Conformational Studies on a Medium Size Cyclopseudopeptide Containing the Oxazolidin-2-one Moiety

An efficient synthesis of a 24 pseudopeptide membered ring in solution is reported in good yield. The cycle contains four units, all formed by an alpha-amino acid (Xaa) and a 4-carboxy-5-methyl-oxazolidin-2-one group (4-carboxy-5-methyl-oxazolidin-2-one = Oxd) in the same configuration (L or D). In the final sequence, the four LL or DD units are alternated so that, after cyclization, cyclo-(L-Xaa-L-Oxd-D-Xaa-D-Oxd-L-Xaa-L-Oxd-D-Xaa-D-Oxd) is formed The conformational analysis of this compound has been performed by means of IR and 1H NMR spectroscopy and shows that the CHalpha hydrogens of the alpha-amino acids retain the very deshielded chemical shifts recorded in the spectra of the free precursors. Furthermore the NH hydrogens have a weak tendency to form cross peaks, thus suggesting that the cycle lies in a large circle able to host small molecules, thus this compound is a promising candidate for drug delivery studies.