Nα-Boc-Nδ-xanthyl-L-glutamine Merrifield resin

Noble metal catalysts currently dominate the landscape of chemical synthesis, but cheaper and less toxic derivatives are recently emerging as more sustainable solutions. Iron is among the possible alternative metals due to its biocompatibility and exceptional versatility. Nowadays, iron catalysts work essentially in homogeneous conditions, while heterogeneous catalysts would be better performing and more desirable systems for a broad industrial application. In this review, approaches for heterogenization of iron catalysts reported in the literature within the last two decades are summarized, and utility and critical points are discussed. The immobilization on silica of bis(arylimine)pyridyl iron complexes, good catalysts in the polymerization of olefins, is the first useful heterogeneous strategy described. Microporous molecular sieves also proved to be good iron catalyst carriers, able to provide confined geometries where olefin polymerization can occur. Same immobilizing supports (e.g., MCM-41 and MCM-48) are suitable for anchoring iron-based catalysts for styrene, cyclohexene and cyclohexane oxidation. Another excellent example is the anchoring to a Merrifield resin of an FeII-anthranilic acid complex, active in the catalytic reaction of urea with alcohols and amines for the synthesis of carbamates and N-substituted ureas, respectively. A SILP (Supported Ionic Liquid Phase) catalytic system has been successfully employed for the heterogenization of a chemoselective iron catalyst active in aldehyde hydrogenation. Finally, FeIII ions supported on polyvinylpyridine grafted chitosan made a useful heterogeneous catalytic system for C-H bond activation.

The stability of Merrifield linker in Fmoc deprotection process was quantitatively investigated by establishing working curve of two major decomposition components from two resin bound dipeptide models. By sampling reaction solution and analyzing with RP-HPLC, decomposition rate was determined. The results indicated that either α-amino acid or β-amino acid anchored Merrifield linker was endurable for Fmoc strategy peptide synthesis in common de-Fmoc conditions such as 20% piperidine/DMF and 2% DBU/2% piperidine/DMF under room temperature treatments. However, Fmoc-deprotection with microwave assistance of α-amino acid anchored peptide resin with 20% piperidine/DMF more than 20 times or β-amino acid anchored peptide resin with 2% DBU/2% piperidine/DMF more than 30 times is not recommended. Feasibility of the proposed compatibility was verified by design and synthesis of a thymic humoral factor derived peptide via Fmoc strategy on Merrifield resin. Thus by choosing moderate de-Fmoc protocol, Merrifield resin is feasible for Fmoc strategy oligopeptide synthesis.

The design and solid-phase synthesis of 1,3-thiazole-based peptidomimetic molecules is described. The solid-phase synthesis was based on the utilization of a traceless linker strategy. The synthesis starts from the conversion of chloromethyl polystyrene resin to the resin with a sulfur linker unit. The key intermediate 4-amino-thiazole-5-carboxylic acid resin is prepared in three steps from Merrifield resin. The amide coupling proceeded at the C4 and C5 positions via an Fmoc solid-phase peptide synthesis strategy. After cleavage, the final compounds were obtained in moderate yields (average 9%, 11-step overall yields) with high purities (≥87%). Geometric measurements of Cα distances and dihedral angles along with an rmsd of 0.5434 for attachment with Cα of the β-turn template suggest type IV β-turn structural motifs. Additionally, the physicochemical properties of the molecules have been evaluated.