T614衍生物的合成和阿司匹林及其衍生物的糖基化结构修饰研究

【作者】 朱前进；

【导师】 方志杰；

【作者基本信息】 南京理工大学 ， 生物化工， 2004， 硕士

【摘要】 本论文由两部分组成，即T614衍生物的合成和阿司匹林及其衍生物的糖基化结构修饰研究。 概述了非甾体抗炎药环氧酶-2抑制剂的研究进展，设计以β-萘酚烃化、氨基对甲苯磺酰化及苯环乙酰化对T614的中间体进行结构修饰，合成出了1个T614衍生物及16个中间体侧链修饰物，为寻找具有优化活性的先导物进行了探索性研究。 论文首先实验打通了合成T614衍生物的路线，由4-氯-3-硝基茴香醚出发经过七步全合成反应得到最终产品——3-甲酰胺基-6-苯氧基-7-对甲苯磺酰胺基苯并吡喃酮，在参考原始文献的基础上作出了出色的改进和创新，获得成功。 为对阿司匹林类化合物的结构及活性进行改造和优化，本论文采用乙酰基保护的溴代葡萄糖和水杨酸及其衍生物在相转移催化剂作用下反应，制得的糖苷再经乙酰化或催化氢化后乙酰化和脱乙酰化，实验合成了8个阿司匹林及其衍生物的葡萄糖基化修饰物及天然产物水杨苷。实验方法简便、重现性好，收率高，有较大实用价值。 对上述化合物利用高效液相色谱分析了纯度，并经红外光谱、核磁共振谱、质谱表征和结构确证。更多还原

【Abstract】 This thesis consisted of two sections, the synthesis of T614’s derivatives and studies on the structure modifying of Aspirin and its derivatives in carbohydrate.At this article we briefly summarized the progress in research of the Non-steroidal Anti-inflammatory Drugs - Cyclooxygenase-2 inhibitors, designed on the structure modifying of T614 by p-naphthol alkylation, anmino tosylation and benzol acetylation, mainly prepared one derivative of T614 and 16 lateral-chained structure modified compounds of its parted intermediates, the exploratory research had been done in order to search after the lead compounds possessing improved biological activities.The novel methods for the synthesis of T614’s derivatives were described, the total synthetical process included seven steps from 4-chloro-3-nitroanisole in which some improvements and innovations of the methods compare to the reference were worked out. In the end, we obtained the termination-product with high overall yield-3-(acylamino) -6-phenoxy-7-(p-tolylsulfonylamino) -4H-1 -benzopyran-4-one.To modify the structure and optimize the activities of Aspirin, a series of glucosides of Aspirin and its derivatives also natural product-Salicin were prepared via using bromo-glucose protected by acetyl and salicylic acid and its derivatives reacted by way of phase transfer catalysis, then applied the acetylation or catalytic hydrogenation before acetylation and deacetyltion to the corresponding acquired glucosides. These methods were proved to be relatively simple and stable with high yields and superior practical value.The purities of most compounds above were analyzed by HPLC, Their structures were confirmed and characterized by MS, NMR and IR.更多还原