title: Optimal ATRP-Made Soluble Polymer Supports for Phosphoramidite Chemistry.
abstract: Soluble polystyrene supports with optimal molecular structures for iterative phosphoramidite chemistry were prepared by atom-transfer radical polymerization (ATRP) and subsequent chain-end modification steps. The controlled radical polymerization of styrene was first performed in the presence of an 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino-functional ATRP initiator. Soluble supports of different molecular weight were prepared. Size-exclusion chromatography and NMR analysis indicated formation of well-defined polymers with controlled chain lengths and narrow dispersity. After synthesis, the bromo ω end group of the ATRP polymer was removed by dehalogenation in the presence of tributyltin hydride, and the Fmoc protecting group of the α moiety was subsequently cleaved with piperidine. The resulting α-primary amine was afterwards treated with a linker containing a carboxyl group, a cleavable ester site, and a dimethoxytrityl-protected hydroxyl group to afford ideal soluble supports for phosphoramidite chemistry. NMR analysis indicated that these chain-end modifications were quantitative. The supports were tested for the synthesis of a non-natural sequence-defined oligophosphates. High-resolution ESI-MS analysis of the cleaved oligomers indicated formation of uniform species, and thus confirmed the efficiency of the ATRP-made soluble polymer supports. In addition, the synthesis of a thymidine-loaded soluble support was achieved.
authors.affiliation: Precision Macromolecular Chemistry, Institut Charles Sadron, UPR-22 CNRS, 23 rue du Loess, 67034, Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Oswald
authors.affiliation: Precision Macromolecular Chemistry, Institut Charles Sadron, UPR-22 CNRS, 23 rue du Loess, 67034, Strasbourg, France.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Al Ouahabi
authors.affiliation: Institute of Radical Chemistry, UMR 7273, Aix-Marseille Université, 23 avenue Escadrille Normandie-Niemen, 13397, Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Charles
authors.affiliation: Precision Macromolecular Chemistry, Institut Charles Sadron, UPR-22 CNRS, 23 rue du Loess, 67034, Strasbourg, France. jflutz@unistra.fr.
authors.forename: Jean-François
authors.identifier: http://orcid.org/0000-0002-3893-2458
authors.initials: JF
authors.lastname: Lutz
keywords: information-containing oligomers; iterative synthesis; polymerization; polymers; soluble supports