CHEMICAL SYNTHESIS AND STRUCTURE OF BACTERIAL POLYSACCHARIDES

这项工作旨在开发一种固相 一种与壳寡糖胶囊有关的低聚糖的合成方法 脑膜炎奈瑟菌A组的长期目标是提供一种工具 为了研究多糖的几个结构方面和 寡糖-蛋白质偶联抗原性。设计出了一个方案 其允许合成限定长度的低聚糖。自.以来 该多糖是(1-6)N-乙酰甘露糖胺的重复 采用了磷酸二酯、固相亚磷酰胺化学。 在上一次报告所述期间，一种完全受保护的六糖 完成，在卵裂过程中遇到了几个问题 固相硫化与脱除苄基保护剂 这些问题已经解决了。三苯基膦非常 有效地切割所有二硫键连接位点。使用的碘 在寡核苷酸合成中将亚磷酸盐氧化成磷酸不是 在当前的寡糖方案中有效，因为它导致切割 从固相中分离出低聚糖。叔丁基过氧化氢和 氢是温和的，被发现是首选试剂。移除 苯基保护基团的合成比较困难。新鲜的钯黑色 以环己烯为供氢体的乙醇反应效果良好。因此，现在在 原则上，整个计划可以完成，以产生解除保护 所需结构的低聚糖。我们想执行这项任务 一种用于研究寡糖的低聚糖生产方案 与A组脑膜炎双球菌疫苗抗体的相互作用。

This work has been directed towards the development of a solid phase method for the synthesis of an oligosaccharide related to the capsule of Neisseria meningitidis group A. The long term aim is to provide a tool for the study several structural aspects of polysaccharide and oligosaccharide-protein conjugate antigenicity. A scheme was devised which allows the synthesis of oligosaccharides of defined length. Since the polysaccharide is a repeat of a(1-6)N-acetylmannosamine phosphodiesters, solid phase phosphoramidite chemistry was adapted. During the previous reporting period a fully protected hexasaccharide was completed and several problems were encountered in the cleavage of the disulfied at the solid phase and removal of the benzyl protecting groups.These problems have been solved. Triphenylphosphine very efficiently cleaves all disulfide linkage sites. Iodine which is used in oligonucleotide synthesis to oxidize phosphite to phosphate was not effective in the current oligosaccharde scheme as it resulted in cleavage of the oligosaccharide from the solid phase. Tert-butyl peroxide and hydrogen are mild and were found to be the preferred reagents. Removal of the benzyl protecting group was difficult. Fresh palladium black in ethanol using cyclohexene as hydrogen donor worked well. Thus, now in principle the entire scheme could be completed to yield deprotected oligosaccharides of desired structure. We would like to execute this scheme to produce oligosaccharides for studying oligosaccharide interactions with antibodies to meningococcal group A vaccines.