三氯乙酰亚胺酯法合成紫草素-1′-O-β-D-吡喃葡萄糖苷

目的:采用三氯乙酰亚胺酯法合成紫草素-1′-O-β-D-吡喃葡萄糖苷。方法:以β-D-吡喃葡萄糖为起始原料制得糖基供体2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖酰基2,2,2-三氯乙酰亚胺酯,然后与紫草素反应得1-(1-(5,8-二羟基-1,4-萘醌-2-基)-4-甲基-3-戊烯氧基)-2,3,4,6-四-O-乙酰基-β-吡喃葡萄糖苷,最后在甲醇钠/甲醇体系下醇解脱去乙酰基得到目标化合物,采用核磁共振波谱(NMR)和电喷雾-质谱(ESI-MS)表征其结构。结果:NMR和ESI-MS鉴定目标化合物为紫草素-1′-O-β-D-吡喃葡萄糖苷。三氯乙酰亚胺酯法合成紫草素-1′-O-β-D-吡喃葡萄糖苷总收率为38.9%,HPLC测定纯度为96.7%。结论:本方法合成紫草素-1′-O-β-D-吡喃葡萄糖苷具有高立体选择性和高收率的优点,为紫草素糖基化修饰产物的化学合成提供了参考。

二甲吡唑联苯并噻唑的合成及抗惊厥活性研究

根据药物设计原理,设计合成了一系列二甲吡唑联苯并噻唑衍生物并且研究其抗惊厥活性。实验结果表明:在所有衍生物中,当取代基为烷氧基且碳链长度为4和5时化合物表现出短时效抗惊厥活性,而碳链继续延长或是用苄基取代时,活性消失。这说明丁氧基和戊氧基取代时化合物可以透过血脑屏障进而发挥作用。安全性评价显示该系列化合物未表现出明显的神经毒性。

Enzymatic biosynthesis of novel neobavaisoflavone glucosides via Bacillus UDP-glycosyltransferase

The present study was designed to perform structural modifications of of neobavaisoflavone(NBIF), using an in vitro enzymatic glycosylation reaction, in order to improve its water-solubility. Two novel glucosides of NBIF were obtained from an enzymatic glycosylation by UDP-glycosyltransferase. The glycosylated products were elucidated by LC-MS, HR-ESI-MS, and NMR analysis. The HPLC peaks were integrated and the concentrations in sample solutions were calculated. The MTT assay was used to detect the cytotoxic activity of compounds in cancer cell lines. Based on the spectroscopic analyses, the two novel glucosides were identified as neobavaisoflavone-4′-O-β-D-glucopyranoside(1) and neobavaisoflavone-4′, 7-di-O-β-D-glucopyranoside(2). Additionally, the water-solubilities of compounds 1 and 2 were approximately 175.1-and 4 031.9-fold higher than that of the substrate, respectively. Among the test compounds, only NBIF exhibited weak cytotoxicity against four human cancer cell lines, with IC50 values ranging from 63.47 to 72.81 μmol·L^(-1). These results suggest that in vitro enzymatic glycosylation is a powerful approach to structural modification, improving water-solubility.