Cyclodextrin-based liquid chromatographic enantiomeric separation of chiral dihydrofurocoumarins, an emerging class of medicinal compounds

• Published in: Journal of Chromatography A 2003-09, Vol.1011 (1), p.37-47
• Main Authors: Schumacher, Douglas D., Mitchell, Clifford R., Xiao, Tom L., Rozhkov, Roman V., Larock, Richard C., Armstrong, Daniel W.
• Format: Article
• Language: English
• Subjects: Analysis; Analytical chemistry; Biological and medical sciences; Chemistry; Chromatographic methods and physical methods associated with chromatography; Coumarins - chemistry; Coumarins - isolation & purification; Cyclodextrins; Cyclodextrins - chemistry; Dihydrofurocoumarins; Exact sciences and technology; Furans - chemistry; Furans - isolation & purification; General pharmacology; Medical sciences; Other chromatographic methods; Pharmacology. Drug treatments; Stereoisomerism
• ISSN: 0021-9673
• DOI: 10.1016/S0021-9673(03)01128-2

A set of 28 racemic dihydrofurocoumarins in which the stereogenic center is located in the furan ring have been synthesized. Currently no effective asymmetric synthesis of this class of compounds exists, although their enantiomers are produced biologically by certain plants. Their diverse medicinal properties are being investigated in several laboratories. The enantioselective separation of these dihydrofurocoumarins by three native and six derivatized cyclodextrins has been evaluated in the reversed-phase mode, the polar organic mode, and normal-phase mode. The hydroxypropyl-β-cyclodextrin is the most effective chiral stationary phase (CSP) at separating the dihydrofurocoumarins into enantiomers, showing some enantioselectivity for 22 dihydrofurocoumarins, and baseline resolving 16 of the 28 compounds in the reversed-phase mode. The acetyl-β-cyclodextrin and 2,3-dimethyl-β-cyclodextrin also showed enantioselectivity for a large number (18 and 17, respectively) of dihydrofurocoumarins in the reversed-phase mode. The native cyclodextrins are ineffective and the aromatic derivatized β-cyclodextrins are only marginally effective at separating the furocoumarin enantiomers in the reversed-phase mode. The polar organic mode and the normal-phase mode have also been evaluated with these CSPs, but no enantioseparations were observed.