Synthesis and Structural Studies of Homooligomers of Geminally Disubstituted β2,2-Amino Acids with Carbohydrate Side Chain

A new class of geminally disubstituted C-linked carbo-beta(2,2)-amino acids (beta(2,2)-Caa) were prepared from D-glucose. The structures of homooligomeric di-, tetra-, and hexapeptides prepared from (S)-beta(2,2)-Caa were studied with NMR (in CDCl3), CD, and Molecular Dynamics calculations. These beta(2,2)-peptides have shown the presence of stable 6-membered (6-mr) NH(i)center dot center dot center dot CO(i) intra-residue H-bonded (C-6) strands. It was found that the strand structures realized in these systems were additionally stabilized by the electrostatic interaction arising due to the proximity of amide proton (NH(i)) to the oxygen of the preceding methoxy group (O(Me)(i-1)) at the C3 carbon of the carbohydrate ring. The new beta(2,2)-Caa residues with additional support to H-bonding considerably expand the domain of foldamers.