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 ‐peptidosulfonamide 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.