Development of Sialic Acid Related Compounds to Immunological Regulator

唾液酸作为糖蛋白、糖脂和寡糖的组成成分在许多动物细胞中起着重要作用。最重要的唾液酸N-乙酰神经氨酸结晶为不同的形式，并且两种晶体的端基异构体构型被证实为<beta>-构型。以2-氯-N-乙酰基-4，7，8，9-四-O-乙酰基-β-D-神经氨酸甲酯为起始原料，合成了粘蛋白类似物、唾液乳糖、单糖和二糖核苷类似物等唾液酸衍生<beta>物，并通过核磁共振和圆二色性光谱的测定证实了它们的立体化学结构。通过HPLC对糖苷键的水解实验也可证实其端基异构体的立体化学结构。唾液酸衍生物显示了小鼠淋巴细胞的增殖和免疫功能。特别是5-氟-2 '，3'-O-异亚丙基（KI-8110）和2 '，3'-二-O-乙酰肌苷（KI-8115）衍生物，由于抑制淋巴细胞表面的唾液酸转移酶，KI-8110抑制NL-17和NL-44细胞中唾液酸向其内源性受体的转移，并抑制肺转移。

Sialic acid as constituents of glycoproteins, glycolipids, and oligosaccharides plays an important role in many animal cells. N-Acetylneuraminic acid the most important sialic acid was crystallized to different forms, and the anomeric configuration of both crystls was confirmed as the <beta> -configuration. Syntheses of various kind of sialic acid derivatives - mucin analogs, sialyllactose, monosaccharide and disaccharide nucleoside analogs - were prepared from methyl 2-chloro-N-acetyl-4,7,8,9-tetra-O-acetyl- <beta> -D-neuraminate.Confirmation of the stereochemistry of these derivatives was performed by means of NMR and CD spectral determination. Hydrolysis experiment of the glycosidic bond by HPLC was also useful method for confirmation of anomeric stereochemistry.Sialic acid derivatives show proliferal and immunological functions of murine lymphocyte. Especially, 5-fluoro-2',3'-O-isopropylidene (KI-8110) and 2',3'-di-O-acetylinosine (KI-8115) derivatives were most effective owing to the inhibition of sialyltransferase on the lymphocyte surface.KI-8110 inhibited the transfer of sialic acid to its endogenous acceptor in NL-17 and NL-44 cells, and inhibited the metastasis to the lung.