Peptoid synthesis using the submonomer process is an inherently green process from the perspective of atom economy because protecting groups are not necessary, but prodigiously wasteful in the number of reagent equivalents used.  In comparison, peptide synthesis routinely employs room temperature reactions on the order of one minute in length.  To enable the utilization of the full potential of peptoids by enabling greener and faster synthesis of even longer peptoids, we investigated the lower limits of reagent concentrations and reaction times.  Our eicosamer (20mer) peptoid syntheses revealed high yields and purities at reagent concentrations as low as 0.15-0.2 M (an order of magnitude lower than standard conditions) and reaction times as short as one minute at room temperature (one to two orders of magnitude lower than standard conditions). These one minute reaction times are applicable even for historically challenging chiral alpha-branched amines such as (S)-1-phenylethylamine.  Given the remarkable purity obtained from these short reaction times and the syntheses of longer oligomers they enable, we then synthesized the first truly sequence-specific nearly perfectly monodisperse peptoid polymers (50mers-100mers with molecular weights up to and exceeding 10 kDa).  These are the longest sequence-specific peptoids ever synthesized and readily match or surpass monodispersities of peptoids synthesized using solution polymerization techniques while retaining full sequence specificity.

Faster and greener: One minute reactions for synthesis of peptoid oligomers and polymers

247th National Meeting (2014)

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