1. 2-Chlorotrityl chloride resin. Studies on anchoring of Fmoc-amino acids and peptide cleavage
K Barlos, O Chatzi, D Gatos, G Stavropoulos Int J Pept Protein Res. 1991 Jun;37(6):513-20.
The esterification of 2-chlorotrityl chloride resin with Fmoc-amino acids in the presence of DIEA is studied under various conditions. High esterification yields are obtained using 0.6 equiv. Fmoc-amino acid/mmol resin in DCM or DCE, in 25 min, at room temperature. The reaction proceeds without by product formation even in the case of Fmoc-Asn and Fmoc-Gln. The quantitative and easy cleavage of amino acids and peptides from 2-chlorotrityl resin, by using AcOH/TFE/DCM mixtures, is accomplished within 15-60 min at room temperature, while t-butyl type protecting groups remain unaffected. Under these exceptionally mild conditions 2-chlorotrityl cations generated during the cleavage of amino acids and peptides from resin do not attack the nucleophilic side chains of Trp, Met, and Tyr.
2. The 2-chlorotrityl resin: a worthy addition to the medicinal chemist's toolbox
W J Hoekstra Curr Med Chem. 2001 May;8(6):715-9. doi: 10.2174/0929867013373192.
The polystyrene-based 2-chlorotrityl resin was originally used in the synthesis of peptides using an Fmoc-amino acid/carboxyl-linked protocol. While traditionally employed to prepare a number of biologically active peptides, the resin has received increasing attention as a support for the synthesis of pseudopeptide and non-peptide molecules recently. This review focuses on 2-chlorotrityl resin-supported synthesis of small molecules that collectively display a broad range of biological activities.
3. Use of the 2-chlorotrityl chloride resin for microwave-assisted solid phase peptide synthesis
Matthaia Ieronymaki, et al. Biopolymers. 2015 Sep;104(5):506-14. doi: 10.1002/bip.22710.
A fast and efficient microwave (MW)-assisted solid-phase peptide synthesis protocol using the 2-chlorotrityl chloride resin and the Fmoc/tBu methodology, has been developed. The established protocol combines the advantages of MW irradiation and the acid labile 2-chlorotrityl chloride resin. The effect of temperature during the MW irradiation, the degree of resin substitution during the coupling of the first amino acids and the rate of racemization for each amino acid were evaluated. The suggested solid phase methodology is applicable for orthogonal peptide synthesis and for the synthesis of cyclic peptides.
