Synthesis of Carbohydrate-Functionalised Sequence-Defined Oligo(amidoamine)s by Photochemical ThiolEne Coupling in a Continuous Flow Reactor
Synthesis of Carbohydrate-Functionalised Sequence-Defined Oligo(amidoamine)s by Photochemical ThiolEne Coupling in a Continuous Flow Reactor
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DOI：
10.1002/chem.201203927
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发表时间：
2013-02-01
影响因子：
4.3
通讯作者：
Hartmann, Laura
中科院分区：
文献类型：
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作者：
Wojcik, Felix;O'Brien, Alexander G.;Hartmann, Laura
多聚/低聚(氨基胺)S(PAAS)最近被认为是一种潜在的多碳水化合物呈递的良好支架和多价配体。在这里，我们报道了两种互补的策略来制备这种序列定义的碳水化合物功能化的PAAS，它们使用光化学硫烯偶联(TEC)作为已建立的叠氮炔环加成(CLICK)反应的替代。在第一种方法中，含有多个烯烃的PAAS是在一种新的构筑块的固体载体上合成的，然后与未保护的硫代碳水化合物偶联。或者，通过使用TEC制备预官能化构建块并组装在固体载体上以提供碳水化合物功能化的PAA。这两种方法都依赖于使用连续流动光反应器进行TEC反应。由于其路径长度短，该体系是高效的，并且不需要额外的自由基引发剂。在特氟龙AF-2400管材中，在254 nm处进行反应，为碳水化合物的偶联提供了高效的TEC程序，如O-烯丙基糖苷与硫醇的反应所证明的那样。该方法允许在单个步骤中完成PAA主干上的所有反应位点的官能化，从而获得定义的均一序列。此外，在流动反应器中FEP管内在366 nm处的反应使得大规模合成了一种由荧甲氧羰基(FMOC)保护的糖基化构建块，这被证明是适合于固相合成的，并且还将允许沿低聚物骨架的不同碳水化合物的异相序列控制。这些进展使得合成序列定义的碳水化合物功能化的PAAS具有潜在的生物学应用。
Poly/oligo(amidoamine)s (PAAs) have recently been recognised for their potential as well-defined scaffolds for multiple carbohydrate presentation and as multivalent ligands. Herein, we report two complimentary strategies for the preparation of such sequence-defined carbohydrate-functionalised PAAs that use photochemical thiolene coupling (TEC) as an alternative to the established azidealkyne cycloaddition (click) reaction. In the first approach, PAAs that contained multiple olefins were synthesised on a solid support from a new building block and subsequent conjugation with unprotected thio-carbohydrates. Alternatively, a pre-functionalised building block was prepared by using TEC and assembled on a solid support to provide a carbohydrate-functionalised PAA. Both methods rely on the use of a continuous flow photoreactor for the TEC reactions. This system is highly efficient, owing to its short path length, and requires no additional radical initiator. Performing the reactions at 254nm in Teflon AF-2400 tubing provides a highly efficient TEC procedure for carbohydrate conjugation, as demonstrated in the reactions of O-allyl glycosides with thiols. This method allowed the complete functionalisation of all of the reactive sites on the PAA backbone in a single step, thereby obtaining a defined homogeneous sequence. Furthermore, reaction at 366nm in FEP tubing in the flow reactor enabled the large-scale synthesis of an fluorenylmethyloxycarbonyl (Fmoc)-protected glycosylated building block, which was shown to be suitable for solid-phase synthesis and will also allow heterogeneous sequence control of different carbohydrates along the oligomeric backbone. These developments enable the synthesis of sequence-defined carbohydrate-functionalised PAAs with potential biological applications.