Enzymatic Synthesis of Nucleosides
一、Enzymatic synthesis of 5-methyluridine
As AIDs was pervading in the worldwide, the research and development of medicine possessing anti-HIV function became more and more important. Several nucleoside medicine approved by FDA revealed great advantage and essentiality.
5-methyluridine is the important intermediate in the chemical synthesis of anti-AIDS novel pharmacy---azidothymidine(AZT) or 2',3'-didehydro-2',3'-dideoxy-thymidime(d4T). Preveniently 5-MUR was chemical synthesized from inosine or tetraacetylribose and the production cost is about 150$/kg. However, if 5-MUR was synthesized by enzyme, the cost would reduced to $75/Kg, and there was no organic solvent demanded or no environment pollution.
If enzymatic synthesis of 5-methyluridine was successful, the price of AZT and d4T would be declined greatly. It would be much benefited to all HIV sufferer.
二、Enzymatic synthesis of 5-fluorouridine or Furtulon
Furtulon(5'-deoxy-5-fluorouridine) is recognized as the best anti-malignacey medicine international. The US patent of pharmacy was at term in 1994. It was applied as Four Novel species of medicine in Shanghai, Anhui and Guangzhou. Furtulon had severl characteristics, such as selective repression
of tumour, resistant of tumour transmission and improvement of ferocity body's fluid. It also had advantages of high curative effect, small side effect, prolongation of live and improvement of life's quality. It was widely used to therapy stomach cancer, rectum cancer, colon cancer, galactophore cancer, cervical cancer, ovary cancer and bladder cancer. It was also used to cure terminal malignancy. So this medicine was used high dosage and can be used for long time and it had large market.5-fluorouridine(5-FUR) is the intermediate of flutulon and mainly synthesized from uridine. In the chemical process, the cost of 5-FUR is above $1500/kg and the final cost of Furtulon was above $8000/Kg if the price of uridine is about $150/kg. But if FUR was synthesized with enzyme, any cheapness nucleoside could be used as raw material and through one step of reaction FUR could be obtained. For example, compare with chemical synthesis, cost of Futulon would be reduced 60% if guanosine($30/Kg) was used.
There was low cost, high yield and little pollution in the enzymatic synthesis of 5-FUR. This method was the research direction abroad. As far as know, the conversion yield of 5-FUR is only about 19% and the technique had no practicality. However in our laboratory, the conversion yield reached to 60% and the method had been applied patent.
As the same principle, if 5'-deoxyinosine or 5'-deoxyguanosien could be chemical synthesized, Futulon maybe enzymatically synthesized directly. The cost of production could decline to below $600/Kg. This techniques had been successed in development by our lab. We starved for investment to practise.
三、Enzymatic synthesis of other nucleosides
1。Enzymatic synthesis of ribavirin
The production cost would decline to below $60/Kg if guanosine or inosine was used as raw material. The conversion yield could reach above 85%.
2。Enzymatic synthesis of 2'-deoxy-5-fluorouridine
The conversion yield could arrive at above 50% if 2'-deoxyuridine and 5-FU were used.
3。Enzymatic synthesis of thymidine
The production cost of thymidine maybe only $200/kg if 2'-deoxyinosine was chemically synthesized as raw material and the conversion yield could achive above 50%.
4。Enzymatic synthesis of 2'-deoxynucleosides
The technique of chemical synthesis of thymidine had been industrialized. Thus if thymidine was used as raw material to enzymatically synthesize other nucleosides, the production cost would be only about $1000/Kg.
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