Université de Strasbourg, CNRS, Institut Charles Sadron UPR22, 23 rue du Loess, 67034, Strasbourg Cedex 2, France.
Aix Marseille Université, CNRS, UMR 7273, Institute of Radical Chemistry, 13397, Marseille Cedex 20, France.
Macromol Rapid Commun. 2017 Dec;38(24). doi: 10.1002/marc.201700651. Epub 2017 Nov 16.
A photoregulated phosphoramidite iterative process is studied for the synthesis of non-natural, digitally encoded oligo(phosphodiester)s. The oligomers are prepared using two reactive phosphoramidite monomers containing a 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protected OH group. The stepwise synthesis is performed on an OH-functional soluble polystyrene support, which allows recycling by precipitation in a nonsolvent. Repeating cycles involving phosphoramidite coupling, oxidation of phosphite to phosphate, and NPPOC deprotection by light irradiation at λ = 365 nm are performed in order to prepare oligomers with different lengths and sequences. Synthesis is conducted on a micromolar scale and good recycling yields are obtained in all cases. The use of a soluble polymer support allows an in-depth characterization of the NPPOC photo-deprotection step by H NMR, UV spectroscopy, and size exclusion chromatography, and thus identification of optimal synthesis conditions. After cleavage from the support, the oligo(phosphodiester)s are characterized by tandem mass spectrometry, which confirms preparation of uniform sequence-coded oligomers.
我们研究了一种光调控的亚磷酰胺迭代过程，用于合成非天然的、数字编码的寡（磷酸二酯）。这些寡聚物是使用两种含有 2-(2-硝基苯)丙氧基羰基 (NPPOC) 保护的 OH 基团的反应性亚磷酰胺单体制备的。逐步合成在 OH 功能化的可溶性聚苯乙烯载体上进行，通过在非溶剂中沉淀进行回收。重复进行亚磷酰胺偶联、亚膦酸酯氧化和 NPPOC 在 λ = 365nm 光照射下脱保护的循环，以制备具有不同长度和序列的寡聚物。合成在微摩尔规模上进行，在所有情况下都获得了良好的回收产率。使用可溶性聚合物载体可以通过 1H NMR、UV 光谱和尺寸排阻色谱法深入表征 NPPOC 光脱保护步骤，从而确定最佳的合成条件。从载体上切割下来后，寡（磷酸二酯）通过串联质谱法进行表征，这证实了均匀序列编码寡聚物的制备。
