Synthesis Of 2-amino-9-(3-acetoxymethylbutyl)purine And Its Application In Inactivating Environmental Virus

With industrial progress and development,environmental pollution is becoming more and more serious.Among them,the harm of virus and microorganism to the environment and human beings is especially worthy of attention and research.In this thesis,firstly,an analogue of antiviral drug Famciclovir,namely2-amino-9-(3-acetoxymethylbutyl)purine(1)was devised and synthesized.Next,the biological activities of 1 in inactivating environmental virus and microorganism was evaluated.The synthesis of 2-amino-9-(3-acetoxymethylbutyl)purine has not been reported in literatures yet.Firstly,we carried out the synthesis of 2-amino-9-(3-acet--oxymethylbutyl)purine.A synthetic route for 2-amino-9-(3-acetoxymethylbutyl)--purine was developed.Starting from readily available diethyl methylmalonate and1,2-dibromoethane,side chain diethyl 2-methyl-2-(2-bromoethyl)malonate was first smoothly prepared.The condensation of diethyl 2-methyl-2-(2-bromoethyl)malonate with 2-amino-6-chloropurine provided the key precursor 2-amino-6-chloro-9-[3,3-bis(ethoxycarbonyl)butyl]purine.2-amino-6-chloro-9-[3,3-bis(ethoxycarbonyl)--butyl]purine then underwent consecutive decarbethoxylation,reduction,acetylation and reductive dechlorination offering the target molecule 2-amino-9-Acetoxy(3-methylbutyl)purine.The six-step overall yield is 24%.2-Amino-9-(3-acetyl-butyl)purine,as a nucleotide antiviral drug,has potential applications in the inactivation of environmental viruses.Thus2-amino-9-(3-acetyl-butyl)purine was used to inactivate the indicator virus in environmental samples.The experiment selected MS2 as environmental indicator virus,and the factor including concentration,treatment time,pH were also discussed to optimize the chemical inactivation virus system.Meanwhile,the logarithm inactivation value(LIV)was used to evaluate the efficacy of virus inactivation.Results showed that the optimal inactivation condition of the experimental system was 5 mg/L of 2-amino-9-(3-acetyl-butyl)purine,30 min of the treatment time and 5.26 of pH.Under the above optimal conditions,the inactivation effect of synthesized 2-amino-9-(3-acetyl-butyl)purine was high.And the LIV could be decrease to 2.20 log10 which was in line with the National Drug Administration issued by the "removal/deactivation of virus technology and certification guidelines" requirements.