Synthesis of building blocks for an iterative approach towards oligomers of the Streptococcus pneumoniae type 1 zwitterionic capsular polysaccharide repeating unit
Synthesis of building blocks for an iterative approach towards oligomers of the Streptococcus pneumoniae type 1 zwitterionic capsular polysaccharide repeating unit
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DOI：
10.1139/cjc-2016-0006
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发表时间：
2016-11-01
影响因子：
1.1
通讯作者：
Oscarson, Stefan
中科院分区：
文献类型：
--
作者：
Ni Cheallaigh, Aisling;Oscarson, Stefan
两性离子荚膜多糖提取物，类似于8 kDa的质量，从肺炎链球菌1型（Spt 1）已显示出独特的T细胞活化特性。需要确定长度的Spt 1荚膜多糖[-> 3）-4-NH 2-a-D-QuipNAc-（1 -> 4）-a-D-GalpA-（1 -> 3）-a-D-GalpA-（1-]（n）的三糖重复单元的低聚物来进一步研究该响应。描述了一种朝向Spt 1的两性离子荚膜多糖的可迭代延伸的三糖构建块的方法。关键要素包括使用硫代糖苷供体对目标三糖进行糖基化前氧化和糖基化后氧化方法的比较、糖基化后氧化方法的优化以及三糖转化为针对迭代糖基化定制的结构单元。还描述了用于常见细菌2-乙酰氨基-4-氨基-2，4，6-三脱氧-α-D-吡喃半乳糖苷基序的立体可调的2-N-3-O-恶唑烷酮供体的构建和评价，这是其有效合成的关键中间体。
Zwitterionic capsular polysaccharide extracts, similar to 8 kDa in mass, from Streptococcus pneumoniae type 1 (Spt1) have shown unique T-cell activating properties. Oligomers of the trisaccharide repeating unit of the Spt1 capsular polysaccharide [-> 3)-4-NH2-alpha-D-QuipNAc-(1 -> 4)-alpha-D-GalpA-(1 -> 3)-alpha-D-GalpA-(1-](n) of defined length are needed to further investigate this response. An approach towards iteratively extendable trisaccharide building blocks of the zwitterionic capsular polysaccharides of Spt1 is described. Key elements include the comparison of pre-glycosylation oxidation and post-glycosylation oxidation approaches using thioglycoside donors to the target trisaccharide, the optimisation of the post-glycosylation oxidation approach, and the conversion of the trisaccharide to building blocks tailored for iterative glycosylation. The construction and evaluation of stereotunable 2-N-3-O-oxazolidinone donors for the common bacterial 2-acetamido-4-amino-2,4,6-trideoxy-alpha-D-galactopyranoside motif is also described, as is a key intermediate for their efficient synthesis.