Stereocontrolled Synthesis of α‐3‐Deoxy‐ᴅ‐manno‐oct‐2‐ulosonic Acid (α‐Kdo) Glycosides Using C3‐p‐Tolylthio‐Substituted Kdo Donors: Access to Highly Branched Kdo Oligosaccharides
Stereocontrolled Synthesis of α‐3‐Deoxy‐ᴅ‐manno‐oct‐2‐ulosonic Acid (α‐Kdo) Glycosides Using C3‐p‐Tolylthio‐Substituted Kdo Donors: Access to Highly Branched Kdo Oligosaccharides
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DOI：
10.1002/ange.202313985
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Zhongjun Li
中科院分区：
文献类型：
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作者：
Ao Sun;Zipeng Li;Yuchao Wang;Shuai Meng;Xiao Zhang;Xiangbao Meng;Shuchun Li;Zhongtang Li;Zhongjun Li
3‐Deoxy‐ᴅ‐manno‐oct‐2‐ulosonic acid (Kdo) is an eight‐carbon monosaccharide found widely in bacterial lipopolysaccharides (LPS) and capsule polysaccharides (CPS). We developed an indirect methodology for the stereoselective synthesis of α‐Kdo glycosides with a C3‐p‐tolylthio‐substituted Kdo phosphite donor. The presence of the p‐tolylthio group enhanced the reactivity, suppressed the formation of elimination by‐products (2,3‐enes), and provided complete α‐stereocontrol. A variety of Kdo α‐glycosides were synthesized by our method in excellent yields (up to 98%). After glycosylation, p‐tolylthio group can be efficiently removed by the free radical reduction. Subsequently, the orthogonality of phosphite donor and thioglycoside donor was demonstrated by the one‐pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route for the challenging 4,5‐branched Kdo trisaccharide in LPS from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8‐branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by the density functional theory (DFT) calculation.
