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目的合成抗病毒药物富马酸替诺福韦酯并进行工艺改进。方法以亚磷酸二乙酯和多聚甲醛为原料,经缩合、酯化反应制得对甲苯磺酰氧甲基膦酸二乙酯(4);再以(S)-缩水甘油为起始物,经氢化还原、缩合反应制得(R)-碳酸丙烯酯(7),7与腺嘌呤反应合成(R)-9-(2-羟丙基)腺嘌呤(8),8经醚化、水解反应得到替诺福韦(10),再经氯甲基碳酸异丙酯酯化、与富马酸成盐得到目标化合物。结果与结论目标化合物的结构经MS、1H-NMR谱予以确证,该合成路线的总收率提高到30.4%(文献报道的最高收率为21%)。
Objective To synthesize tenofovir disoproxil fumarate and improve the process. Methods Diethyl p-toluenesulfonyloxymethylphosphonate (4) was prepared by condensation reaction and esterification reaction using diethyl phosphite and paraformaldehyde as starting materials. Starting from (S) -glycidol (R) -propylene carbonate (7) was synthesized by hydrogenation reduction and condensation reaction, 7 was reacted with adenine to synthesize (R) -9- (2-hydroxypropyl) Hydrolysis reaction to tenofovir (10), followed by chloromethyl isopropyl carbonate esterification, and fumarate salt to give the target compound. Results and Conclusions The structure of the target compound was confirmed by MS and 1H-NMR spectra. The overall yield of the synthetic route increased to 30.4% (highest reported in the literature was 21%).