CONFORMATIONAL STUDIES OF CHIRAL VINYLOGOUS SULFONAMIDOPEPTIDES

The conformational preferences of chiral vinylogous aminosulfonic acid s (vs-amino acids) and of the corresponding oligomers (vs-peptide) wer e investigated by a combination of X-ray crystallography, variable-tem perature (VT) H-1 NMR spectroscopy, FT-IR spectroscopy, and NOE experi ments. The major source of conformational freedom in the monomers is t he rotation around the C-C bond connecting the double bond with the al lylic stereocenter (N-C-C=C). The allylic conformational preferences can be altered in the oligomers by the formation of secondary structur es enforced by hydrogen bonding, Twelve-membered-ring hydrogen bonding is detected in the crystal structure of vs-dipeptide 9, while fourtee n-membered-ring hydrogen bonding is the most common folding pattern fo r the oligomers in chloroform solution. The experimental results are c omplemented by computer modeling: suitable force-field (FF) parameters for the unsaturated sulfonamide group were developed from ab initio c alculations. A Goodman-Still systematic pseudo-Monte-Carlo search was used for the conformational search. The conformers were minimized ill 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.