Journal of the American Chemical Society 2015-04-29

Synthesis of non-natural sequence-encoded polymers using phosphoramidite chemistry.

Abdelaziz Al Ouahabi, Laurence Charles, Jean-François Lutz

Index: J. Am. Chem. Soc. 137 , 5629-35, (2015)

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Abstract

Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1') and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H and (13)C NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.