STABILIZATION OF A CIS AMIDE BOND IN A HOST-GUEST COMPLEX

Macrobicycle 12 has been synthesized and its binding properties with a range of N-acetyl amino acid carboxylates (as tetrabutylammonium salt s) have been studied. While the binding results showed little selectiv ity for the various substrates investigated, detailed NMR studies have revealed that D-amino acid substrates bind predominantly on the outsi de of the macrobicycle cavity by a strong carboxylate-thiourea interac tion, whereas L-amino acid substrates bind predominantly on the inside of the cavity also establishing a strong carboxylate-thiourea interac tion but with the acetyl amide in a cis configuration. Molecular model ing studies suggest that the energetic penalty associated with adoptin g a cis amide configuration in the host-guest complex is compensated b y intermolecular hydrogen bonds between the cis amide and the rim of t he macrobicycle.