An Efficient Chemoenzymatic Process for Preparation of Ribavirin

Ribavirin is an important antiviral drug, which is used for treatment of many diseases. The pilot-scale chemoenzymatic process for synthesis of the active pharmaceutical ingredient Ribavirin was developed with 32% overall yield and more than 99.5% purity. The described method includes the chemical synthesis of 1,2,4-triazole-3-carboxamide, which is a key intermediate and enzyme-catalyzed transglycosylation reaction for preparation of the desired product. 1,2,4-Triazole-3-carboxamide was synthesized from 5-amino-1,2,4-triazole-3-carboxylic acid by classical Chipen-Grinshtein method. Isolated from E. сoli BL21(DE3)/pERPUPHHO1 strain the purine nucleoside phosphorylase was used as a biocatalytical system. All steps of this process were optimized and scaled.

[1]  A. Memarnejadian,et al.  Co-expression of hepatitis C virus polytope–HBsAg and p19-silencing suppressor protein in tobacco leaves , 2016, Pharmaceutical biology.

[2]  P. Neubauer,et al.  Immobilization of thermostable nucleoside phosphorylases on MagReSyn® epoxide microspheres and their application for the synthesis of 2,6-dihalogenated purine nucleosides , 2015 .

[3]  P. Neubauer,et al.  Synthesis of 2,6-Dihalogenated Purine Nucleosides by Thermostable Nucleoside Phosphorylases , 2015 .

[4]  M. Lozano,et al.  Bioproduction of ribavirin by green microbial biotransformation , 2015, Process Biochemistry.

[5]  Xiukun Lin,et al.  Cytotoxicity of the compounds isolated from Pulsatilla chinensis saponins and apoptosis induced by 23-hydroxybetulinic acid , 2015, Pharmaceutical biology.

[6]  G. Massolini,et al.  Immobilized purine nucleoside phosphorylase from Aeromonas hydrophila as an on-line enzyme reactor for biocatalytic applications. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[7]  Chien-Jen Chen,et al.  Epidemiology and natural history of hepatitis C virus infection. , 2014, World journal of gastroenterology.

[8]  Yuechao Ma,et al.  Fermentative production of ribavirin by overexpressing purine nucleoside phosphorylase in Bacillus , 2014 .

[9]  A. Albertini,et al.  Developing a Collection of Immobilized Nucleoside Phosphorylases for the Preparation of Nucleoside Analogues: Enzymatic Synthesis of Arabinosyladenine and 2,3-Dideoxyinosine , 2013 .

[10]  I. Konstantinova,et al.  Chemoenzymatic method of 1,2,4-triazole nucleoside synthesis: Possibilities and limitations , 2013, Russian Journal of Bioorganic Chemistry.

[11]  J. J. Zhang,et al.  An Improved Procedure for the Preparation of Ribavirin , 2012 .

[12]  Zhinan Xu,et al.  Cloning and characterization of purine nucleoside phosphorylase in Escherichia coli and subsequent ribavirin biosynthesis using immobilized recombinant cells. , 2011, Enzyme and microbial technology.

[13]  A. Iribarren,et al.  Aeromonas hydrophila strains as biocatalysts for transglycosylation , 2010 .

[14]  D. Wei,et al.  Enzymatic synthesis of nucleosides by nucleoside phosphorylase co-expressed in Escherichia coli , 2010, Journal of Zhejiang University SCIENCE B.

[15]  L. Naesens,et al.  Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin , 2008, Bioorganic & Medicinal Chemistry.

[16]  N. Chen,et al.  Optimization of technical conditions of producing ribavirin byBacillus subtilis , 2009, Annals of Microbiology.

[17]  Jun-Ying Miao,et al.  Synthesis of novel ribavirin hydrazone derivatives and anti-proliferative activity against A549 lung cancer cells. , 2009, Carbohydrate research.

[18]  J. Montserrat,et al.  Chemoenzymatic preparation of nucleosides from furanoses , 2008 .

[19]  T. Araki,et al.  EFFICIENT CHEMO-ENZYMATIC SYNTHESES OF PHARMACEUTICALLY USEFUL UNNATURAL 2′-DEOXYNUCLEOSIDES , 2005, Nucleosides, nucleotides & nucleic acids.

[20]  I. Konstantinova,et al.  A New Effective Method for the Synthesis of 1,2,4-Triazole-3-carboxamide and Ribavirin Derivatives , 2005, Pharmaceutical Chemistry Journal.

[21]  J. Fernández‐Lucas,et al.  Nucleoside synthesis by immobilised bacterial whole cells , 2004 .

[22]  V. Barai,et al.  A Universal Biocatalyst for the Preparation of Base‐ and Sugar‐Modified Nucleosides via an Enzymatic Transglycosylation , 2002 .

[23]  A. Miroshnikov,et al.  Overexpression of Escherichia coli genes encoding nucleoside phosphorylases in the pET/Bl21(DE3) system yields active recombinant enzymes. , 2002, Protein expression and purification.

[24]  J. Arnold,et al.  The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen , 2000, Nature Medicine.

[25]  R. K. Robins,et al.  Design, synthesis, and broad spectrum antiviral activity of 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides , 1972 .

[26]  V. Y. Grinshtein,et al.  A new method of preparing 1, 2, 4-triazole carboxylic-3 acids , 1966 .