| A Adefovir dipivoxil (ADV) is an oral prodrug of acyclic nucleotide monophosphonate ester analogue. It turns quickly to adefovir which has antiviral activity after oral absorbtion. This thesis is focus on the synthetic processes of 9-(2-phosphonomethoxyethyl) adenine (PMEA) and adefovir dipivoxil.Adefovir dipivoxil was synthesized from adenine and phosphorus trichloride as the starting materials. Diethylphosphite was prepared from ethanol and phosphorus trichloride at mole ratio of 3.3:1 with the droping temperature at 5-10℃, and reacted under room temperature. Hydroxymethyl diethylphosphonate was synthesized from diethylphosphite and paraformaldehyde at mole ratio of 1:1.33 in refluxing toluene, and then reacted with p-toluenesulfonyl chloride at mole ratio of 0.89 between -5 to 0℃to form diethyl p-toluenesulfonyloxymethylphosphonate. 9-(2-hydroxyethyl) adenine was prepared from adenine and ethylene carbonate at mole ratio of 1:1.11 in refluxing DMF, and reacted with sodium tert-butoxide firstly at room temperature, then condensated with p-toluenesulfonyloxymethylphosphonate at mole ratio of 1.4 times at -10-0℃to form 9-(2-diethylphosphonomethoxyethyl)adenine, which hydrolyzed with trimethylchlorosilane at mole ratio of 6 times in refluxing butyronitrile to form adefovir. Finally, adefovir dipivoxil was prepared from adefovir and chloromethyl pivalate at mole ratio of 1:5 through condensation reaction at room temperature following 50-60℃. The total yield of adefovir dipivoxil was 17.3% from adenine.In the new synthesizing process, the materials and reagents are commonly available. In preparing 9-(2-hydroxyethyl) adenine, ethanol absolute replaced toluene, and decreased the toxic environment. At the same time, the continuous extraction makes the operating process smoothly. The reactive conditions are geniality and suitable to the scale-up production. Trimethylchlorosilane with lower price replaced trimethylbromosilane with high price, and decrease the production cost.
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