新型京尼平衍生物的合成、表征及抗糖尿病活性

为了寻找新型的抗糖尿病分子，从京尼平出发，经过甲基化（苄基化）、甲磺酰基取代、叠氮基取代和还原等4步反应得到含有活泼胺基的2个母核化合物. 这2个母核化合物与不同的酰氯反应，共得到13个新的京尼平衍生物，总收率41%~63%，其结构经核磁共振、质谱和元素分析确认. 活性测试结果表明，所有目标化合物在10 mmol/L 浓度下都有一定的抗糖尿病活性，其中化合物10f对二肽基肽酶4（DPP Ⅳ）的抑制率达31.2%.

Synthesis,Characterization and Antidiabetic Activities of Novel Genipin Derivatives

Diabetes has become the third major diseases threat to human's health and safety after cancer, cardiovascular and cerebrovascular diseases. The currently used drugs are difficult to completely cure the disease, and the long-term use is easy to produce side effects and drug resistance. So, it is very important to research and development a new kind of drug to treat the diabetes. The extract of gardenia and fruit containing the active ingredient genipin showed a very good effect in the traditional Chinese medicine treating the diabetes. In order to find novel anti-diabebes molecules, two core compounds containing amine group were synthesized from the commercial available genipin by methylation(benzylation), substitution with methylsulfonyl chloride followed by sodium azide and reduction. Thirteen novel compounds were obtained by reacting the two core compounds with a variety of acyl chlorides. The total yields were between 41% and 63%. Their structures were characterized by NMR, ESI-MS and elemental analysis and anti-dibiatic activities were evaluated by DPP Ⅳ assay at a concentration of 10 mmol/L. The results showed that all the title compounds exhibited certain extent inhibitory activities against DPP Ⅳ. Among them, compound 10f showed higher inhibitory rate up to 31.2%.