Chemical Study on Immunostimulating Natural Glycoconjugates

我们对细菌细胞表面的两亲性糖偶联物进行了合成和结构研究，以研究其特有的免疫刺激和抗肿瘤活性的化学实体。化脓性葡萄球菌的脂磷壁酸(LTA)是我们合成的第一个目标，因为最近发现这种特定的LTA具有抗肿瘤活性。根据所提出的结构，分别合成聚磷酸甘油和糖脂部分，然后将它们偶联在一起形成所需的LTA基本结构。以D-甘露醇为原料制备手性保护的甘油组分，通过一种新的有效方法合成光学纯净的甘油磷酸部分。甘油之间的磷酸二酯是通过亚磷酰胺过程形成的。对于糖脂的形成，人们开发了新的和通用的方法来选择性地保护羟基，方法是通过对-硝基和对-别戊酰氨基苯甲基。在完全解除保护后，合成的LTA及其部分结构正在进行生物学测试。通过凝胶过滤和分配层析，从BCG细胞中发现了一种新的免疫刺激糖偶联物，并证明它是一种不同于革兰氏阴性细菌的新型脂多糖。从牛拉弗内尔分枝杆菌的细胞中也分离到了类似的化合物。

Synthetic and structural studies were performed on amphiphilic glycoconjugates from bacterial cell surfaces in order to study the respective chemical entities responsible for their characteristic immunostimulating and antitumor activities.Lipoteichoic Acid (LTA) of Staphylococcus pyogenes was the first target of our synthesis because of the recently described antitumor activity of this particular LTA. According to the proposed structure, the poly (glycerol phosphate) and the glycolipid part were synthesized separately and then coupled together to form the desired basic structure of the LTA. The optically pure glycerol phosphate part was synthesized by a novel efficient procedure from chirally protected glycerol components, which were prepared from D-mannitol. The phophodiesters between glycerols were formed by the phosphoroamidite procedure. For the formation of the glycolipid, novel and versatile methods for selective protection of hydroxyl groups were exploited by means of p-nitro-and p-pivaloylaminobenzyl groups. After the complete deprotection, the synthetic LTA and its partial structures are being subjected to biological tests.A novel immunostimulating glycoconjugate recently found in BCG cells were effectively purified by gel filtration and partition chromatography and shown to be a new-type of lipopolysaccharide different from that of gram-negative bacteria. A similar compound was also isolated from cells of Mycobacterium bovis ravenel.