Institut für Organische Chemie der Technischen Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
Beilstein J Org Chem. 2010 Feb 2;6:9. doi: 10.3762/bjoc.6.9.
Compounds 4 and 5, including both 4(5)-substituted imidazole or 3-substituted indole units as the entities used in nature, and 2-aminopyridine group as a heterocyclic analogue of the asparagine/glutamine primary amide side chain, were prepared and their binding properties towards carbohydrates were studied. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein-carbohydrate complexes. ¹H NMR spectroscopic titrations in competitive and non-competitive media as well as binding studies in two-phase systems, such as dissolution of solid carbohydrates in apolar media, revealed both highly effective recognition of neutral carbohydrates and interesting binding preferences of these acyclic compounds. Compared to the previously described acyclic receptors, compounds 4 and 5 showed significantly increased binding affinity towards β-galactoside. Both receptors display high β- vs. α-anomer binding preferences in the recognition of glycosides. It has been shown that both hydrogen bonding and interactions of the carbohydrate CH units with the aromatic rings of the receptors contribute to the stabilization of the receptor-carbohydrate complexes. The molecular modeling calculations, synthesis and binding properties of 4 and 5 towards selected carbohydrates are described and compared with those of the previously described receptors.
化合物 4 和 5,包括作为自然界中实体使用的 4(5)-取代咪唑或 3-取代吲哚单元,以及 2-氨基吡啶基团作为天冬酰胺/谷氨酰胺仲酰胺侧链的杂环类似物,被制备并研究了它们与碳水化合物的结合性质。这些受体的设计灵感来自于蛋白质-碳水化合物复合物晶体结构中观察到的结合模式。¹H NMR 光谱滴定在竞争性和非竞争性介质以及两相体系中的结合研究,如非极性介质中固体碳水化合物的溶解,揭示了这些无环化合物对中性碳水化合物的高效识别和有趣的结合偏好。与之前描述的无环受体相比,化合物 4 和 5 对 β-半乳糖苷表现出显著增加的结合亲和力。这两种受体在糖苷的识别中都表现出高的β-对α-异构体的结合偏好。已经表明,氢键和碳水化合物 CH 单元与受体的芳环之间的相互作用都有助于稳定受体-碳水化合物复合物。描述了 4 和 5 对选定碳水化合物的分子建模计算、合成和结合性质,并与之前描述的受体进行了比较。