替诺福韦合成工艺的优化及抗菌活性研究

Synthesis optimization and antibacterial activities of tenofovir

为了优化替诺福韦合成工艺,以腺嘌呤和(R)-碳酸丙烯酯为起始原料,经开环缩合、取代、水解得到替诺福韦。通过高效液相色谱法(HPLC)监控整个反应过程,其中开环缩合的最佳反应条件为反应温度120℃,反应时间22 h;取代的最佳反应条件为反应温度60℃,反应时间6 h;水解的最佳反应时间20 h。在最优化条件下总收率达69.2%。通过紫外-可见吸收光谱和荧光发射光谱探讨其光物理性能,发现可以根据不同化合物的荧光发射波长差异来监测反应方向和反应程度;通过抗菌活性测试,发现对低浓度的金黄色葡萄球菌有一定的抗菌活性。该合成工艺实现了副产物回收套用,节约生产成本,提高产能。

To optimize the synthetic process of tenofovir,we synthesized tenofovir using adenine and(R)-propylene carbonate as starting materials through ring-opening condensation,substitution and hydrolysis.The processes of reactions were monitored by using high performance liquid chromatography.The best synthesis conditions for ring-opening condensation and substitution reaction were at 120℃for 22 h and at 60℃for 6 h,respectively.The best reaction time of hydrolysis is 20 h.The total yield is 69.2%under optimal conditions.The photophysical properties were investigated by UV-vis absorption spectroscopy and fluorescence emission spectroscopy,and the direction and extent of reaction can be monitored according to the wavelengths of fluorescence emission of different compounds.Tenofovir shows certain antibacterial activities against Staphylococcus aureus at a low concentration.This synthetic process realizes the by-product recovery and application,saves the production cost,and improves the production capacity.