Kdo化学合成方法改进

doi:10.5246/jcps.2022.02.008

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (2): 97-107.DOI: 10.5246/jcps.2022.02.008

Kdo化学合成方法改进

孙遨, 李紫鹏, 刘婷, 孟祥豹, 李树春^*(), 李中军^*()

北京大学医学部药学院天然药物及仿生药物国家重点实验室; 化学生物学系, 北京 100191

收稿日期:2021-10-25 修回日期:2021-11-17 接受日期:2021-11-29 出版日期:2022-02-27 发布日期:2022-02-25
通讯作者: 李树春, 李中军
作者简介:
+ Tel.: +86-10-82801714, E-mail: scli@bjmu.edu.cn
+ Tel.: +86-10-82805939, E-mail: zjli@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81930097, 21977005).

Improvement of Kdo's efficient large-scale chemical synthesis method

Ao Sun, Zipeng Li, Ting Liu, Xiangbao Meng, Shuchun Li^*(), Zhongjun Li^*()

The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2021-10-25 Revised:2021-11-17 Accepted:2021-11-29 Online:2022-02-27 Published:2022-02-25
Contact: Shuchun Li, Zhongjun Li

摘要/Abstract

摘要：

Kdo残基作为细菌脂多糖和荚膜多糖的组成成分广泛分布于细菌中, 可被人体适应性免疫系统识别, 具有开发新型糖芯片、抗菌疫苗的巨大潜力。通过对现有方法的改进, 优化了Kdo化学合成方法, 高效合成纯度较高的Kdo单糖, 改进的方法具有可放大性。Kdo酰化过程极易形成1,5-内酯, 降低合成效率。通过改变合成顺序, 规避了Kdo 1,5-内酯的生成, 提高了Kdo糖烯的合成效率, 为衍生化提供了新策略。

关键词: Kdo, 化学合成, 1,5-内酯, 糖烯

Abstract:

Kdo residues are widely distributed in bacteria. They are components of bacterial lipopolysaccharide (LPS) and capsular polysaccharides, which can be recognized by the human adaptive immune system, and have great potential for developing new sugar chips and antibacterial vaccines. By improving the existing methods, we optimized the Kdo chemical synthesis method, which was able to efficiently synthesize Kdo monosaccharides with high purity, laying a foundation for the construction of subsequent compound libraries. Kdo acylation can easily form 1,5-lactones and reduce the efficiency of synthesis. By changing the synthesis sequence, we avoided the formation of Kdo 1,5-lactones, improved the synthesis efficiency of Kdo glycals, and provided a new strategy for derivatization.

Key words: Kdo, Chemical synthesis, 1,5-Lactone, Glycal

Supporting:

孙遨, 李紫鹏, 刘婷, 孟祥豹, 李树春, 李中军. Kdo化学合成方法改进[J]. 中国药学(英文版), 2022, 31(2): 97-107.

Ao Sun, Zipeng Li, Ting Liu, Xiangbao Meng, Shuchun Li, Zhongjun Li. Improvement of Kdo's efficient large-scale chemical synthesis method[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(2): 97-107.

图/表 5

Scheme 1. Kdo's Fischer projection and 4C1 conformation.

Scheme 2. Kdo 1,5-lactone formation.

Scheme 3. Improvement of synthesis route of intermediate phosphate.

Scheme 4. Chai's Kdo synthesis method.

Scheme 5. Improvement of Kdo glycal synthesis route.

参考文献 18

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Kdo化学合成方法改进

Improvement of Kdo's efficient large-scale chemical synthesis method

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