Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31-310, Lower Hutt, New Zealand.
J Org Chem. 2011 Jun 17;76(12):4941-51. doi: 10.1021/jo200588u. Epub 2011 May 24.
Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of phosphoglycolipids with significant immune-modulating properties. We present here the synthesis of dipalmitoyl phosphatidylinositol hexamannoside (PIM(6)) 1 and the first reported functional biology of a synthetic PIM(6). Key steps in the synthetic protocol included the selective glycosylation of an inositol 2,6-diol with a suitably protected mannosyl donor and construction of the glycan core utilizing a [3 + 4] thio-glycosylation strategy. The target 1 was purified by reverse phase chromatography and characterized by standard spectroscopic methods, HPLC, and chemical modification by deacylation to dPIM(6). The (1)H NMR spectrum of synthetic dPIM(6) obtained from 1 matched that of dPIM(6) obtained from nature. PIM(6) (1) exhibited dendritic cell-dependent suppression of CD8(+) T cell expansion in a human mixed lymphocyte reaction consistent with the well established immunosuppressive activity of whole mycobacteria.
从分枝杆菌中分离出的磷酸肌醇甘露糖苷（PIM）已被确定为一类具有重要免疫调节特性的磷酸糖脂。我们在此介绍了二棕榈酰磷脂酰肌醇六甘露糖苷（PIM（6））1 的合成以及首个报道的合成 PIM（6）的功能生物学。合成方案中的关键步骤包括与适当保护的甘露糖供体选择性地糖苷化肌醇 2,6-二醇，并利用[3+4]硫代糖基化策略构建糖苷核心。目标物 1 通过反相色谱法进行纯化，并通过标准光谱方法、HPLC 和通过脱酰基反应转化为 dPIM（6）进行化学修饰进行表征。从 1 获得的合成 dPIM（6）的（1）H NMR 谱与从天然产物中获得的 dPIM（6）的（1）H NMR 谱相匹配。PIM（6）（1）在人混合淋巴细胞反应中表现出树突状细胞依赖性抑制 CD8+T 细胞扩增，与整个分枝杆菌的既定免疫抑制活性一致。
