Structural Properties and Stereochemically Distinct Folding Preferences of 4,5-cis and trans-Methano-L-Proline Oligomers: The Shortest Crystalline PPII-Type Helical Proline-Derived Tetramer

The synthesis, structural properties, and folding patterns of a series of L-proline methanologues represented by cis- and trans-4,5-methano-L-proline amides and their oligomers are reported as revealed by X-ray crystallography, circular dichroism measurements, and DFT calculations. We disclose the first example of a crystalline tetrameric proline congener to exhibit a polyprolineII helical conformation. Experimental evidence of PPII-type helical arrangement (both in solution and in the solid state) of cis-4,5-methano-L-proline oligomers is supported by theoretical calculations reflecting the extent of n* stabilization of the trans-amide conformation.