Universal Soluble Polymer Supports with Precisely Controlled Loading Capacity for Sequence-Defined Oligomer Synthesis

Soluble supports, with optimal molecular structures for iterative oligomer synthesis, were prepared by atom transfer radical copolymerization of styrene with Fmoc-amino ethyl methacrylate. Size exclusion chromatography and nuclear magnetic resonance indicated formation of copolymers with controlled chain lengths, chain ends, dispersity, and comonomer compositions. These polymers were afterward subjected to two subsequent modifications steps: (a) the debromination of their omega-chain ends via a tributyltin hydride treatment and (b) the removal of the Fmoc-protecting groups in acidic conditions, thus leading to bromine-free copolymers with a precise primary amine loading capacity. These universal amine-containing precursors were then derived into a variety of functional supports. A glycine-loaded Wang-type soluble polystyrene support was prepared in two steps and tested for peptide synthesis as well as for the preparation of digital oligo(alkoxyamine amide)s. In both cases, it was possible to obtain uniform sequence-defined oligomers as evidenced by electrospray ionization tandem mass spectrometry. However, each type of oligomer required specific experimental conditions and therefore soluble supports with an adapted loading capacity for optimal synthesis. Furthermore, the amine-containing universal precursors were also transformed into soluble supports for iterative phosphoramidite chemistry. A support was specifically conceived for the iterative synthesis of abiotic digital oligo(phosphodiester)s and another one was designed for oligonucleotide synthesis. (c) 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 403-410