Efficient automated solid-phase synthesis of recognition-encoded melamine oligomers

Abstract

Recognition-encoded melamine oligomers (REMO) are synthetic polymers with an alternating 1,3,5-triazine-piperazine backbone and side chains equipped with either a phenol or phosphine oxide recognition unit. Here, we describe an automated method for highly efficient solid-phase synthesis (SPS) of REMO of any specified length and sequence. These SPS protocols are amongst the most robust reported to date, as demonstrated by the synthesis of a mixed-sequence 42-mer, which was obtained in excellent crude purity on a 100 mg scale. Starting from loaded Wang resin and dichlorotriazine monomer building blocks, the SPS methods were automated and optimised on a commercial peptide synthesiser. Major side products were identified using LCMS, and the undesired side reactions were suppressed by the choice of resin, solvent and coupling conditions. REMO have been shown to form high-fidelity length- and sequence-selective H-bonded duplexes, analogous to nucleic acids, and automated synthesis will facilitate exploration of related functional properties, such as molecular replication and programmable self-assembly.