Large Scale Preparation of Cyclodextrin Linked Chitin Derivatives Having Potential Use for Biological Friendly Host-compounds

将壳聚糖与环糊精偶联，合成了能与多种有机化合物形成包合物的新型多糖衍生物。壳聚糖是由蟹壳的主要成分几丁质去n -乙酰化而成的氨基多糖，而环糊精是α -(1,4)-连接葡萄糖的环状低聚物。本研究发现（甲酰基甲基）-环糊精的还原性胺化反应有助于与壳聚糖的偶联。该方法适用于在均相反应体系中合成高分子量（bbb250000）环糊精连接壳聚糖。取代度（D.S.）根据起始环糊精衍生物的用量从7%到75%不等。在中性或碱性条件下，含dss> 30%的衍生物均可溶于水。使用模型客体化合物的初步光谱分析表明，它们形成包合物的能力（通过它们的解离常数来测量）几乎与未偶联的环糊精相同。以交联壳聚糖珠为原料，采用类似的偶联方法制备了具有高孔隙结构的不溶性环糊精连接壳聚糖。初步实验评估了这些高分子主体化合物在反相色谱、控释应用中的吸附剂、毛细管电泳中的假固定相以及化妆品中保护皮肤免受化学伤害的添加剂等方面的应用。将环糊精连接壳聚糖与乙酸酐在水中进行n-乙酰化反应，得到几乎定量产率的环糊精连接甲壳素。

Novel polysaccharide derivatives capable of forming inclusion complexes with various organic compounds have been synthesized by coupling chitosan with cyclodextrins. Chitosan is an amino-polysaccharide prepared by de-N-acetylation of chitin, a major component of crab shell, and cyclodextrin is a cyclic oligomer of alpha-(l, 4)-linked glucose. In the present study, reductive amination of (formylmethyl)-cyclodextrins was found useful for the coupling with chitosan. This method was applicable to the synthesis of high molecular weight (>250,000) cyclodextrin-linked chitosan in a homogeneous reaction system. The degree of substitution (D.S.) varied from 7 to 75% depending on the amount of the starting cyclodextrin derivative used. Derivatives with D.S.>30% were soluble in water under neutral or alkaline conditions. Preliminary spectroscopic analyses using model guest compounds suggested that their ability to form inclusion complexes (as measured by their dissociation constants) was almost the identical with that of the uncoupled cyclodextrin. Furthermore, insoluble cyclodextrin-linked chitosan with a highly porous structure was prepared by a similar coupling method using cross-linked chitosan beads. Preliminary experiments were conducted to assess the utility of these polymeric host compounds for reversed-phase chromatography, as adsorbents for controlled release applications, as a pseudostationary phase in capillary electrophoresis, and as additives in cosmetics to protect skin from chemical damage. N-acetylation of the resulting cyclodextrin linked chitosan with acetic anhydride in water gave cyclodextrin-linked chitin in almost quantitative yield.