葡萄糖氨基醌类的合成

Synthesis on Glucoseamino Quinones

由于一般小分子醌属于脂溶性化合物,常不溶于水,不能直接静脉给药,限制了其临床应用。为此在各类醌母环上设法引入亲水性葡萄糖氨基,增强醌分子极性和溶解性,改善母体结构的生物活性。本文探讨了氨基葡萄糖对含不同结构类型芳环的对、邻醌亲核加成合成反应的影响。以四氯苯醌、2,3-二氯-1,4-萘醌、1,4-萘醌、茜素、茜素红等醌类和氨基葡萄糖盐酸盐为主要原料,吗啡啉和糠胺等为辅料。氨基葡萄糖与等物质的量四氯苯醌反应后,主要生成一元葡萄糖氨基取代三氯苯醌(b),(b)再与等物质的量糠胺或吗啡啉反应,得到具有杂环结构的葡萄糖氨基苯醌(d)和(e)。氨糖与等物质的量2,3-二氯-1,4-萘醌反应可生成一元葡萄糖氨基取代萘醌(i)。而氨糖与等物质的量的1,4-萘醌、茜素及茜素红通过加成-氧化法可分别生成相应氨基醌(h)、(k)、(m)和(n)。加成-氧化法收率高于卤代醌取代法,分离操作相对简单。通过红外、紫外、质谱、核磁等检测手段对产物进行表征。

Because the general small quinone molecules are fat-soluble compounds. They are insoluble in water and can-not be directly intravenous administration. Thus their clinical application is limited. To enhance the quinone molecular polarity and solubility,improving the biological structure of the mother,the quinones mother ring were tried to introduce hydrophilic glucose amino. The nucleophilic addition reaction of the aromatic ring with different structure types and the effect of glucosamine on the ortho and para quinones were investigated respectively. Tetrachloroquinone ,2 ,3-dichloro-l , 4-naphthoquinone, 1,4-naphthoquinone,alizarin,alizarin red and glucosamine hydrochloride were used as a raw materi-al, morphine and furfurylamine were used as auxiliary material. First,glucosamine was reacted with an equimolar amount of quinones to obtain mono-glucosamino substituted trichlorobenzoquinone （b）. Then （b） was reacted with an equimolar amount of furfuryl amine or morpholine to produce the glucosaminobenzoquinones （ d） and （ e ） with a heterocyclic structure. The reaction between an equimolar amount of glucosamine and 2,3-dichloro-l ,4- naphthoquinone can generate a single glucosamino-substituted naphthoquinone （i）. Compounds （h） ,（k） ,（m） and （n） can be produced by the ad-dition-oxidation method of reaction between an equimolar amount of glucosamine and 1,4-naphthoquinone or alizarin or alizarin red. The yield of addition-oxidation method is higher than that of haloquinone method,and the separation opera-tion is relatively simple. All products were characterized by IR,UV,NMR and MS.