Transition-Metal-Free Synthesis of C‑Glycosylated Phenanthridines via K2S2O8‑Mediated Oxidative Radical Decarboxylation of Uronic Acids

We have developed an efficient protocol for the synthesis of C-glycosylated phenanthridines. Tetrafuranos-4-yl and pentapyranos-5-yl radicals, generated from K2S2O8-mediated oxidative decarboxylation of furan- and pyranuronic acids, undergo attack to 2-isocyanodiphenyls and ensuing homolytic aromatic substitution to provide diverse C-glycosylated phenanthridines in satisfactory yields without resort to transition metals. This reaction tolerates various functional groups, and enables ready synthesis of complex oligosaccharide-based phenanthridines. The C-glycosylated phenanthridine derived from β-cyclodextrin has been prepared, which might be potential in medicinal and biological chemistry due to its flexible conformation.本研究开发了一种高效的C-糖苷化菲啶（C-glycosylated phenanthridines）合成策略。由过硫酸钾（K₂S₂O₈）介导的呋喃糖醛酸与吡喃糖醛酸氧化脱羧反应生成的四呋喃糖-4-基自由基与五吡喃糖-5-基自由基，可进攻2-异氰基联苯（2-isocyanodiphenyls），并经后续均裂芳香取代反应，以优异收率得到多种C-糖苷化菲啶，且无需使用过渡金属催化剂。该反应具有良好的官能团耐受性，可便捷合成基于复杂寡糖的菲啶类化合物。研究人员已制备得到源自β-环糊精（β-cyclodextrin）的C-糖苷化菲啶，由于其构象灵活，该化合物在药物化学与生物化学领域具备潜在应用价值。