2-O-β-D-葡萄糖基-L-抗坏血酸及其类似物的合成和抗氧化性研究

Antioxidants play an important role in food safety and preservation, the prevention and treatment of human disease. In recent years, natural and highly effective antioxidants are pursued in the field of chemistry, medicine, pharmaceutics and food industry. 2-O-β-D-glucosyl-L-ascorbic acid (AA-2βG) is a natural vitamin C-derived glycoside, which is found in the Chinese traditional medicine Goji berry fruit. It was demonstrated that AA-2βG is useful as a pro-vitamin C and keeps long-time efficiency in vivo. Moreover, AA-2βG shows stronger stability and antioxidative activity than that of vitamin C. However, the current method of extraction of AA-2βG is insufficient. What is more, the concrete mechanism that how AA-2βG scavenges free radicals is still ambiguous. Thus, it is necessary to synthesize this kind of compound and deeply investigate their biological activities including mechanism. In this project, AA-2βG and its analogues are designed and would be chemically synthesized through simple and highly effective method. The abilities of scavenging free radicals, tyrosinase inhibitory activity in vitro and antioxidant activity in vivo of these compounds would be examined to understand structure-activity relationship. This research would provide the basic data to further study on antioxidative mechanism, biological activity of this kind of compounds and the development of drugs.

抗氧化剂在食品安全和保鲜、人体保健与疾病防治等方面都有重要作用，近年来，开发天然高效的抗氧化剂成为化学、医学、药学和食品科学的研究热点。作为从传统中药枸杞子中分离出的糖苷类化合物，2-O-β-D-葡萄糖基-L-抗坏血酸（AA-2βG）是一种稳定的维生素C前体物质，其清除自由基能力比维生素C更强，效果温和持久。然而，目前从枸杞子中提取AA-2βG远不能满足对其深入研究和开发应用的需要，且其具体的抗氧化机制尚未完全确证，因此，围绕这一类化合物的合成及活性机理研究意义重大。本项目设计简便高效的化学方法合成AA-2βG，拟利用此策略合成一系列类似物，考察并系统比较这类物质的体外清除自由基能力、抑制酪氨酸酶活性和体内抗氧化活性，探索其抗氧化机制，开展药物活性与分子结构间的构效关系研究，为开发安全高效的抗氧化剂提供分子水平的基础数据。

2-O-β-D-葡萄糖基-L-抗坏血酸（AA-2βG）是从枸杞中分离得到的一种天然抗坏血酸糖苷化合物，本项目通过化学方法合成了AA-2βG，及其类似物2-O-β-D-半乳糖基-L-抗坏血酸和3-O-β-D-葡萄糖基-L-抗坏血酸。以商品化的阿卡波糖作为阳性对照，研究了三种抗坏血酸糖苷对酿酒酵母α-葡萄糖苷酶和猪胰腺α-淀粉酶的活性影响，结果显示，三种抗坏血酸糖苷对α-葡萄糖苷酶有显著的抑制作用，对α-淀粉酶抑制作用不明显，动力学研究和分子对接实验均证实了三种糖苷对于α-葡萄糖苷酶是竞争性抑制机理。通过活体实验考察了3种化合物对糖尿病小鼠体内的血糖影响，发现3种化合物对分别服用麦芽糖和淀粉的糖尿病小鼠的餐后血糖波动有明显的控制作用，以上研究结果说明合成的三种抗坏血酸糖苷具有作为α-糖苷酶抑制剂降血糖药物开发的潜质。