Studies on glycan processing inhibitors

1.以N-乙酰神经氨酸（Neu 5Ac）的2-β-SNa衍生物分别与胞苷、脱氧胞苷、阿糖基、胞嘧啶通过（a）-SCH_2O-和（B）-SCH_2CONH-等间隔臂连接，得到相应的CMP-Neu 5Ac衍生物和类似物。这些化合物对Neu 5Ac合成酶和Neu 5Ac转移酶具有抑制活性，可用于分析细胞表面唾液糖缀合物的生物学功能。2-酮基-3-脱氧-辛糖酸（KDO）的2-β-SNa衍生物也已合成并分别与胞苷、脱氧胞苷和阿拉伯糖基胞嘧啶组合，如Neu 5Ac所述。2.1-脱氧野尻霉素（DNJ）经环氧化物中间体转化为一系列N-乙酰氨基己糖类似物，即N-乙酰氨基己糖。例如，2-乙酰氨基-1，2，5-三脱氧-1，5-亚氨基-D-葡萄糖醇（GlcNAcDNJ）、-D-甘露醇（ManNAcDNJ）、-D-半乳糖醇（GalNAcDNJ）及其异构体。检测了对相应的N-乙酰氨基己糖苷酶的抑制活性。GlcNAcDNJ被进一步转化为与乳糖、乳糖胺和壳二糖相关的二糖，其是广泛的糖缀合物的主要组分。将设计含有DNJ作为还原末端组分的更复杂的聚糖。

1. The 2-beta-SNa derivative of N-acetylneuraminic acid (Neu5Ac) was combined with cytidine, deoxycytidine and arabinosyl,cytosine, respectively, through the spacer-arms such as (a) -SCH_2O- and (b) -SCH_2CONH-, to give the corresponding CMP-Neu5Ac derivatives and analogs. These compounds showed the inhibition activity against Neu5Ac synthase and Neu5Ac transferase, and might be useful to analyze the biological functions of cell-surface sialo-glycoconjugates. The 2-beta-SNa derivative of 2-keto-3-deoxy-octonic acid (KDO) has, also been synthesized and combined with cytidine, deoxycytidine and arabinosyl cytosine, respectively, as described for Neu5Ac. The biological activities are now in investigation.2.1-Deoxynojirimycin (DNJ) was converted, via the epoxide intermediates, into a series of N-acetylhexosamine analogs, i. e., 2-acetamido-1,2,5-trideoxy-1,5-imino- D-glucitol (GlcNAcDNJ), -D-mannitol (ManNAcDNJ), -D-galactitol (GalNAcDNJ) and their isomers. The inhibition activity against the corresponding N-acetylhexosaminidase was examines. GlcNAcDNJ was further converted to the disaccharides related to lactose, lactosamine and chitobiose which are the prominent components of widespread glycoconjugates. More complex glycans containing DNJ as a reducing-end component will be designed.