Ter Braak Floor, Houthuijs Kas J, Elferink Hidde, Kromm Alexandra, van Wieringen Teun, Berden Giel, Martens Jonathan, Oomens Jos, Boltje Thomas J
Synthetic Organic Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, the, Netherlands.
FELIX laboratory, Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 7, 6525 ED, Nijmegen, the, Netherlands.
Chemistry. 2024 Dec 5;30(68):e202402584. doi: 10.1002/chem.202402584. Epub 2024 Oct 29.
A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each glycosidic linkage has one of two possible stereo-chemical geometries, α/β or 1,2-cis/trans. An established approach to install 1,2-trans glycosidic bonds is neighboring group participation (NGP), mediated by a 2-O-acyl group. Extension of this intramolecular stabilization to nucleophilic groups located at more remote positions has also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy to characterize the molecular ions of monoacetylated sugar donors and showed how the strength of the stabilizing effect depends on the position of the participating ester group on the glycosyl donor ring as well as on its relative stereochemistry. In this work, we investigated glycosyl donors carrying two acyl groups. Using isotope labelling and isomer population analysis we were able to resolving spectra of isomeric mixtures and establish the relative contribution of individual species. We conclude that 3,4-diacetyl mannosyl donors exclusively form a dioxanium ion as a result of C-3 acyl stabilization. In contrast, the glucosyl and galactosyl cations form mixtures of C-3 and C-4 acyl participation products. Hence, the combination of isotope labeling and population analysis allows for the study of increasingly complex glycosyl cations.
寡糖合成中的一个关键挑战是糖苷键的立体选择性安装。每个糖苷键具有两种可能的立体化学几何结构之一，即α/β或1,2-顺式/反式。一种已确立的安装1,2-反式糖苷键的方法是由2-O-酰基介导的邻基参与（NGP）。也有人提出将这种分子内稳定作用扩展到位于更远位置的亲核基团，但目前仍了解甚少。此前，我们利用红外离子光谱对单乙酰化糖供体的分子离子进行了表征，并展示了稳定作用的强度如何取决于参与酯基在糖基供体环上的位置及其相对立体化学。在这项工作中，我们研究了带有两个酰基的糖基供体。通过同位素标记和异构体丰度分析，我们能够解析异构体混合物的光谱，并确定各个物种的相对贡献。我们得出结论，由于C-3酰基的稳定作用，3,4-二乙酰甘露糖基供体仅形成二氧杂环离子。相比之下，葡萄糖基和半乳糖基阳离子形成C-3和C-4酰基参与产物的混合物。因此，同位素标记和丰度分析的结合使得对日益复杂的糖基阳离子的研究成为可能。
