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.

Berger G^1,2, Vilchis-Reyes M¹, Hanessian S³

• ¹Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC, H3C 3J7 (Canada) ²Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Université Libre de Bruxelles, Campus Plaine CP205/5, Université Libre de Bruxelles, Bd du Triomphe, 1050 Brussels (Belgium) ³Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC, H3C 3J7 (Canada)

http://onlinelibrary.wiley.com/doi/10.1002/anie.201506208/abstract
http://onlinelibrary.wiley.com/doi/10.1002/anie.201506208/epdf

Abstract

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 polyproline II 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 nπ* stabilization of the trans-amide conformation.