Anti-aids Drug Zidovudine, The Secretary Telbivudine And Functional Molecular Isostearic Acid Synthesis

The article includes two parts: one is the synthesis of Zidovudine and Stavudine,the other is the preparation of isostearic acid. 1, Synthesis of Zidovudine and Stavudine1) ZidovudineNow, Zidovudine is widely used as anti-aids drugs in china, which is a nucleoside analogues with reverse transcriptase ihibitive activity. In cells infected by virus, Zidovudine is transformed into AZT-TP by cells kinase with high affinity with HIV-RV, which can inhibit HIV-RV's activity and prevent HIV's replication.There are many reports about synthesis of AZT, and in these articles Ph₃CCl is often used. But it's expensive and Ph₃COH brought by Ph₃CCl is difficult to dispose. Therefore, the article used pivaloyl chloride to protect β-thymidine. Then after several reactions, O-bridge compound was obtained. The article solved the problem above and avoided the losses caused by intermediate purification, while pivaloyl chloride and mesyl chloride are cheap. This process increased the yield by 75% to 83% and reduced operation.During the later steps, when lithium chloride reacted with sodium azide, the reaction temperature was lowerd. The article avoided the exposure of NaN₃ when the reaction temperature was high and reduced the loss of intermediate by avoiding purifying it. In the process of deprotection, the article first removed (CH₃)₃COH boiling with water and then used HC1 to neutralize NaOH. After that, by extracting with solvent, NaCl was deprosed. The process above costs less than the method that uses resin. The article invented a processs to synthesize AZT which had the following advantages: less cost, simpler operation, better products and higher yield.2) StavudineStavudine was exploited by Bristol-Mayers Squibb corperation. As NTTIs, stavudine is one of the anti-aids drugs firstly coming into Chinese market. Beacuse Stavudine is less poisonous than AZT and can cure patients that AZT can't cure, and it has been the important part of anti-aids drugs.Now, Stavudine has been allowed to be preparated in China, but most synthesis method is complex and costs great. β-thymidine was choosed in the article as raw material to synthesize bimethylsulfonyl intermediate, then removed methylsulfonyl group, and controlled pH through adding LiOH droply. The article increased O-bridge yield by 67%-75.3%. Pure stavudine was recrystallized in suitable solvent and the yield was increased by 52.3%-57.2%. Thus, the article invented a kind of route which has the following advantages: simpler to operate, more economical, easier to produce. 2, Production of isostearic acidIsostearic acid is an isomer of stearic acid with branch.Isostearic acid's solubility, need of surface and moisture permeability are higher than stearic acid. Branch structure lows freezing point. Even under room temperature, isostearic is also liquid, which makes it easy to be manufactured into Industry product. Without containing double bonds, isostearic acid is more stable to oxygen than oleic acid.Processing the advantages above, isostearic acid is mainly used as material for cosmetic, lubricant, textile, paint and so on. The product using isostearic acid is better than the product using oleic acid and stearic acid.Now the preparation of isostearic acid has not been reported. The domestic need of isostearic acid is sufficied by import. So it is utmost important to synthesize it. Under 250～275℃ and with small pore catalyst like zeolites, oleic acid was changed into branched C18 acid and then transformed into isostearic acid through hydrogenation with lower IV. And The article made the suitable zeolite for isomerization and increased yield. The later experiments shew that under this condition the isostearic acid's quality was good, but the yield was lower. And this is need to be further researched.