Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of Streptococcus dysgalactiae 2023 Polysaccharide for a PS A1 Conjugate Vaccine
Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of Streptococcus dysgalactiae 2023 Polysaccharide for a PS A1 Conjugate Vaccine
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DOI：
10.1021/acs.joc.6b00195
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发表时间：
2016-06-03
影响因子：
3.6
通讯作者：
Andreana, Peter R.
中科院分区：
文献类型：
--
作者：
Ghosh, Samir;Nishat, Sharmeen;Andreana, Peter R.
本文首次报道了从牛乳腺炎阻乳链球菌（Streptococcus dysgalactiae 2023）细胞膜中分离的一种富含鼠李糖的多糖的四糖重复单元的氨基衍生物的高效立体控制合成。该合成是利用立体选择性和会聚[2 + 2]糖基化策略完成的，该策略包括一个双糖施密特供体和一个包容性鼠李糖双糖受体。合成的氨基四糖通过生理稳定的肟键结合脆弱拟杆菌ATCC 25285/NCTC 9343的t细胞刺激免疫原PS Al，提供了第一个半合成的针对S. dysgalactiae 2023的细菌免疫原构建物。合成四糖共19步，总收率约为5.0%。
A highly efficient and stereocontrolled synthesis of an aminooxy derivative of the tetrasaccharide repeating unit of a rhamnose-rich polysaccharide isolated from the cell envelop of bovine mastitis Streptococcus dysgalactiae 2023 is reported for the first time. The synthesis was accomplished utilizing a stereoselective and convergent [2 + 2] glycosylation strategy inclusive of a disaccharide Schmidt donor and an inclusive rhamnose disaccharide acceptor. The synthetic aminooxy tetrasaccharide was conjugated to T-cell stimulating immunogen PS Al from Bacteroides fragilis ATCC 25285/NCTC 9343-via a physiologically stable oxime linkage to furnish the first semisynthetic bacterial -based immunogen construct targeting S. dysgalactiae 2023. The synthetic tetrasaccharide was assembled in 19 steps with a similar to 5.0% overall yield.