SYNTHESIS OF PEPTIDE AMIDES USING FMOC-BASED SOLID-PHASE PROCEDURES ON 4-METHYLBENZHYDRYLAMINE RESINS

A two-step low-high protocol for the efficient synthesis of peptide am ides is described. The protocol exploits the efficiency of Reagent K f or side-chain deprotection with the capability of the hard acid triflu oromethanesulfonic acid (TFSMA) for cleavage of the peptide from the b enzhydrylamine resin. This procedure has proven to be an effective met hod for the synthesis of peptide amides. The formation of alpha-aminos uccinimide (Asu) derivatives were observed with aspartyl-containing pe ptides as a minor side reaction product of this procedure, but this As p-->Asu rearrangement could be successfully suppressed by employing lo w temperature conditions. The N- to O-acyl rearrangement of threonine and/or serine residues also only occurred to a minor extent under thes e synthetic conditions. (C) Munksgaard 1995.