Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Chemistry. 2013 Feb 25;19(9):3090-8. doi: 10.1002/chem.201203927. Epub 2013 Jan 16.
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 thiol-ene coupling (TEC) as an alternative to the established azide-alkyne 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 254 nm 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 366 nm 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.
聚（寡聚）酰胺-胺（PAA）因其作为多种碳水化合物展示和多价配体的良好定义支架的潜力而受到关注。在此，我们报告了两种用于制备这种序列定义的碳水化合物功能化 PAA 的互补策略，该方法使用光化学硫醇-烯（TEC）作为替代已建立的叠氮-炔环加成（“点击”）反应。在第一种方法中，从新的构建块在固体载体上合成含有多个烯烃的 PAA，然后与未保护的硫代碳水化合物进行缀合。或者，通过 TEC 制备预功能化的构建块，并在固体载体上组装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光反应器进行 TEC 反应。由于其短路径长度，该系统非常高效，并且不需要额外的自由基引发剂。在 Teflon AF-2400 管中于 254nm 下进行反应，为碳水化合物缀合提供了高效的 TEC 程序，如 O-烯丙基糖苷与硫醇的反应所示。该方法允许在单个步骤中完全官能化 PAA 主链上的所有反应性位点，从而获得定义明确的均聚物。此外，在 FEP 管中的 366nm 下在流动反应器中进行反应能够大规模合成芴甲氧羰基（Fmoc）保护的糖基化构建块，该构建块适合固相合成，并且还允许沿低聚物主链对不同碳水化合物进行异质序列控制。这些发展使具有潜在生物学应用的序列定义的碳水化合物功能化 PAA 的合成成为可能。
