Zeolites employed as basic catalyst for nucleophilic substitution reactions: An analysis of the adopted approach and hypothesized new perspectives

[Display omitted] •A cysteine sulfhydryl group is responsible of the nucleophilic attack on a wide range of substrates and the process is promoted by the basic sites of activated Zeolites A. It results in a chemoselective and in some case stereoselective reaction.•The catalysis occurs on the external surface of the zeolite, as also assessed by the FT-IR analysis.•The developed methodology allows an efficient one-pot introduction of exogenous moieties into peptides, useful for developing peptidomimetic and/or peptide-based probes. The present article reports on an excursus of substitution reactions performed on different halo-compounds and several cyclic sulfamidates that are readily accessible to nucleophilic attack. Essentially, a cysteine sulfhydryl group is employed as nucleophile and the process is promoted by the basic sites of activated Zeolites A (4 Å molecular sieves). The catalysis occurs on the external surface of the zeolite, as also assessed by the FT-IR analysis executed on molecules adsorbed on the catalyst. The moderate basicity of the zeolite lattice surface is the prerequisite for conducting chemoselective and in some case stereoselective peptide modifications. The developed methodology allows an efficient one-pot introduction of exogenous moieties into peptides, useful for developing peptidomimetic and/or peptide-based probes.