Stereochemical Studies on Sialic Acid Derivatives

1. 以食用燕窝为原料合成KDNNeu5Ac，以d -甘露糖和草酸为原料合成KDN。因为Neu5Ac亚硝基衍生物热重排到KDN的产率很低。从（neu4,5,7,8,9 - ac_52betacl1me）中合成了各种Neu5Ac衍生物。以氯为原料，在Koenigs-Knorr反应条件下合成了唾液酰乳糖、-胆固醇、-单糖和-双糖核苷类似物。在Koenigs-Knorrection下合成了kdn苄基（3-脱氧-d -甘油- α -d -半乳糖-2-nonulopyranosid）酸酯和2-（5-胆固醇-3- β -氧）-3-脱氧-d -甘油- α和β -d -半乳糖-2-nonulopyranosid)酸钠。以苄基（4,5,7,8,9 -五-0-乙酰-3-脱氧-d -甘油- β -d -半乳糖-2-壬磺吡喃基溴化酯）酸酯为糖基供体。用Williamson反应进行糖基化，用Neu5Ac氯化物对阿魏酸、雌二醇、红霉素和丝裂霉素衍生物进行Williamson反应，产率高。用同样的方法制备丝裂霉素衍生物。(1)核磁共振和光盘光谱法通过核磁共振和光盘光谱分析确定了它们的结构和立体化学性质。(2)水解法证实了α -和β -甲基神经胺酸酯的水解。α -异头物在1小时内水解，β -异头物在5小时后稳定。同样，α - (2- bbb6)唾液基乳糖在80°C的温度下在1小时内完全水解。相反，β -异头物在80^ C下稳定5小时。

1. Synthesis of KDNNeu5Ac was obtained from edible bird's nest, and KDN was synthesized from D-mannose and oxalacetic acid. Because the yield of thermal rearrangement of Neu5Ac nitroso derivative to KDN was very low.2. Glycosilation of Neu5AcSyntheses of various kind of Neu5Ac derivatives were carried out from (Neu4, 5, 7, 8, 9-Ac_52betaCl1Me). From the chloride, sialosyl-lactose, -cholesterol, -monosaccharide, and -disaccharide nucleoside analogs were synthesized under the Koenigs-Knorr reaction conditions.3. Glycosylation of KDNBenzyl (methyl 3-deoxy-D-glycero-alpha-D-galacto-2-nonulopyranosid) onate and sodium 2- (5-cholestenyl-3beta-oxy) -3-deoxy-D-glycero-alpha-and-beta-D-galacto-2-nonulopyranosonate were synthesized under the Koenigs-Knorrection. Benzyl (4, 5, 7, 8, 9-penta-0-acetyl-3-deoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl bromid) onate was used as a glycosyl donor.4. Glycosylation with Williamson ReactionWilliamson reaction was applied to ferrulic acid, estradiol, umberiferon, and mitomycin derivatives with Neu5Ac chloride to yield alpha-glycosides in good yields. Mitomycin derivatives were prepared, by a similar method.5. Confirmation of stereochemistry(1) NMR and CD spectral method Their structure and stereochemistry were determined by means of NMR and CD spectral analyses.(2) Hydrolysis method Hydrolysis of alpha-and beta-methyl neuraminate were proved. alpha-Anomer was hydrolyzed in 1 hr, while, beta-anomer was stable after 5 hr. Similarly, alpha- (2->6) sialosyllactose was hydrolyzed completely at 80ﾟC in 1 hour. In contrast, the beta-anomer was stable at 80^ﾟC for 5 hr.