Lamivudine diastereoselective synthesis method

A technology of lamivudine and synthetic method, which is applied in the direction of drug combination, digestive system, organic chemistry, etc., can solve the problems that are not conducive to the health of operators, strong triethylamine, expensive raw materials, etc.
CN101544632AActive Publication Date: 2009-09-30湖南千金湘江药业股份有限公司
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
湖南千金湘江药业股份有限公司
Publication Date
2009-09-30

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Abstract

A lamivudine diastereoselective synthesis method, which takes chiral auxiliary agent L-menthol as the initial material, synthesizes trans-5-hydroxyl-1, 3-oxygen thiacyclopentane-2-carboxylic acid-(1'R, 2'S, 5'R) menthol ester under the action of concentrated sulfuric acid, choose triethanolamine to obtain trans-isomer trans-5-hydroxyl-1, 3-oxygen thiacyclopentane-2-carboxylic acid-(1'R, 2'S, 5'R) menthol ester, and let the trans-isomer to react with acylating agent to obtain trans-5-acetoxy-1, 3-oxygen thiacyclopentane-2-carboxylic acid-(1'R, 2'S, 5'R) menthol ester, glycosidate with cytosine under the action of alkali to obtain 5S-cytosine-1'-radical-1, 3-oxygen thiacyclopentane-2-carboxylic acid-(1'R, 2'S, 5'R) menthyl ester, and then deoxidize with a deoxidizer, and salifying with aspirin, to ionize and liberate lamivudine. Since triethanolamine is added as in the course of reaction interconverting agent, the yield of lamivudine is increased greatly. Aspirin is added in the course of reaction, so that the lamivudine forms an aspirin salt that has poor water solubility, and therefore can effectively separate and liberate lamivudine from the medium.
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Description

Technical field:

[0001] The invention relates to a production method of nucleoside analogs, in particular to a diastereoselective synthesis production method of lamivudine. Background technique:

[0002] Lamivudine (lamivudine, Zeffix, chemical name: 2,3-dideoxy-3-thiocytosine, referred to as 3TC) is a nucleoside analog and a viral DNA reverse transcriptase inhibitor. For chronic hepatitis B, the treatment of patients with proven decompensated liver disease or histologically confirmed active and (or) fibrosis. Its chemical structure is:

[0003]

[0004] Lamivudine, a novel deoxynucleoside analog, is (2R-cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl )-2(1H)-Pyrimidinone is one of the four optical isomers of the cis left-handed optical enantiomer, which is a new generation of nucleoside antiviral drugs superior to the anti-HIV drug AZT. It has obvious effects on human immunodeficiency virus HIV and has been approved by dozens of countries to treat AIDS. Since 199...

Claims

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