铜绿假单胞菌O-抗原双脱氧乙酰氨基二糖的合成

Synthesis of a Dideoxyacetylaminodisaccharide from Pseudomonas aeruginosa O-Antigen

关键词:  化学合成  双脱氧乙酰氨基二糖  1,2-顺式-糖苷键  正交保护

Key words:  chemical synthesis  dideoxyacetylaminodisaccharide  1,2-cis-glycosidic linkage  orthogonal protection

摘要:

目的 利用化学方法立体选择性合成一种铜绿假单胞菌O-抗原双脱氧乙酰氨基二糖。方法 以苯硒基D-葡萄糖苷为起始原料,通过端基连接臂引入、C6位羟基脱氧及C2位叠氮基的还原胺化等关键步骤,高效构建奎诺糖胺受体砌块。随后,将其与D-岩藻糖胺糖基供体进行糖苷化反应,立体选择性地合成目标α-1,3-连接的二糖。结果 成功合成了目标二糖分子,所有中间体及终产物的结构均经核磁共振、高分辨质谱及旋光分析确证,产物纯度高。结论 双脱氧乙酰氨基二糖合成路线简洁高效,目标分子产物纯度高,可为该抗原的后续免疫学与生物活性研究提供物质基础。

Abstract:

OBJECTIVE To achieve the stereoselective chemical synthesis of a dideoxyacetylaminodisaccharide derived from the O-antigen of Pseudomonas aeruginosa. METHODS Starting from phenylseleno-D-glucoside, a quinovosamine acceptor building block was efficiently constructed through key steps including the introduction of an anomeric linker, deoxygenation at the C6-hydroxyl, and reductive amination of the C2-azido group. This acceptor was then coupled with a D-fucosamine glycosyl donor via glycosylation to stereoselectively furnish the target α-1,3-linked disaccharide. RESULTS The target disaccharide was successfully synthesized. The structures of all intermediates and the final product were unambiguously confirmed by nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HRMS), and optical rotation analysis. The product was obtained with high purity. CONCLUSION A concise and efficient synthetic route was established to access the dideoxyacetylaminodisaccharide in high purity. This work provides a reliable material foundation for further immunological evaluation and bioactivity studies based on this antigenic structure.