School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.
J Org Chem. 2021 Jun 4;86(11):7725-7756. doi: 10.1021/acs.joc.1c00796. Epub 2021 May 24.
Protein-carbohydrate interactions are implicated in many biochemical/biological processes that are fundamental to life and to human health. Fluorinated carbohydrate analogues play an important role in the study of these interactions and find application as probes in chemical biology and as drugs/diagnostics in medicine. The availability and/or efficient synthesis of a wide variety of fluorinated carbohydrates is thus of great interest. Here, we report a detailed study on the synthesis of monosaccharides in which the hydroxy groups at their 4- and 6-positions are replaced by all possible mono- and difluorinated motifs. Minimization of protecting group use was a key aim. It was found that introducing electronegative substituents, either as protecting groups or as deoxygenation intermediates, was generally beneficial for increasing deoxyfluorination yields. A detailed structural study of this set of analogues demonstrated that dideoxygenation/fluorination at the 4,6-positions caused very little distortion both in the solid state and in aqueous solution. Unexpected trends in α/β anomeric ratios were identified. Increasing fluorine content always increased the α/β ratio, with very little difference between regio- or stereoisomers, except when 4,6-difluorinated.
蛋白质-碳水化合物相互作用涉及许多对生命和人类健康至关重要的生化/生物学过程。氟化碳水化合物类似物在这些相互作用的研究中起着重要的作用，并作为化学生物学中的探针以及医学中的药物/诊断试剂得到应用。因此，广泛的氟化碳水化合物的可用性和/或高效合成具有重要意义。在这里，我们报告了一项关于单糖合成的详细研究，其中其 4-和 6-位的羟基被所有可能的单氟化和双氟化基取代。最小化保护基的使用是一个关键目标。结果发现，引入电负性取代基，无论是作为保护基还是作为脱氧中间体，通常有利于提高脱氧氟化产率。对这组类似物的详细结构研究表明，4,6-位的双脱氧/氟化在固态和水溶液中几乎不会引起结构扭曲。确定了 α/β 端基比的意外趋势。氟含量的增加总是会增加 α/β 比，区域或立体异构体之间几乎没有差异，除了 4,6-二氟化时。
