嘌呤类核苷化合物的研究

【作者】 万碧莲；

【导师】 蒋鹏举；

【作者基本信息】 南京理工大学 ， 应用化学， 2004， 硕士

【摘要】 腺苷是一种重要的生物大分子，研究表明它有多种心脏保护作用，可以作为心脏病的治疗药物，还可以用于冠心病的诊断和愈后评价。以腺苷为原料合成的8—溴腺苷是重要的医药中间体，可以用于合成多种具有抗病毒活性和抗肿瘤作用的核苷类似物。 本文以四乙酰核糖和腺嘌呤为原料，采用三种方法合成β-腺苷。（1）熔融法，在减压高温的条件及碘的催化作用下用四乙酰核糖和碱基反应，再经脱酰基，合成腺苷。该法比较简单方便，但糖基化的立体选择性差，得到的产物是α-和β-构型的混合物，需要经过硅胶柱分离；（2）重金属法，用N⁶-苯甲酰基腺嘌呤的氯化汞盐与三乙酰氯代核糖反应得到产物，氯化汞在反应过程中起到催化剂作用。该法具有很好的立体选择性，得到的产物主要是β-腺苷，不需要经硅胶柱分离；（3）硅烷化法，将N⁶—苯甲酰基腺嘌呤经预先硅烷化后，不经分离即直接在SnCl₄的催化作用下与四乙酰核糖进行糖基化反应，操作简便，反应条件比较温和，但产品同样是混合物，需要经硅胶柱分离。 实验在合成腺苷的基础上探讨了8—溴腺苷的合成工艺：在乙酸钠的缓冲溶液中腺苷与溴发生选择性溴化反应，得到高产率的8—溴腺苷。更多还原

【Abstract】 As an important biological molecue, adenosine is widely used in iatrology as a clinical medicine to protect heart or treat coronary heart disease. 8-Bromoadenosine is a useful intermediate on the synthesis of some analogs of adenosine, which can restrain the virus’ vitality or tumour.Three methods are described to synthesize β-adenosine by using tetraacetyl -ribofuranose and adenine as two reactants. l)Fusion Method, tetraacetylriblfuranose and heterocycle base react in the precense of iodine by heating.Because of its shortage in stereoelective,the mixture of a- and P-adenosine is obtained after deacetylation and then needs to be separated through silicagel column. 2)Heavy metal method, P-adenosineis obtained by using chloromeruri N6-benzoyladenie and triacetylribo -furanosyl chloride as reagents in which chloromercuiri is used as catalyst. Because of its better stereoelective, silicagel column is not needed.3)Silylation method, Silylated N6-benzoyladenine without separation reacts with tetraacetylribofuranose, catalysted by SnCl4. It is not stereospecific and the product also needs to be separated through silicagel column regardless of the simple process and the moderate condition.Furthermore, the synthesis of 8-bromoadenosine of which the productivity is pretty high is also discussed by using adenosine and bromine reacting in the buffer solution ofNaOAc.更多还原