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 β-aminoethane sulfonylchlorides can be employed for efficient automated solid phase synthesis of β-peptidosulfonamides and β-peptidosulfonamide/β-peptide hybrids containing one or more β-peptidosulfonamide residues. Thus, Fmoc-protected β-aminoethane sulfonylchlorides 5a-c led to the hexa-β-peptidosulfonamide 9 and the nona-β-peptidosulfonamide 10. In addition, the β-peptidosulfonamide/β-peptide hybrids 13 and 16, consisting of six and nine β-residues, respectively, and containing a single β-peptidosulfo-namide unit in the middle, as well as the peptidosulfonamide/β-peptide hybrid 15 with nine β-residues, including an N-terminal β-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 β-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.