A new base-catalyzed cleavage reaction for the preparation of protected peptides

A new base-catalyzed elimination reaction employing the hindered, non-nucleophilic bases tetramethylguanidine or 1,8-diazabicyclo-[5.4.0.]undec-7-ene has been developed for the removal of protected peptides from a 2-[4-(hydroxymethyl)phenyl-acetoxy]propionyl-resin. The proposed reaction mechanism involved cleavage of the ester bond between the peptide and resin via a base-catalyzed elimination. The protected peptide-resin cleavage reaction is mild, rapid and proceeds in good yield with a very simple work- up procedure. Four protected peptide-resins varying in size from seven to sixteen residues were prepared using the 2-[4-(hydroxymethyl)phenyl-acetoxy]- propionyl-resin and then cleaved in the protected form to demonstrate the utility of the new cleavage technique. The protected peptide cleavage products can be used in the preparation of larger peptides by fragment condensation.