Zhang Lin, Zheng Zhichao, Zhang Yumeng, Wu Xiaopei, Tu Yuanhong, Liu Can, Wang Zhen, Wang Liming, Yang You, Zhang Qingju
National Research Centre for Carbohydrate Synthesis, College of Chemistry and Materials, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, China.
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
JACS Au. 2025 Apr 16;5(4):1903-1913. doi: 10.1021/jacsau.5c00113. eCollection 2025 Apr 28.
is a zoonotic pathogen, which can cause brain abscess, pneumonia, bacteremia, and urinary tract infection. Vaccines are economical and effective means for combating infectious diseases. Herein, we present the first total synthesis of the highly functionalized mono- and oligosaccharides of O-antigen for vaccine development. The rare 2,3-diacetamidopyranoses were generated from 3--acetyl-2-nitroglycals via an organocatalyzed one-pot relay glycosylation method. The postglycosylation oxidation strategy was used to overcome the poor reactivity of 2,3-diacetamido-aldouronic acid building blocks in glycosylation reactions. Direct amidation of alduronic acid with NH in the late stage reduced the protecting group operation and increased the synthetic efficiency. Di--butylsilylidene-directed α-galactosylation method was used to construct challenging 1,2--glycosidic bond. Six oligosaccharides of O-antigen were obtained and further conjugated to human serum albumin for antigenicity evaluation (the sera antibodies were obtained from vaccinated mouse via inactivated ). The terminal tetrasaccharide of O-antigen has been identified as a potential glycol-epitope and might be useful for vaccine development against .
是一种人畜共患病原体，可导致脑脓肿、肺炎、菌血症和尿路感染。疫苗是对抗传染病的经济有效手段。在此，我们展示了用于疫苗开发的O抗原高官能化单糖和寡糖的首次全合成。通过有机催化的一锅接力糖基化方法从3-乙酰基-2-硝基糖产生了罕见的2,3-二乙酰氨基吡喃糖。糖基化后氧化策略用于克服2,3-二乙酰氨基醛糖酸构建块在糖基化反应中较差的反应性。在后期用NH对醛糖酸进行直接酰胺化减少了保护基操作并提高了合成效率。二叔丁基硅亚基导向的α-半乳糖基化方法用于构建具有挑战性的1,2-糖苷键。获得了六种O抗原寡糖，并进一步与人血清白蛋白偶联以进行抗原性评估（血清抗体通过灭活从接种疫苗的小鼠获得）。O抗原的末端四糖已被鉴定为潜在的糖表位，可能对开发针对的疫苗有用。
