The Synthesis Of 9-[(2,3-Dihydroxypropoxy)Methyl]Guanine

9-[(2,3-Dihydroxypropoxy)methyl]guanine is one of the related substances of antiviral drug ganciclovir recorded in European Pharmcopoeia(Edition 8.0). This thesis provided two feasible synthetic routes for the synthesis of 9-[(2,3-Dihydroxypropoxy)methyl]guanine which can be used as a reference sample in the quality control of ganciclovir.In the first synthetic route, benzyl glycidyl ether was used as starting material. The ring opening of benzyl glycidyl ether under acidic condition gave diol product 3-benzyloxy-1,2-dihydroxypropane which then reacted with triphenylchloromethane furnishing the di-protected glycerol derivative intermediate 3-benzyloxy-2-hydroxy-1-triphenylmethyloxypropane. It was protected again with benzyl chloride to provide 2,3-dibenzyloxy-1-triphenylmethyloxypropane. Removal of the protecting trityl group in HOAc and subsequent chloromethylation of hydroxyl group and substitution with potassium acetate generated the key side chain compound 2,3-dibenzyloxy-1-acetoxymethyoxypropane. Next, condensation of 2,3- dibenzyloxy-1-acetoxymethoxypropane with N2,9-diacetylguanine catalyzed by p-toluenesulfonic acid monohydrate in N,N-dimethylformamide followed by hydrogenolysis of dibenzyl group and hydrolysis of N2-acetyl group offered target molecule 9-[(2,3-Dihydroxypropoxy)methyl]guanine.In the second synthetic route, allylic alcohol was used as starting material, side chain 2,3-diacetoxy-1-acetoxymethyoxypropane was first prepared through chloromethylation of hydroxyl group, substitution with potassium acetate, dihydroxylation of olefin and esterification with acetic anhydride. Next, condensation of 2,3-diacetoxy-1-acetoxymethoxypropane with N2,9-diacetylguanine catalyzed by p-toluenesulfonic acid monohydrate in N,N-dimethylformamide followed by hydrolysis with aqueous sodium hydroxide solution offered target molecule 9-[(2,3-Dihydroxypropoxy)methyl]guanine.Finally, the advantage and disadvantage with the two feasible synthetic routes for the synthesis of 9-[(2,3-Dihydroxypropoxy)methyl]guanine were discussed.