Automated solid-phase synthesis and structural investigation of β-peptidosulfonamides and β-peptidosulfonamide/β-peptide hybrids:: β-peptidosulfonamide and β-peptide foldamers are two of a different kind

Fmoc-protected beta-aminoethane sulfonylchlorides can be employed for efficient automated solid phase synthesis of beta-peptidosulfonamides and beta-peptidosulfonamide/beta-peptide hybrids containing one or more beta-peptidosulfonamide residues. Thus, Fmoc-protected beta-aminoethane sulfonylchlorides 5a - c led to the hexa-beta-peptidosulfonamide 9 and the nona-beta-peptidosulfonamide 10. In addition, the beta-peptidosulfonamide/beta-peptide hybrids 13 and 16, consisting of six and nine beta-residues, respectively, and containing a single beta-peptidosulfonamide unit in the middle, as well as the peptidosulfonamide/beta-peptide hybrid 15 with 9 beta-residues, including an N-terminal beta-peptidosulfonamide residue, were synthesized by automated solid-phase synthesis. Both CD and NMR spectroscopic measurements did not indicate any helical secondary structure for 9 and 10. As was shown by CD-measurements, the beta-peptidosulfonamide residue in the hybrids 13, 15 and 16 acts as a helix breaker, especially when located in the middle of the hybrid chain (13 and 16), but, although to a lesser extent, also at the N-terminus.