Costa-Neto et al 1964), the introduction of High Resolution Gas Chromatography (HRGC) with all new concepts devised by the Grob family in Switzerland in the late 1970s early 1980s were immediately transferred to Brazil in 1981 (Furtado and Cardoso 1984;Grob 1985;Aquino Neto and Cardoso 1985), as well as Chiral-HRGC (Ramos et al 2000) and High Temperature-HRGC (Pereira et al 2004a). Recently, the new frontier of gas chromatography was also brought to Brazil, namely, The comprehensive GC Â GC (Silva-Junior et al 2007, Silva-Junior et al 2008Caramão et al 2007).…”

Chiral Separations

“…Complete separation of methamphetamine enantiomers by GC/ MS was achieved using trifluoroacetic derivatization and a β-Dex225 capillary column (99). Chiral GC separation of 2-oxabicyclo[3.3.0]octane derivatives and their precursors was investigated on three derivatized β-CD CSPs, 2,3,6-tri-O-methyl-β-CD, 2,3-di-O-methyl-6-O-(tert-butyldimethylsilyl)-β-CD, and 2,3-di-O-acetyl-6-O-(tert-butyldimethylsilyl)β-CD (100). The GC enantioseparation of atropisomeric PCBs was evaluated using modified CDs as chiral phases, and separation of enantiomers on mixed chiral selectors was also attempted (101).…”