A method for stabilizing the cis prolyl peptide bond: influence of an unusual n¡ú¦Ð<sup>?sup> interaction in 1,3-oxazine and 1,3-thiazine containing peptidomimetics
文摘
The cis/trans isomer ratios of the Xaa-Pyr (Pyr = pyrrolidine) 3¡ã amide bonds are significantly high (¡«90 % cis) in the novel peptidomimetics where Pyr contains 1,3-oxazine (Oxa) or 1,3-thiazine (Thi) at its 2 position. We find that an unusual n¡ú¦Ð<sub>i?1sub><sup>?sup> interaction, selectively stabilizes the cis conformer and the n)(n repulsion destabilizes the trans conformer of these molecules. Both these electronic effects oppose the steric effects in the 3¡ã amide bond. The structural requirements for manifestation of these electronic effects are determined.