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A kind of synthetic method of β-thymidine

A synthesis method and technology for thymidine, applied in the field of synthesis of β-thymidine, can solve the problems of high cost of treatment of fermentation broth wastewater, difficult treatment of bromine and nickel waste, multi-industrial waste products, etc. Chemical reaction steps, the effect of reducing industrial waste

Active Publication Date: 2019-09-24
SUZHOU DUMEI BIOTECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The cost of this chemical synthesis method is relatively high, and more industrial waste products will be produced, and the bromine and nickel wastes in the waste products are difficult to handle
[0008] In addition to chemical synthesis, it can also be produced by yeast fermentation. Although the cost of raw and auxiliary materials for the production of β-thymidine by fermentation has dropped a lot, it must be produced continuously in large quantities, and the cost of wastewater treatment of the fermentation liquid is also high.

Method used

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  • A kind of synthetic method of β-thymidine
  • A kind of synthetic method of β-thymidine
  • A kind of synthetic method of β-thymidine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Add 1eq 5-methyluridine, 0.1eq adenosine triphosphate (ATP), 0.1eq NADPH, enzyme concentration flavin adenine dinucleotide (FAD), enzyme concentration MgSO 4 , glucose dehydrogenase, uridine kinase, sepitate kinase, ribonucleoside diphosphate reductase, thymidylate kinase and thymidine kinase in phosphate buffer containing 10 mM NaCl, using HCl and NaOH to maintain pH The value is 6, the reaction temperature is 20°C, and the reaction time is 20h.

[0035] Compared with the common chemical synthesis method, the waste water generated in the reaction process is reduced by 33%.

Embodiment 2

[0037] Add 1eq 5-methyluridine, 0.1eq adenosine triphosphate (ATP), 0.1eq NADPH, enzyme concentration flavin adenine dinucleotide (FAD), enzyme concentration MgSO 4 , glucose dehydrogenase, uridine kinase, sepitate kinase, ribonucleoside diphosphate reductase, thymidylate kinase and thymidine kinase in phosphate buffer containing 10 mM NaCl, using HCl and NaOH to maintain pH The value is 7, the reaction temperature is 45°C, and the reaction time is 30h.

[0038] Compared with the common chemical synthesis method, the waste water generated in the reaction process is reduced by 31%.

Embodiment 3

[0040] Add 1eq 5-methyluridine, 0.1eq adenosine triphosphate (ATP), 0.1eq NADPH, enzyme concentration flavin adenine dinucleotide (FAD), enzyme concentration MgSO 4 , glucose dehydrogenase, uridine kinase, sepitate kinase, ribonucleoside diphosphate reductase, thymidylate kinase and thymidine kinase in phosphate buffer containing 10 mM NaCl, using HCl and NaOH to maintain pH The value is 8, the reaction temperature is 30°C, and the reaction time is 37h.

[0041] Compared with the common chemical synthesis method, the waste water generated in the reaction process is reduced by 38%.

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Abstract

Disclosed in the preset invention is a method for use in synthesizing β-thymidine: enzyme engineering is used to reverse-synthesize thymidine; glucose dehydrogenase, uridine kinase, squid acid kinase, ribonucleoside diphosphate reductase, thymidylate kinase and thymidine kinase are used, while 5-methyluridine is used as a raw material and undergoes two steps of phosphorylation to generate nucleotides, which are then converted into deoxynucleotides, two steps of dephosphorylation being carried out to generate thymidine.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of β-thymidine. Background technique [0002] β-Thymidine (β-Thymidine) plays an important role in the production of antiviral drugs and biomedical applications. β-Thymidine is a synthetic anti-AIDS drug (AIDS) Zidovudine (Zidovudine) The main raw material of (Stavudine), no natural product exists, and its structure is as shown in the following formula: [0003] [0004] At present, the synthesis method of β-thymidine mainly adopts chemical synthesis method, which is obtained through bromination reaction, reduction reaction and saponification reaction. The synthesis process is as follows: [0005] [0006] [0007] The cost of this chemical synthesis method is relatively high, and more industrial waste products will be produced, and the bromine and nickel wastes in the waste products are difficult to handle. [0008] In addition to chemica...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/38
Inventor 陈车翘
Owner SUZHOU DUMEI BIOTECH CO LTD
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