Lamivudine And Synthesis Of Histamine H3 Receptor Antagonists

This paper is made up of the synthesis of Lamivudine and histamine H₃ receptor antagonist intermediate.The first part is on the synthesis of Lamivudine,whose chemical name is 2-deoxy-3-thiacytidine(2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone. It is a new kind of anti-HIV agent from nucleoside,which is produced by the Biochem Pharma Company in Canada.It inhibits the DNA synthesis of HBV via decreasing the bio-activity of DNA polymerase that depended on RNA.It may be useful in treatment of all kinds of hepatitis B.Its chemical properites, pharmacokinetic feature,mechanism of action,clinical uses,adverse drug reactions, and drug resistance are reviewed.We have compared about many synthesis routes of Lamivudine and have explored a new route to approach the terminate,which is from menthol and glyoxylic acid hydrate to 1-menthyl glyoxylate hydrate by esterification reaction.This intermediate can be reacted to(2R,5R)-5-Hydroxy-[1,3]oxathiolane-2-carboxylic acid,2S-isopropyl-5R-methyl-1R-cyclohexyl ester with dithianediol.Then we can get Lamivudine with acetylation,coupling and anhydrous reduction.Though trying different reaction conditions,reaction and proportions,we found a better process routes,which can get a high yield and a lower cost and is a safe process.This process route which needs simple raw materials is easy to industrial production.The structure of products was Verificated by ¹HNMR,¹³CNMR and MS.The other part is on the synthesis of the compound 2-Chloro-6-trifluoromethyl-quinoline, which is an important intermediate of histamine H₃ receptor antagonist. The histamine H₃ receptor plays a role in modulating the release,synthesis and metabolism of histamine in the Central nervous system,and it also takes part in the process of regulating the release and metabolism of many other neurotransimitters.So H₃ receptor antagonists will probably become a novel kind of medicine for attention -deficit hyperactivity disorder.Alzheimer's diseases and so on.This paper simply introduces the distribution of H₃ receptor and its functions,then concerns mainly the research background of H3 receptor antagonists. References mentioned 3,3-diethoxypropionate could be raw material,which can synthesis this intermediate by hydrolysis,chloride,and so on,five-step reaction total. This paper based on this process,and improved the reaction conditions,then we can get high yield.Owing to time constraints,further optimization is on going.