Solution conformations of some azetidine cyclic peptides

The 1H‐nmr spectra (270 MHz) of cyclic di‐ and tri‐L‐azatidine‐2‐carboxylic acid [cy‐clo(L‐Aze)2 and cyclo(L‐Aze)3] were determined in CDCl3 and D2O and computer simulated. The spectral results were compared with those obtained with cyclo (L‐Pro)2 and cyclo (L,‐Pro)3. In CDCl3 and D2O solution, the four membered ring of cyclo (L‐Aze)2 is puckered with the α‐proton in a pseudo‐axial position, and the ϕ angle is smaller in absolute value than −60°, as found for cyclo (L‐Pro)2,. The puckering of the four‐membered ring of cyclo(L,‐Aze)3 in CDCl3 has the α‐proton in a pseudo–equatorial position and ϕ angle larger in absolute value than −60°, in agreement with cyclo(L‐Pro)3. In D2O, cyclo(L‐Aze)3 was found to interconvert rapidly between different conformers. In the azetidine cyclic peptides studied, the range of values found for the ϕ angles was smaller than in the related proline cyclic peptides, indicating greater rigidity in the four‐membered ring.