Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Chemistry. 2010 Mar 15;16(11):3476-88. doi: 10.1002/chem.200902460.
Zwitterionic polysaccharides (ZPSs) from Bacteroides fragilis and Streptococcus pneumoniae display unique T-cell activities. The first synthesis of a hexasaccharide representing two repeating units of the zwitterionic capsular polysaccharide from S. pneumoniae type 1 (Sp1) is reported. Key elements of the approach are stereoselective construction of 1,4-cis-alpha-galactose linkages based on a reactive trichloroacetimidate donor that incorporates a 6-O-acetyl group, which may contribute to the high alpha selectivity in glycosylation. After assembly of the fully protected hexasaccharide from five monosaccharide synthons 2-4, 24 and 25, selective deprotection of the primary hydroxyl groups of the four galactose residues followed by oxidation to the corresponding uronic acids provides hexasaccharide 19. The trisaccharide counterpart 1 was synthesized in similar fashion from three synthons, 2-4. This approach employed both conventional and dehydrative glycosylation methodologies and avoids the use of poorly reactive uronic acid derived glycosyl donors and acceptors.
脆弱拟杆菌和肺炎链球菌的两性离子多糖（ZPS）显示出独特的 T 细胞活性。本文首次报道了肺炎链球菌 1 型（Sp1）两性离子荚膜多糖两个重复单元的六糖的合成。该方法的关键要素是基于含有 6-O-乙酰基的反应性三氯乙酰亚胺供体构建 1,4-顺式-α-半乳糖键，这可能有助于糖苷化的高 α 选择性。通过从 5 个单糖合成子 2-4、24 和 25 组装完全保护的六糖后，对四个半乳糖残基的伯羟基进行选择性脱保护，然后氧化为相应的糖醛酸，得到六糖 19。类似地，从三个合成子 2-4 合成了三糖类似物 1。该方法同时采用了常规和脱水糖基化方法，避免了使用反应性差的糖醛酸衍生的糖基供体和受体。
