盐酸拓扑替康的超声波辐射合成及其表征  

Study on the Synthesis of Topotecan Hydrochloride under Ultrasound Irradiation and its Characterization

作　　者：祖元刚[1] 张莹[1] 陈小强[1] 付玉杰[1] 李庆勇[1] 

机构地区：[1]东北林业大学森林植物生态学教育部重点实验室,黑龙江哈尔滨150040

出　　处：《高校化学工程学报》2007年第6期1080-1083,共4页Journal of Chemical Engineering of Chinese Universities

摘　　要：盐酸拓扑替康—一种水溶性的喜树碱衍生物,是拓扑异构酶Ⅰ抑制剂,广泛用于癌症治疗。首先以喜树碱为原料通过光化重排反应合成10-羟基喜树碱,然后研究了10-羟基喜树碱在超声波辐射下通过Mannich反应合成盐酸拓扑替康的各种影响因素,考察了超声反应温度、反应频率和反应时间对收率的影响,并通过单因素试验确定了优化的工艺条件,得出超声波辐射合成盐酸拓扑替康的最佳工艺条件是:超声反应温度为40℃,反应频率为40kHz,反应时间120min,在这个条件下进行的反应收率为95.54%,并对得到的化合物进行了IR、MS、1H-NMR分析,结构得到了表征。与传统的方法相比,此方法安全、易操作,既缩短了反应时间,又提高了反应收率,更适合工业化生产。As an inhibitor of topoisomerase Ⅰ , the topotecan hydrochloride, a soluble analogue of camptothecin, is broadly used to treat cancer. Here a new procedure for rapid synthesis of topotecan hydrochloride from 10-hydroxycamptothecin via Mannich reaction with the help of ultrasound was presented. The influences of reaction temperature, the frequency of ultrasound used and reaction time on the reaction yield were investigated, and through the single factor tests, the optimum reaction conditions were determined as follows： reaction temperature of 40 ℃, ultrasonic frequency of 40 kHz and reaction time of 120 min. Under above reaction conditions, the average yield of topotecan hydrochloride can reach up to 95.54%, and the obtained compounds were characterized by Fourier transform infrared spectroscopy, mass spectrum and nuclear magnetic resonance. The experimental results show that, compared with the traditionally used Mannich reaction with stirring, the proposed new procedure of using ultrasound is safer and easy to operate, using it not only the reaction time is shortened, but also the reaction efficiency and yield are enhanced. Therefore it is more suitable to be used for industrial production.

关 键 词：喜树碱 盐酸拓扑替康 超声波辐射 合成 

分 类 号：TQ021.9[化学工程] R914.5[医药卫生—药物化学]