1. The kinetics of the removal of the N-methyltrityl (Mtt) group during the synthesis of branched peptides
D Li, D L Elbert J Pept Res. 2002 Nov;60(5):300-3. doi: 10.1034/j.1399-3011.2002.21018.x.
The purpose of this short communication is to describe the reaction rate for the removal of the N-methyltrityl (Mtt) protecting group that is used in solid-phase peptide synthesis for the production of branched and cyclic peptides. The reaction rate was observed to follow zero-order kinetics, and we suggest the optimal conditions for the removal of the Mtt group in batchwise synthesis.
2. Novel N omega-xanthenyl-protecting groups for asparagine and glutamine, and applications to N alpha-9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis
Y Han, N A Solé, J Tejbrant, G Barany Pept Res. 1996 Jul-Aug;9(4):166-73.
The N alpha-9-fluorenylmethyloxycarbonyl (Fmoc), N omega-9H-xanthen-9-yl (Xan), N omega-2-methoxy-9H-xanthen-9-yl (2-Moxan) or N omega-3-methoxy-9H-xanthen-9-yl (3-Moxan) derivatives of asparagine and glutamine were prepared conveniently by acid-catalyzed reactions of appropriate xanthydrols with Fmoc-Asn-OH and Fmoc-Gln-OH. The Xan and 2-Moxan protected derivatives have been used in Fmoc solid-phase syntheses of several challenging peptides: a modified Riniker's peptide to probe tryptophanalkylation side reactions, Briand's peptide to assess deblocking, at the N-terminus and Marshall's ACP (65-74) to test difficult couplings. Removal of the Asn and Gln side-chain protection occurred concomitantly with release of peptide from the support, under the conditions for acidolytic cleavage of the tris(alkoxy)benzylamide (PAL) anchoring linkage by use of trifluoroacetic acid/scavenger mixtures. For each of the model peptides, the products obtained by the new protection schemes were purer than those obtained with N omega-2,4,6-trimethoxybenzyl (Tmob) or N omega-triphenylmethyl (Trt) protection for Asn and Gln.
3. Incomplete TFA deprotection of N-terminal trityl-asparagine residue in fmoc solid-phase peptide chemistry
M Friede, S Denery, J Neimark, S Kieffer, H Gausepohl, J P Briand Pept Res. 1992 May-Jun;5(3):145-7.
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.
