Zhao Gaoyuan, Mukherjee Upasana, Zhou Lin, Mauro Jaclyn N, Wu Yue, Liu Peng, Ngai Ming-Yu
Department of Chemistry and Institute of Chemical Biology and Drug Discovery, the State University of New York at Stony Brook, Stony Brook, New York 11794.
Department of Chemistry and Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
CCS Chem. 2023 Jan;5(1):106-116. doi: 10.31635/ccschem.022.202202282. Epub 2022 Oct 10.
-Glycosides are important carbohydrate mimetics found in natural products, bioactive compounds, and marketed drugs. However, stereoselective preparation of this class of glycomimetics remains a significant challenge in organic synthesis. Herein, we report an excited-state palladium-catalyzed α-selective -ketonylation strategy using readily available 1-bromosugars to access a range of -glycosides. The reaction features excellent -selectivity and mild conditions that tolerate a wide range of functional groups and complex molecular architectures. The resulting α-ketonylsugars can serve as versatile precursors for their β-isomers and other -glycosides. Preliminary experimental and computational studies of the mechanism suggest a radical pathway involving the formation of palladoradical and glycosyl radical that undergoes polarity-mismatched coupling with silyl enol ether, affording the desired α-ketonylsugars. Insight into the reactivity and mechanism will inspire new reaction development and provide straightforward access to both α- and β--glycosides, greatly expanding the chemical and patent spaces of glycomimetics.
糖苷是天然产物、生物活性化合物和市售药物中重要的碳水化合物模拟物。然而，这类糖模拟物的立体选择性制备在有机合成中仍然是一项重大挑战。在此，我们报道了一种激发态钯催化的α-选择性酮基化策略，使用易于获得的1-溴代糖来合成一系列糖苷。该反应具有优异的α-选择性和温和的条件，能够耐受多种官能团和复杂的分子结构。所得的α-酮基糖可作为其β-异构体和其他糖苷的通用前体。对该反应机理的初步实验和计算研究表明，这是一条涉及钯自由基和糖基自由基形成的自由基途径，该自由基与硅烯醇醚发生极性不匹配偶联，从而得到所需的α-酮基糖。对反应活性和机理的深入了解将激发新反应的开发，并为α-和β-糖苷提供直接的合成方法，极大地扩展了糖模拟物的化学和专利空间。
