Département de chimie moléculaire

The cis/trans isomerization of peptides contg. the pseudoproline (4R)-thiazolidine-4-carboxylic acid Cys($\Psi$R1,R2 pro) is investigated from both an exptl. and a theor. point of view by NMR and DFT calcns. A series of Ac-Cys($\Psi$R1,R2 pro)-OCH3 and Ac-Cys($\Psi$R1,R2 pro)-NHCH3 peptides were prepd. to assess the influence of the substitution at the C2 position as well as of the amide following the thiazolidine residue. For each compd., the cis/trans ratio along with free energy, the puckering of the thiazolidine ring and the free rotational energy barrier are reported and discussed. We observe there is a pronounced effect of the C2 substituents and of the chirality upon the cis/trans ratio with the population of the cis content in the order (2R)-Cys($\Psi$CH3,H pro) {\textless} (2S)-Cys($\Psi$H,CH3 pro) {\textless} Cys($\Psi$CH3,CH3 pro). This is interpreted as a consequence of the steric effects imposed by the 2-methylation. For the dimethyl-substituted compds. our results revealed a destabilization of the trans conformers along with a lowering of the rotational trans to cis barrier. We also demonstrate that the introduction of Me substituents on the thiazolidine ring reduces the autocatalysis effect, and in particular that no autocatalysis occurs for the di-Me deriv. A good agreement is obtained between all our exptl. observations and our DFT calcns. It rationalizes the main effects which tailor the cis/trans isomerization. [on SciFinder(R)]