An extension of the 'Bip method': induced axial chirality in a series of dipeptides based on Bip/beta(2,2)-HBip combined with Ala/beta(3)-HAla

In the search for an extension of the ‘Bip method’ for determining the absolute configuration of b-amino acids and bpeptides, dipeptides based on b2,2-HBip/L(D)-Ala, Bip/L-b3-HAla, and b2,2-HBip/L-b3-HAla were synthesized in solution and the induced circular dichroism (ICD) in their biphenyl core evaluated in comparison with the previously investigated Bip/L(D)-Ala series. Weak, poorly informative ICDs were observed in MeOH solution for the linear N-Boc protected dipeptide methyl esters based on b2,2-HBip, as well as for those with Ala/b3-HAla at the N-terminus of Bip/b2,2-HBip. However, a significant ICD was recorded for Boc-Bip-L-b3-HAla-OMe. These results were confirmed by low-temperature 1H NMR spectroscopy studies of the dipeptides in CDCl3 and CD3OD solutions, showing two diastereoisomeric conformers in significantly different populations for Boc-Bip-L-b3- HAla-OMe in CD3OD. In general, ICDs were found to be weaker for dipeptides containing b-amino acids as compared to those of their a-amino acid counterparts.