Incomplete TFA deprotection of N-terminal trityl-asparagine residue in fmoc solid-phase peptide chemistry.

We demonstrate that TFA deprotection of trityl-protected N-terminal asparagine is incomplete under normal conditions, resulting in low yields or impure products. This phenomenon does not occur if the asparagine is internal, nor for trityl-protected N-terminal glutamine. Studies on the deprotection of H Asn(Trt)OH show that the incomplete deprotection is due to the extremely slow removal of a trityl group close to an amino group. The use of the new methyl-trityl protecting group overcomes this problem resulting in rapid and complete deprotection.