GEOMETRICAL OPTIMIZATION OF 1,1'-BINAPHTHALENE RECEPTORS FOR ENANTIOSELECTIVE MOLECULAR RECOGNITION OF EXCITATORY AMINO-ACID DERIVATIVES

A series of optically active 1,1'-binaphthalene-derived receptors with N-(pyridine-2,6-diyl)acetamide [CONH(py)] H-bonding sites in the 6,6' -positions has been prepared for the enantioselective complexation of the N-carbobenzyloxy (Cbz)-protected excitatory amino acids aspartic ( Asp) and glutamic (Glu) acid via two COOH...CONH(py) H-bonding arrays and additional secondary bonding interactions. The conformational homo geneity of the receptors is enhanced by locking the dihedral angle the ta about the chirality axis through the C(1)-C(1') bond of the 1,1'-bi naphthalene moiety either by bridging the 2,2'-positions or by attachi ng bulky substituents to these centres, Computer modelling has shown t hat bridging is more efficient in locking this dihedral angle than the introduction of bulky substituents, and these predictions have been c onfirmed by H-1 NMR binding studies in CDCl3 and in CDCl3-CD3OD 99.8:0 ,2, Plots of the enantioselectivity Delta(Delta G degrees) (difference in stability between diastereoisomeric complexes) in the recognition by the bridged receptors as a function of the enforced dihedral angle theta are peak-shaped, and the highest values have been measured in CD Cl3 (300 K) for the complexation of the enantiomers of N-Cbz-Asp [Delt a(Delta G degrees) = 6.9 kJ mol(-1)] and N-Cbz-Glu [Delta(Delta G degr ees) = 5.2 kJ mol(-1)] by (R)-21 (theta = 86 +/- 4 degrees), The more stable diastereoisomeric complexes are highly structured, and tight ho st-guest bonding has been confirmed by the observation of up to five, intermolecular NOEs. Enforcing the conformational homogeneity by bridg ing represents a new general principle for improving the chiral recogn ition potential of 1,1'-binaphthalene receptors.