Merrifield resin is one of the standard supports for the synthesis of peptides by Boc strategy. Originally, the cesium salt of a protected amino acid was anchored to the chloromethyl support via nucleophilic displacement of chlorine. Me₄N salts, sodium salts in THF with Bu₄NF catalysis, and zinc salts in EtOH have been used as well. Cleavage is normally effected by treatment with HF or TFMSA or by catalytic transfer hydrogenolysis, alcohols can be released by using diisobutylaluminium hydride or LiBH₄. For cleavage scavengers may be required. New isomeric trialkoxybenzylamine resins have been developed by coupling phthalimidomethyl-3,5-dimethoxyphenols to this resin followed by subsequent treatment with hydrazine, that allows DCC coupling with the carboxyl function of amino acids or peptides. The addition of alcohols can be performed by heating the corresponding potassium or sodium alkoxide and the resin in DMF. Reductive cleavage of the anchoring ester linkage was also accomplished. Attachment of sodium dihydrocinnamate to this resin and treatment with a solution of lithium diisopropylamide (LDA) in THF formed a resin-bound zinc enolate for aldol condensations. Reductive cleavage with diisobutylaluminium hydride afforded a 1,3-diol library. The removal of β-lactams has been achieved by using aluminium chloride. Another application of this support to nonpeptides involved anchoring the cesium salts of bromo or iodobenzoic acids followed by subsequent transformation into biaryl derivatives using Suzuki coupling conditions. The products were released from the resin via nucleophilic attack with methoxide ion to give methyl esters.
Bachem offers a large variety of Boc-amino acids linked to Merrifield resin.