CHEMICAL SYNTHESIS AND STRUCTURE OF BACTERIAL POLYSACCHARIDES AND CONJUGATES

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 固相硫化和脱除苄基保护基团。 这些问题都得到了解决。三苯基膦非常有效 裂解所有二硫键连接位点。碘，用于 将亚磷酸盐氧化成磷酸盐的寡核苷酸合成没有 在当前的寡糖方案中有效，因为它导致 将低聚糖从固相中解离。叔丁基 过氧化氢和氢气是温和的，被发现是首选 试剂。脱除苯基保护基团比较困难。新鲜的 以环己烯为供氢体的钯黑在乙醇中的工作 井。因此，现在原则上整个计划可以完成到 得到所需结构的去保护低聚糖。我们想要 执行这一计划生产研究用低聚糖 低聚糖与A群脑膜炎双球菌抗体的相互作用 疫苗。

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 oligosaccharide 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.