Development and Conformational Analysis of a Pseudoproline-Containing Turn Mimic

The liquid-phase synthesis and the conformational analysis of a small library of fully protected tetramers containing L-pyroglutamic acid (L-pGlu), (4S,5R)-4-methyl-5-carboxybenzyloxazolidin-2-one (L-Oxd), or (4R,5S)-4-methyl-5-carboxybenzyloxazolidin-2-one (D-Oxd) as residue i + 1 are reported to test the tendency of these oligomers to assume a -hairpin conformation. The most promising molecule is Boc-L-Val-D-Oxd-Gly-L-Ala-OBn, which assumes a preferential -turn conformation in CDCl3, as shown by IR and 1H NMR analysis. These findings have been confirmed by DFT calculations, which provide an interpretation for the available experimental data and agree with the reported observations.