N-methyl peptides. III. Solution conformational study and crystal structure of N-pivaloyl-L-prolyl-N-methyl-N'-isopropyl-L-alaninamide.

The study of tBuCO-L-Pro-Me-L-Ala-NHiPr (1) by i.r. and n.m.r spectroscopies has indicated that the middle amide group accommodates preferentially the cis arrangement in inert (CCl4) and aprotic (DMSO) solvents. Cis conformers are folded by a strong intramolecular hydrogen bond involving both terminal CO and NH groups whereas the minor trans conformers accommodate an open conformation. The cis folded form is retained in the solid state and its crystal structure was fully characterized by X-ray diffraction.