posted on 2016-07-25, 00:00authored byGianni Cavallo, Abdelaziz Al Ouahabi, Laurence Oswald, Laurence Charles, Jean-François Lutz
A new orthogonal
solid-phase iterative strategy is proposed for
the synthesis of sequence-coded polymers. This approach relies on
the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical–radical
coupling. These repeated steps can be performed using two different
types of building blocks, i.e. a phosphoramidite monomer that also
contains an alkyl bromide and a hydroxy-functionalized nitroxide.
The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated
by copper bromide in step (ii) to afford a carbon-centered
radical that is spin-trapped in situ by the nitroxide.
The iterative repetition of these steps allow synthesis of uniform
polymers, as evidenced by high-resolution electrospray mass spectrometry.
Moreover, binary information could be easily implemented in the polymers
using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing
polymers are very easy to sequence by tandem mass spectrometry due
to the presence of easily cleavable alkoxyamine bonds formed in step
(ii).