Stereochemical Studies on Sialic Acid Derivatives

1.以食用燕窝为原料合成了KDNNeu5Ac，以D-甘露糖和草酸为原料合成了KDN。这是因为Neu5Ac亚硝基衍生物的热重排产率很低。以(Neu4，5，7，8，9-Ac_52betaCl1Me)为原料合成了各种Neu5Ac衍生物。以氯化物为原料，在Koenigs-Knorr反应条件下合成了唾液糖基-乳糖、-胆固醇、-单糖和-二糖核苷类似物。在柯尼希法下合成了KDNBenzyl(3-deoxy-D-glycero-alpha-D-galacto-2-nonulopyranosid)甲酯)和2-(5-胆烯基-3β-氧基)-3-deoxy-D-glycero-alpha-and-beta-D-galacto-2-nonulopyranosonate钠的糖基化反应。以4，5，7，8，9-penta-0-acetyl-3-deoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl溴代苯甲酸苄酯为糖基供体。威廉森反应的糖基化反应将阿魏酸、雌二醇、伊马福隆和丝裂霉素类化合物与Neu5Ac氯化物进行糖基化反应，以较好的产率合成了α-糖苷。用类似的方法制备丝裂霉素衍生物。立体化学的确认(1)用核磁共振和圆二色谱方法确定了它们的结构和立体化学。(2)证明了α-和β-甲基神经氨酸的水解法。α-异构体在1小时内被水解，而β-异构体在5小时后稳定。同样，α-(2-&gt；6)唾液糖基乳糖在80ﾟC下1小时即可完全水解。相反，β-异构体在80^ﾟ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.