Pasari Sandip, Manmode Sujit, Walke Gulab, Hotha Srinivas
Department of Chemistry, Indian Institute of Science Education and Research, Pune, 411 008, MH, India.
Chemistry. 2018 Jan 24;24(5):1128-1139. doi: 10.1002/chem.201704009. Epub 2017 Dec 19.
Oligosaccharides are involved in a myriad of biological phenomena. Many glycobiological experiments can be undertaken if homogenous and well-defined oligosaccharides are accessible. Mycobacterial cell walls contain arabinogalactan as one of the major constituents that is challenging for chemical synthesis. Therefore, the major aim of this investigation is to synthesise a major oligosaccharide portion of the arabinogalactan. The pentacosafuranoside (25mer) synthesis involved installation of several arabinofuranosidic linkages through neighbouring group participation for 1,2-trans linkages and oxidation-reduction strategy for the 1,2-cis Araf. A strategically placed n-pentenyl moiety at the reducing end enables ligation of biomolecular probes through celebrated cross metathesis or thiol-ene click reactions. Several linear and branched oligosaccharides were synthesised ranging from trisaccharide to pentadecasaccharide during this endeavour. Synthesis of pentacosasaccharide was accomplished in 77 steps with 0.0012 % overall yield. These oligosaccharides are envisioned to be excellent probes for understanding disease biology thereby facilitating discovery of novel antitubercular agents, vaccines and/or diagnostics.
寡糖参与了无数的生物现象。如果能够获得均质且结构明确的寡糖，就可以进行许多糖生物学实验。分枝杆菌细胞壁含有阿拉伯半乳聚糖，这是化学合成极具挑战性的主要成分之一。因此，本研究的主要目的是合成阿拉伯半乳聚糖的主要寡糖部分。二十五碳呋喃糖苷（25聚体）的合成涉及通过邻基参与安装几个阿拉伯呋喃糖苷键以形成1,2-反式连接，并采用氧化还原策略来合成1,2-顺式阿拉伯糖。在还原端策略性地引入正戊烯基部分，可通过著名的交叉复分解反应或硫醇-烯点击反应连接生物分子探针。在此过程中，合成了从三糖到十五糖的几种线性和分支寡糖。二十五碳糖的合成以77步完成，总产率为0.0012%。这些寡糖有望成为理解疾病生物学的优秀探针，从而有助于发现新型抗结核药物、疫苗和/或诊断方法。
