Stereoselective Synthesis of the O-antigen of A. baumannii ATCC 17961 Using Long-Range Levulinoyl Group Participation.
Stereoselective Synthesis of the O-antigen of A. baumannii ATCC 17961 Using Long-Range Levulinoyl Group Participation.
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DOI：
10.1002/anie.202306971
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发表时间：
2023-06
影响因子：
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通讯作者：
Liangsheng Duan;Qin Nie;Yongxin Hu;Liming Wang;Kaiyan Guo;Zhuoyi Zhou;Xu Song;Yuanhong Tu;Hui Liu;T. Hansen;Jiansong Sun;Qingju Zhang
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文献类型：
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作者：
Liangsheng Duan;Qin Nie;Yongxin Hu;Liming Wang;Kaiyan Guo;Zhuoyi Zhou;Xu Song;Yuanhong Tu;Hui Liu;T. Hansen;Jiansong Sun;Qingju Zhang
本文首次报道了A.五糖和十糖的合成。鲍曼不动杆菌ATCC 17961 O-抗原用于开发针对鲍曼不动杆菌的合成碳水化合物基疫苗。鲍曼不动杆菌感染利用我们最近引进的有机催化糖基化方法，实现了稀有糖2，3-二乙酰胺基-葡萄糖醛酸的高效合成。我们首次发现，通过氢键的长程乙酰丙酸基团参与可以导致糖基化中显著改善的β-选择性。这解决了高度支化的半乳糖受体的立体选择性问题。控制实验和DFT计算支持所提出的机制。利用乙酰丙酸基团的长程参与策略，通过高效的[2 + 1 + 2]一锅糖基化方法得到五糖供体和受体，并将其用于目标十糖的合成。
Herein, we described the first synthesis of pentasaccharide and decasaccharide of A. baumannii ATCC 17961 O-antigen for developing a synthetic carbohydrate-based vaccine against A. baumannii infection. The efficient synthesis of the rare sugar 2,3-diacetamido-glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long-range levulinoyl group participation via a hydrogen bond can result in a significantly improved β-selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long-range levulinoyl group participation strategy, pentasaccharide donor and acceptor were obtained via an efficient [2 + 1 + 2] one-pot glycosylation method, which were used for the target decasaccharide synthesis.