Departamento de Química and Centro de Investigación en Síntesis Química, Universidad de La Rioja , 26006 Logroño, Spain.
J Org Chem. 2013 Nov 1;78(21):10968-77. doi: 10.1021/jo4019396. Epub 2013 Oct 14.
A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-d-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their (4)C1 chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.
我们采用完全立体控制的丝氨酸等价 C-亲核试剂与三-O-苄基-2-硝基-D-半乳糖醛的 C-Michael 加成反应作为关键步骤，合成了几种吡喃并[3,2-b]吡咯结构。这些支架可以被视为构象受限的 Tn 抗原模拟物，正如我们通过生物测定所证明的那样。通过分子建模和 NMR 光谱学表明，吡喃糖环保留其 (4)C1 椅式构象。通过使用大豆和野豌豆凝集素作为模型凝集素的竞争定制酶联凝集素测定法，建立了预期的生物活性。所描述的合成路线简单，以及计算和实验技术的战略结合，揭示了构象特征和生物活性，证明了所制备的糖模拟物是进一步开发该支架以提供用于凝集素阻断和疫苗接种的聚糖的有前途的候选物。
