Trityl resins have been widely used in both solid phase organic and peptide chemistry. These resins are very acid labile and can be cleaved with acetic acid. Protected peptides can be cleaved with 1:4 v/v hexafluoroisopropyl alcohol/dichloromethane with all sidechain protecting groups intact, even trityl groups on sulfhydryl function of homocysteine. These resins are particularly useful when less acid labile protecting groups are required on the substrate following cleavage, or in cases where the substrate can cyclize on the anchoring linkage causing premature cleavage. The bulky triphenylmethyl group prevents such attack through steric hindrance. In addition to being used to immobilize acids and alcohols, trityl resins can also be used to immobilize amines or thiols.
Barlos has reported that the 2-chlorotrityl resin has better stability during peptide synthesis than the trityl resin. The 2-chlorotrityl resins are available in the chloride form. The chloride form is exceedingly moisture sensitive and must be handled and stored under inert conditions. Should the resin become deactivated, treatment with thionyl chloride immediately before use restores the activity.