Synthesis Of Nucleoside Anti-hepatitis B Drug Telbivudine And Its Prodrugs

Hepatitis B virus is the major reason which caused viral Hepatitis type B. It is reported that so far there are not less than 20 million people infected with hepatitis B virus (HBV) in worldwide, in all of these infections, approximately 3.5 million people will eventually become chronic carriers of hepatitis B virus. China is a high incidence of viral hepatitis B,in our legal infectious diseases, the incidence of hepatitis B virus infection is lower than the epidemic influenza and diarrhea. Hepatitis B serious impact human health, and brought a heavy financial burden to the family and the community. Hepatitis B virus patients are subject to a series serious impact in nursery, school, work, marriage and other aspects, which triggered a series of social problems, has become a major public health problem in China.Telbivudine has approved by the U.S. Food and Drug Administration to treatment of chronic hepatitis in 2006. Clinical studies have shown that telbivudine strong and selective inhibition of chronic hepatitis B virus DNA polymerase activity, telbivudine do not inhibition human cells of DNA polymerase, and do not produce serious adverse reactions. Therefore, telbivudine to the clinical treatment of chronic hepatitis B offers a new choice to the majority of hepatitis B patients has brought the gospel. In this paper, 2 - deoxy-D-ribose as starting materials,we synthesis telbivudine through different methods. In order to accomplish 2 - deoxy-D-ribose conformation from D to the L configuration conserve ,we use two different methods and get 2 - deoxy-L-ribose. Then through selectively into the ring, hydroxyl protection, chloride, coupling, deprotection we get the target compound telbivudine.We have synthesized two types of prodrugs on the basis of telbivudine:one is the 3'-O-acetyl-5'-O-Poly glycol ester telbivudine , 4 compounds; the other is 3′-O-Acetyl-5′-O-Phenyl-N-Alkylphosphramidates telbivudine,12 compounds.All of compounds have not been reported before.We tested for two types of prodrugs anti-HBV activity in which five compounds showed better anti-HBV activity than the positive control drug telbivudine in vitro. The present findings made them as attractive candidates for further studies...