3,6-二氨基甲壳素/壳聚糖的设计、合成及抑真菌活性研究

Chitosan, a kind of renewable, abundant natural cationic polysaccharide, could effectively inhibit growth of many harmful microorganisms. It has already been widely studied and reported that chitosan is non-toxic, biodegradable, and biocompatible, which make it a promising candidate to be developed as an antifungal agent. Based on the importance of amino to the antifungal activity of chitosan, this project plans to increase the number of amino groups on the chitosan by chemical modification. Amino group will be introduced into C-3 and C-6 position of chitin and chitosan, which changes their structure. The designed amino chitin and amino chitosan will be synthesized and chemically modified. After that, their antifungal activity against phytopathogens will be estimated by hypha measurement in vitro. This project first research the relationship between number of amino and antifungal activity of chitosan derivatives. The influence of amino on antifungal activity of chitosan will be estimated, and the antifungal mechanism will be enhanced. In this work, we will break the limitation of chitosan with only one amino group at C-2, and provide a novel kind of amino saccharides. The results will enrich the type of amino chitosan derivatives, improve the antifungal activity of chitosan, and prompt the development of other amino saccharides.

壳聚糖是一种安全无毒、生物量大、可自然降解的天然阳离子氨基多糖，能有效抑制多种致病性微生物的生长，有望被开发成绿色抑菌剂。基于氨基对壳聚糖抑菌活性的重要影响，本项目拟通过化学修饰增加壳聚糖上氨基的数量，从改变壳聚糖结构的角度突破每个糖单元只有一个氨基的限制，在甲壳素和壳聚糖的C-3和C-6位引入氨基，设计合成氨基甲壳素和氨基壳聚糖；并对其氨基做进一步化学修饰，测试这些壳聚糖衍生物的抑菌活性。本项目将对壳聚糖分子中氨基的位置、数量与抑真菌活性之间的关系进行系统研究，总结氨基对壳聚糖抑真菌活性影响的规律，完善壳聚糖的抑菌机理。本项目打破壳聚糖固有的氨基数量少、位置固定的现状，为相关壳聚糖衍生物的开发提供更多新的修饰位点与产品开发可能性；同时为提高壳聚糖抑菌活性提供新的研究思路；在丰富氨基壳聚糖衍生物种类、提高壳聚糖抑菌活性、推动氨基多糖的发展等方面具有重要意义。

本课题基于氨基对壳聚糖和甲壳素抑菌活性的重要影响，通过化学修饰增加壳聚糖和甲壳素上氨基的数量，从改变壳聚糖和甲壳素结构的角度突破每个糖单元只有一个氨基的限制，在甲壳素和壳聚糖的C-3和C-6位引入氨基，设计合成氨基甲壳素和氨基壳聚糖；并对其氨基做进一步化学修饰，测试这些壳聚糖衍生物的抑菌活性。对壳聚糖分子中氨基的位置、数量与抑真菌活性之间的关系进行研究，完善壳聚糖的抑菌机理。打破壳聚糖固有的氨基数量少、位置固定的现状，为相关壳聚糖衍生物的开发提供更多新的修饰位点与产品开发可能性；为丰富氨基壳聚糖衍生物种类、提高壳聚糖抑菌活性、推动氨基多糖的发展提供一定的理论指导。发表英文SCI文章12篇；申请国家发明专利9项，已授权7项。主要研究成果如下：.(1) 根据文献及课题组前期工作基础，设计并合成了氨基甲壳素、二氨基甲壳素和6-氨基壳聚糖，并对其进行抑真菌和抗氧化活性测试。结果表明引入氨基后，氨基甲壳素、二氨基甲壳素和6-氨基壳聚糖具有比甲壳素和壳聚糖更好的抗氧化能力和抗真菌活性。相关成果已发表在“International Journal of Biological Macromolecules”和“Carbohydrate Polymer”等期刊上。.(2) 在以上工作的基础上，对氨基甲壳素和氨基壳聚糖进行进一步的结构设计及化学修饰，制备了壳聚糖季铵盐和甲壳素季铵盐，并对其进行表面形貌、抑菌活性和抗氧化活性的研究测试。所得到的壳聚糖季铵盐和甲壳素季铵盐水溶性得到改善，而且抑菌活性和抗氧化活性进一步提高。相关成果已发表在“Polymer Chemistry”和“Carbohydrate Polymer”等期刊上。