Tuberculosis, aggravated by drug-resistant strains and HIV co-infection of the causative agent Mycobacterium tuberculosis, is a global problem that affects millions of people. With essential immunoregulatory roles, phosphatidylinositol mannosides are among the cell-envelope components critical to the pathogenesis and survival of M. tuberculosis inside its host. Here we report the first synthesis of the highly complex tetraacylated phosphatidylinositol hexamannoside (Ac2PIM6), having stearic and tuberculostearic acids as lipid components. Our effort makes use of stereoelectronic and steric effects to control the regioselective and stereoselective outcomes and minimize the synthetic steps, particularly in the key desymmetrization and functionalization of myo-inositol. A short synthesis of tuberculostearic acid in six steps from the Roche ester is also described. Mice exposed to the synthesized Ac2PIM6 exhibit increased production of interleukin-4 and interferon-γ, and the corresponding adjuvant effect is shown by the induction of ovalbumin- and tetanus toxoid-specific antibodies.

中文翻译：

---

四酰基化磷脂酰肌醇六甘露糖苷的全合成及其免疫调节活性的评估。

耐药菌株和艾滋病毒结核分枝杆菌的艾滋病毒共同感染加剧了结核病，这是一个影响数百万人的全球性问题。磷脂酰肌醇甘露糖苷具有重要的免疫调节作用，是对其宿主内结核分枝杆菌的发病机理和存活至关重要的细胞包膜成分。在这里，我们报道了具有硬脂酸和结核硬脂酸作为脂质成分的高度复杂的四酰基化磷脂酰肌醇六甘露糖苷（Ac2PIM6）的首次合成。我们的工作利用立体电子和空间效应来控制区域选择性和立体选择性结果，并最大程度地减少合成步骤，尤其是在肌醇的关键去对称化和功能化方面。还描述了由罗氏酯在六个步骤中简短合成结核硬脂酸的方法。暴露于合成的Ac2PIM6的小鼠表现出白细胞介素4和干扰素-γ的产生增加，并且通过诱导卵清蛋白和破伤风类毒素特异性抗体显示出相应的佐剂作用。