水溶性6-O-琥珀酰-N-半乳糖化壳聚糖衍生物的制备与表征

Synthesis and Characterization of Water-soluble 6-O-Succinyl-N-galactosylated Chitosan Derivatives

目的:合成和表征水溶性6-O-琥珀酰-N-半乳糖化壳聚糖衍生物。方法:以壳聚糖为原料,首先在其2-NH2上进行邻苯二甲酰化将其保护起来,在-O-进行琥珀酰化,用肼解法脱去-N-保护基,制得了水溶性的6-O-琥珀酰化壳聚糖。然后6-O-琥珀酰化壳聚糖通过与乳糖酸或乳糖与KBH4的均相反应,在其2-NH2上引入了半乳糖基,制得O-琥珀酰-N-半乳糖化壳聚糖衍生物。结果与结论:分别用FT-IR1、H NMR1、3C NMR和元素分析对其进行了表征。用广角X射线衍射(wide angle X-ray diffraction,WAXD)、差示扫描量热法(differential scanningcalorimetry,DSC)和溶解度试验对其物理性质进行了分析。改性后的壳聚糖衍生物的水溶性较壳聚糖有了较大的改善。制得的6-O-琥珀酰-N-半乳糖化壳聚糖衍生物可作为潜在的肝靶向载体材料。

AIM:To synthesize and characterize O-succinyl-N-galactosylated chitosan derivatives.METHODS:The efficient procedure to prepare 6-O-succinyl-chitosan derivative (SCS) was established by using a three-step reaction. Phthaloyl group was firstly chosen as the protection group for the amino group of chitosan,and O-succinylation was completed then.Protection group was removed finally by using hydrazine hydrate.To produce galactosylated 6-O-succinyl chitosan (Gal-SCS),lactobionic acid was added and galactose group was introduced into the amino groups of SCS. Lactosaminated 6-O-succinyl-chitosan (Lac-SCS) was prepared through reaction of SCS and α-lactose,followed by reaction with KBH_(4). RESULTS AND CONCLUSION:The degree of substitution of succinylation,galactosylation and lactosamination were stipulated to be 30%,3% and 3.4%,respectively. The chemical structures of the novel 6-O-Succinyl-N-galactosylated chitosan derivatives were characterized by FT-IR,()^(1)H NMR,()^(13)C NMR and elemental analysis.The physical properties were analyzed by wide angle X-ray diffraction (WAXD),differential scanning calorimetry (DSC),and solubility test. It indicated that the chitosan derivatives show much better solubility in water after modification.6-O-Succinyl-N-galactosylated chitosan derivatives may be used as potential carrier material for hepatocyte-targeting.