INCOMPLETE TRIFLUOROACETIC-ACID DEPROTECTION OF ASPARAGINE-TRITYL-PROTECTING GROUP IN THE VICINITY OF A REDUCED PEPTIDE-BOND

During the Fmoc solid-phase synthesis of reduced peptide bond analogue s, we observed that the trityl protection of an asparagine residue in the vicinity of a reduced peptide bond is not cleaved completely after the final trifluoroacetic acid deprotection step. The relative positi on of the Asn side-chain amine and of the aminomethylene bond as well as the preferential protonation of the secondary amine can be used to explain this phenomenon. We show that longer deprotection times or the use of methyl-trityl protection partially improves the yield of the A sn-deprotected peptide whereas xanthenyl protection totally overcomes this problem.