9 - 〖 2 - (phosphono-methoxy) ethyl〗 Synthesis of adenine.docVIP

 PAGE \* MERGEFORMAT 7 9 - 〖 2 - (phosphono-methoxy) ethyl〗 Synthesis of adenine Authors: Lun Xiang, Zhang, Luo, FU Xiao-Zhong [Keywords:] Hepatitis B; adenine; adefovir; Drug Synthesis 9 - 〖 2 - (phosphono-methoxy) ethyl〗 adenine, adefovir is a kind of antiviral activity of acyclic nucleoside phosphonic acids, their double-pivaloyl methyl ester prodrug acyl oxygen adefovir 2 imidacloprid furosemide ester (adefovir dipivoxil) was developed by Gilead Sciences Inc., following FDA approval of lamivudine after the first two small-molecule anti-HBV drugs [1]. Pharmacodynamic studies have shown that adefovir two imidacloprid furosemide esters in vitro and in vivo of wild-type and mutation-resistant hepatitis B virus have a strong inhibitory activity [2]. Clinical studies have shown that the drug can significantly improve the properties of the liver in patients with lower serum HBV-DNA and transaminase levels, increase e antigen (HBeAg) conversion rate of [3]. In order to obtain raw materials to the next step the structure of adefovir derivative transformation, synthesis of the compound, compared with the reported method can more effectively improve the yield of the target compounds to reduce the impurities generated [4]. A synthetic route Adefovir is currently reported in the literature (structure see Figure 1) Synthetic Route: 2 - chloroethyl chloro-3-methyl ether and isopropyl phosphite by Michaelis-Arbuzov rearrangement reaction of 2 - chloro-ethoxy methylphosphonic acid 2 isopropyl ester, derived from material with adenine in the presence of cesium carbonate condensation reaction of 9 - 〖 2 - (phosphono-methoxy)-ethyl〗 adenine diisopropyl ester, which is handled by three bromide silane ultimately be the target compounds adefovir [4]. Used in the synthesis of 2 - chloroethyl chloromethyl ether expensive; another 2 - chloro-ethoxymethyl isopropyl ester phosphonic acid condensation reaction with the adenine target product yield lower, a lot of impurities, and