Conformational Studies of Chiral Vinylogous Sulfonamidopeptides

The conformational preferences of chiral vinylogous aminosulfonic acids (vs‐amino acids) and of the corresponding oligomers (vs‐peptides) were investigated by a combination of X‐ray crystallography, variable‐temperature (VT) 1H NMR spectroscopy, FT‐IR spectroscopy, and NOE experiments. The major source of conformational freedom in the monomers is the rotation around the CC bond connecting the double bond with the allylic stereocenter (NC*CC). The allylic conformational preferences can be altered in the oligomers by the formation of secondary structures enforced by hydrogen bonding. Twelve‐membered‐ring hydrogen bonding is detected in the crystal structure of vs‐dipeptide 9, while fourteen‐membered‐ring hydrogen bonding is the most common folding pattern for the oligomers in chloroform solution. The experimental results are complemented by computer modeling: suitable force‐field (FF) parameters for the unsaturated sulfonamide group were developed from ab initio calculations. A Goodman–Still systematic pseudo‐Monte‐Carlo search was used for the conformational search. The conformers were minimized in chloroform with the GB/SA model. The calculations correctly predicted both the size of the hydrogen‐bonded ring and its relative importance, in agreement with the experimental data in solution.