Enantioselective recognition with C₃-symmetric cage-like receptors in solution and on a stationary phase

The chiral C₃-symmetric, cage-like receptors (S,S,S)-(+)-1 and (S,S,S)-(+)-2 with convergent, helically oriented amide hydrogen bonding sites have been prepared by a short, modular synthetic route. They are found to complex N-protected amino acid derivatives and, in particular, dicarboxylic acids in non-competitive solvents. Enantioselectivity is observed in the binding of N-Cbz-Glu (N-carbobenzyloxy-protected glutamic acid), and differences in stability of the diastereoisomeric complexes [Δ(ΔG) of up to 4.6 kJ mol^-1] have been measured by ¹H NMR binding titrations in CDCl₂CDCl₂. The geometries of free and bound receptor (S,S,S)-(+)-1 have been analysed by computer molecular modelling. Receptor (S,S,S)-(+)-2 is covalently linked to thiol-functionalised silica gel, yielding the novel chiral stationary phase (CSP) (S,S,S)-14. In analytical HPLC (high performance liquid chromatography) runs, the new CSP is found to be effective for the optical resolution of (±)-1,1′-binaphthyl-2-2′-diol derivatives, but not for the separation of enantiomeric amino acid derivatives.