GR 24 Enantiomers: Synthesis, NMR Spectroscopy, X-ray Crystallography, and Separation by Chiral Electrokinetic Capillary Chromatography

Abstract

Chiral discrimination of enantiomers of 2-methyl-4-(2-oxo-2,3,3a,8b-tetrahydro-4H-indeno[1,2b]furan-3-yl-iden emethoxy)but-2-en-4-olide (commonly referred to as GR 24) by three polymeric chiral surfactants (PCS) is studied by use of chiral polymeric surfactant capillary electrophoresis (CPSCE). The CPSCE results indicate that the optical configurations of valine residues on the PCS backbone affect chiral resolution and elution order of GR24 stereoisomers. The L- and D-forms of poly(sodium N-undecanoyl valinate) provide baseline separation of all four enantiomers while the DL-form separates diastereomers of GR 24 (1). A model is presented rationalizing the migration behavior and chiral resolution of 1 in CPSCE. The actual configuration of the stereogenic centers of GR 24 and 3-[(2,5-dihydro-3-methyl-2-oxo-5-furanyl)oxo]-methylene-3,3a,6,6a-tetrah ydro-2H-cyclopenta[b]furan-2-one (GR 7) is established by a concerted application of high-resolution nuclear magnetic resonance spectroscopy and X-ray crystallography.