唾液酸酶检测剂(X-Neu5Ac)的合成  

Synthesis of Sialidase Detection Agent(X-Neu5Ac)

作　　者：雷雄[1] 朱晨辉[1] 郭宏垚 王小静[1] 胡薇月 王锋[1] 李稳宏[1] 

机构地区：[1]西北大学化工学院,西安710069 [2]陕西省产品质量监督检验研究院,西安710048

出　　处：《高等学校化学学报》2017年第3期398-402,共5页Chemical Journal of Chinese Universities

基　　金：陕西省教育厅服务地方专项计划项目(批准号:14JF026);陕西省可降解生物医用材料重点实验室项目(批准号:14JS102)资助~~

摘　　要：以唾液酸为起始原料,在浓硫酸催化下进行甲酯化反应得到唾液酸甲酯,收率比文献方法提高了20%以上;再通过酰氯反应制得化合物4,收率由86.4%提高到98.9%;化合物4于四氢呋喃(THF)中在氢化钠作用下与化合物6进行缩合反应,最后在MeONa醇解与碱作用下水解得到目标产物唾液酸酶检测剂X-Neu5Ac.该合成过程采用浓硫酸催化的方法得到化合物2,原料易得,操作更安全简单,避免了使用昂贵的树脂或者危险性很高的重氮甲烷.在酰氯反应中采用一锅法同时实现了乙酰基保护和氯代反应.另外,对关键中间体7的合成反应条件进行了单因素实验优化,获得了最佳合成条件:反应温度为室温(25℃),加入溶剂量为每g底物20 m L溶剂,反应时间为10 h.通过X-Neu5Ac活性成分的应用研究,发现检测所得产物的稳定性和显色灵敏性均达到要求.采用~1H NMR,ESI-MS和HPLC-MS对产物进行了结构表征.The sialic acid methyl ester was synthesized via the methanol esterification of sialic acid under the catalysis of concentrated sulfuric acid, and yield increased by 20% compared with all previously reported literatures. In the following acid chloride reaction, the yield of compound 4 increased from 86.4% to 98.9%. Compound 4 was condensed with compound 6 in the presence of sodium hydride in tetrahydrofuran（THF） and then was hydrolyzed by MeONa to obtain the target product （X-Neu5Ac）. The process adopted the catalytic method of concentrated sulfuric acid to get compound 2. The results indicate that the accessible raw material and safe operation avoided the use of expensive resin and the exist of dangerous diazomethane. Meanwhile, the one-pot method in acid chloride reaction benefited the reaction of acetyl protection and chlorination. As the key intermediate, the synthesis condition of compound 7 was optimized by single factor experiment to obtain the optimal reaction condition： the reaction temperature of 25 ℃, reaction concentration of 200 mL solvent per 10 g substrate, the reaction time of 10 h. By detecting the active ingredient in X-Neu5Ac, the stability and color sensitivity of products met relevant requirement and its structural properties were characterized by means of 1H NMR, ESI-MS and HPLC-MS.

关 键 词：唾液酸 X-Neu5Ac 关键中间体 显色 

分 类 号：O621.25[理学—有机化学]