- Development of a nanostabilized biocatalyst using an extremophilic microorganism for ribavirin biosynthesis
-
Ribavirin is a guanosine analogue commonly used as an antiviral compound for the treatment of Hepatitis C virus (HCV) infection. The biosynthesis of this compound using Geobacillus kaustophilus ATCC 8005 as biocatalyst is herein reported. This extremophilic microorganism has been successfully entrapped in an agarose matrix supplemented with bentonite, which was defined as bionanocomposite. This immobilized biocatalyst was stable for more than 580 h without activity loss, significantly improving operational stability and mechanical properties over the conventional agarose matrix. Furthermore, a packed-bed bioreactor for bioprocess scale-up was designed, which was able to produce 370 mg L-1 of ribavirin. In conclusion, a smooth, inexpensive and environmentally friendly method to obtain ribavirin was developed in this study.
- De Benedetti, Eliana C.,Rivero, Cintia W.,Trelles, Jorge A.
-
-
Read Online
- Ribavirin: Biotechnological synthesis and effect on the reproduction of Vaccinia virus
-
The biotechnological method of synthesis of ribavirin, vidarabin, and 6-azauridine by the use of immobilized recombinant enzymatic preparations of nucleoside phosphorylase was improved. The effect of ribavirin and its combinations with the other synthesized nucleosides on the reproduction of Vaccinia virus was studied on the culture of Vero cells. The combination of ribavirin and vidarabin was shown to provide the antiviral effect at lesser concentrations than with these compounds taken separately.
- Konstantinova,Leont'eva,Galegov,Ryzhova,Chuvikovskii,Antonov,Esipov,Taran,Verevkina,Feofanov,Miroshnikov
-
-
Read Online
- Purification and properties of purine nucleoside phosphorylase from Brevibacterium acetylicum ATCC 954.
-
Purine nucleoside phosphorylase of Brevibacterium acetylicum ATCC 954, which catalyzes the production of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a potent antiviral agent, from purine nucleoside and 1,2,4-triazole-3-carboxamide in a high yield, was purified 49-fold. This enzyme had a molecular weight of 31,000 and was a monomer. The isoelectric point of the enzyme was 4.7. The optimal temperature and pH of inosine phosphorolyzing reaction catalyzed by the enzyme was around 8.5 and 70 degrees C, respectively. The Michaelis constants for inosine, guanosine, and ribavirin were 1.43 mM, 2.44 mM and 2.08 mM, respectively, at 40 degrees C. This enzyme appeared to be a SH enzyme because it was inactivated by SH reagents, p-chloromercuribenzoate and N-ethylmaleimide, and HgCl2. In addition, this enzyme was completely inactivated by AgNO3 and was slightly inhibited by CuSO4. It showed nucleoside-phosphorolyzing activity toward inosine, 2'-deoxyinosine, 2',3'-dideoxyinosine, guanosine, 2'-deoxyguanosine, and xanthosine. However, adenosine and its derivatives could not be phosphorolyzed. This enzyme could not also phosphorolyze various 5'-mononucleotides. According to the amino terminal sequence analysis, the twenty residues from the amino terminal end of this enzyme were identified as follows: MTVNWNETRS-FLECKMQAKPE.
- Shirae,Yokozeki
-
-
Read Online
- Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: Adenosine deaminase catalyzes two consecutive deamination reactions
-
Ribavirin is an approved broad-spectrum antiviral drug. A liver-targeting prodrug of ribavirin, viramidine, is in clinical trial in an attempt to provide a better therapeutic index. The conversion of viramidine to ribavirin, and of ribavirin to an inactive metabolite through adenosine deaminase, is reported. Kinetic analysis indicates that adenosine deaminase is likely involved in activation of viramidine in vivo, and the process is highly pH sensitive. The differential activities of two consecutive deamination reactions are kinetically studied and interpreted based on adenosine deaminase structural information. A comprehensive understanding of the viramidine and ribavirin deamination mechanism should help in designing better nucleoside therapeutics in the future.
- Wu, Jim Zhen,Walker, Heli,Lau, Johnson Y. N.,Hong, Zhi
-
-
Read Online
- A universal biocatalyst for the preparation of base- and sugar-modified nucleosides via an enzymatic transglycosylation
-
The E. coli BMT-4D/1A cells have been selected according to Munch-Petersen et al. They carry two regulatory mutations (cytR and deoR) and are able to synthesize constitutively nucleoside-catabolizing enzymes, e.g., cells that possess high UPase and PNPase activities. The cells have been cross-linked by glutaraldehyde to afford a biocatalyst that retained high UPase and PNPase activities and was comfortable for repeated use. An incubation of 2′-deoxyguanosine (1) and 2-chloroadenine (2) (molar ratio 3:1) in K-phosphate buffer (10 mM; pH 7.0) in the presence of the biocatalyst at 65° for 7 h resulted in quantitative transformation of 2 into 2-chloro-2′-deoxyadenosine (4; cladribine) that was isolated in 81% yield (Scheme 1). Similarly, the reaction of guanosine (5) and 1,2,4-triazole-3-carboxamide (6) (molar ratio 1:1) in K-phosphate buffer (10mM; pH 7.0) in the presence of the biocatalyst at 60° for 30h led to the formation of 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (8; ribavirin) in 90-92% yield (67-70% isolated yield) (Scheme 2).
- Barai, Vladimir N.,Zinchenko, Anatoli I.,Eroshevskaya, Ludmilla A.,Kalinichenko, Elena N.,Kulak, Tamara I.,Mikhailopulo, Igor A.
-
-
Read Online
- Method for preparing ribavirin by one-pot method
-
The invention belongs to the technical field of chemical synthesis, and relates to a method for preparing ribavirin by a one-pot method. The method comprises the following steps: heating and keeping warm to carry out a reaction on tetraacetyl ribose, methyl 1,2,4-triazole-3-carboxylate and bis(p-nitrophenyl)phosphate under the vacuum degree of-0.09 MPa; cooling a product after the heat preservation reaction is finished, adding a saturated methanol-ammonia solution, and reacting at normal temperature; and concentrating reaction liquid obtained after the normal-temperature reaction is finished,adding 90% ethanol, recrystallizing, centrifugally filtering, and drying to obtain a ribavirin product. According to the method, condensation, ammonolysis and refining are carried out in a reaction container in a one-pot reaction mode, intermediate separation and refining are not needed in the process, operation steps are reduced, the yield of the final product ribavirin can be increased, and theyield of the ribavirin synthesis method provided by the invention can reach 70%-80%.
- -
-
Paragraph 0044-0057
(2020/09/20)
-
- A 1/10 water ribavirin compounds and pharmaceutical compositions thereof (by machine translation)
-
The invention discloses a 1/10 water ribavirin compounds and pharmaceutical compositions thereof, per mole of ribavirin compounds containing 1/10 mole water. Its infrared spectrum in the wave number is 3451.8 ± 2 cm- 1 , 3347.5 ± 2 cm- 1 , 2857.1 ± 2 cm- 1 , 1663.3 ± 2 cm- 1 , 1502.8 ± 2 cm- 1 , 1438.4 ± 2 cm- 1 , 1336.8 ± 2 cm- 1 , 1281.8 ± 2 cm- 1 , 1070.3 ± 2 cm- 1 , 892.8 ± 2 cm- 1 , 773.3 ± 2 cm- 1 , 672.0 ± 2 cm- 1 There is a characteristic absorption peak. The invention through crystallization of the ribavirin impact factors study and research of different crystallization solvent system, to prepare high purity, good stability 1/10 water RBV compound, and by this invention stated 1/10 water RBV compound preparation has good stability of the pharmaceutical composition. (by machine translation)
- -
-
-
- Ribavirin preparation method
-
The invention provides a Ribavirin preparation method and belongs to the technical field of pharmaceutical synthesis. The method comprises following steps: tetraacetylribose and methyl triazole carboxylate are subjected to a condensation reaction under catalysis of iodine firstly, a Ribavirin intermediate is obtained and subjected to an ammonolysis reaction, and Ribavirin is obtained. Yield and purity of the Ribavirin intermediate obtained with the method are higher, the yield of the Ribavirin intermediate is 80%-82%, and the purity is 98.5%-98.7%; total yield and purity of the finally prepared Ribavirin are higher, the total yield is 77.6%-79.5%, and the purity is 98.5%.
- -
-
Paragraph 0038; 0040; 0044; 0046; 0047; 0049; 0050; 0052
(2019/02/27)
-
- Ribavirin compound containing one-twentieth water
-
The invention discloses a ribavirin compound containing one-twentieth water. Each mole of the ribavirin compound contains one-twentieth mole of water. After a crude ribavirin product is dissolved in water, the temperature and pH of a solution are controlled, and crystallization is carried out in an acetonitrile aqueous solvent to obtain the ribavirin compound containing one-twentieth water. The prepared product has high purity and stability and a higher application value.
- -
-
Paragraph 0047; 0052; 0053
(2019/01/23)
-
- The use of a four-acetyl ribose nucleoside cracking after crystallization of the raffinate and method
-
The invention discloses a method for using tetraacetylribose crystallization residual liquor after splitting decomposition of nucleoside. The tetraacetylribose crystallization residual liquor after splitting decomposition of nucleoside is residual crystallization mother liquor after preparation of 1,2,3,5-tetra-O-acetyl-beta-D-furan ribose through catalytic acylation splitting decomposition and recrystallization of nucleoside, wherein the mother liquor contains 1,2,3,5-tetra-O-acetyl-alpha-D-furan ribose. The method comprises the following steps: extracting the tetraacetylribose crystallization residual liquor after splitting decomposition of nucleoside by using an extraction solution to obtain 1,2,3,5-tetra-O-acetyl-alpha-D-furan ribose; then carrying out condensation reaction with 1,2,4-triazole-3-carboxylic acid methyl ester under the action of a catalyst to prepare a ribavirin condensation compound 1-(2,3,5-tri-O-acetyl-beta-D-furanribosyl)-1H-1,2,4-3-carboxylic acid methyl ester; and carrying out ammonolysis on the ribavirin condensation compound to obtain ribavirin. The method disclosed by the invention turns waste into wealth and treats and converts tetraacetylribose crystallization mother liquor produced in an existing process, so that the discharge of waste liquor in a production process of tetraacetylribose is reduced.
- -
-
-
- Preparation of L-ribavirin (by machine translation)
-
The invention provides a method for the preparation of ribavirin, to inosine as raw materials, after acetylation, condensation, aminolysis step to obtain the target product, the alkali in the acylation reaction of aluminum trichloride as a catalyst is conducted under the condition of, said condensation is in the NaI is conducted under the conditions of the catalyst, the aminolysis in methanol of existence of the sodium is conducted under the condition of. The method improves the acetylation efficiency, improves the yield of target product purity, shortens the reaction time, more easy to operate, is very suitable for industrial application. (by machine translation)
- -
-
Paragraph 0021; 0024; 0028
(2018/04/03)
-
- Chemical synthetic method for ribavirin condensation compound
-
The invention discloses a chemical synthetic method for a ribavirin condensation compound. The method comprises the following specific steps: S1, adding 1-trimethyl silane-1H-1,2,4-trizole-3-formamide, hexamethyldisilazane and ammonium sulfate into a 500ml three-necked bottle; S2, carrying out drying by distillation at a reduced pressure to obtain a yellow oily substance; S3, pouring a reaction liquid into ice water of sodium hydrogen carbonate after reaction detected by thin plate column chromatography; S4, dissolving the product prepared in the S3 in an ammonia saturated solution of methanol; S5, then adding ethanol and fully stirring and filtering the mixture; and S6, dissolving the combined filter cake in a heating condition in ethanol, decoloring the mixture through a decoloring agent, and filtering and cooling and crystallizing the mixture to obtain white crystal powder. According to the improved process, raw materials are easily available, the reaction condition is mild, the intermediates are not separated and purified, the method is simple to operate, the total yield can reach 65% or above, and the purity of prepared ribavirin is 99% or above.
- -
-
Paragraph 0020-0043
(2018/09/21)
-
- A RBV aminolysis reaction abolishes solvent method (by machine translation)
-
This invention involves a kind of RBV aminolysis reaction abolishes solvent virulences method, the method is to RBV intermediate reaction the liquid ammonia ribavirin condensation compound, extremely high purity by crude ribavirin. The process of the invention eliminate the toxicity solvent methanol, without long-term open ammonia, nor need concentrated methanol, reaction time is short, simple and convenient operation, liquid ammonia can be applied repeatedly, energy-saving and emission reduction, environmental protection, the product purity, high yield, low cost, it is more suitable for large scale industrial production, and the like, has obvious implementation value and social, economic benefits. (by machine translation)
- -
-
Paragraph 0022; 0023; 0024
(2016/10/24)
-
- Design and synthesis of HCV agents with sequential triple inhibitory potentials
-
The union of HCV-796, a potent selective HCV NS5B polymerase inhibitor, and Ribavirin, a molecule with activities against a wide spectrum of viruses, resulted in a class of new anti-HCV agents with a sequential triple inhibitory mechanism.
- Zhu, Tianmin,Fawzi, Mahdi B.,Flint, Michael,Kong, Fangming,Szeliga, Jan,Tsao, Russ,Howe, Anita Y.M.,Pan, Weitao
-
supporting information; experimental part
p. 5212 - 5216
(2010/10/03)
-
- Aeromonas hydrophila strains as biocatalysts for transglycosylation
-
Microbial transglycosylation is useful as a green alternative in the preparation of purine nucleosides and analogues, especially for those that display pharmacological activities. In a search for new transglycosylation biocatalysts, two Aeromonas hydrophila strains were selected. The substrate specificity of both micro-organisms was studied and, as a result, several nucleoside analogues have been prepared. Among them, ribavirin, a broad spectrum antiviral, and the well-known anti HIV didanosine, were prepared, in 77 and 62% yield using A. hydrophila CECT 4226 and A. hydrophila CECT 4221, respectively. In order to scale-up the processes, the reaction conditions, product purification and biocatalyst preparation were analyzed and optimized.
- Nbile, Matas,Terreni, Marco,Lewkowicz, Elizabeth,Iribarren, Adolfo M.
-
experimental part
p. 395 - 402
(2011/10/08)
-
- Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin
-
Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to investigate the lack of enhancement of potency by the ProTides, and these indicate a failure at the final, amino acid cleavage step in the ProTide activation process, leading to inefficient release of the nucleoside monophosphate.
- Derudas, Marco,Brancale, Andrea,Naesens, Lieve,Neyts, Johan,Balzarini, Jan,McGuigan, Christopher
-
body text
p. 2748 - 2755
(2010/06/19)
-
- Synthesis of novel ribavirin hydrazone derivatives and anti-proliferative activity against A549 lung cancer cells
-
A series of novel ribavirin hydrazone derivatives were synthesized by the reaction of ribavirin hydrazone with benzaldehyde or acetophenone derivatives. The structures of the compounds were determined by IR, 1H NMR, and HRESIMS. Preliminary bio
- Liu, Wei-Yong,Li, Hai-Ying,Zhao, Bao-Xiang,Shin, Dong-Soo,Lian, Song,Miao, Jun-Ying
-
experimental part
p. 1270 - 1275
(2009/10/26)
-
- Chemoenzymatic preparation of nucleosides from furanoses
-
Chemoenzymatic preparation of ribose, deoxyribose and arabinose 5-phosphates was accomplished. These compounds were tested as starting materials in the enzymatic preparation of natural and modified purine and pyrimidine nucleosides, using an overexpressed Escherichia coli phosphopentomutase.
- Taverna-Porro, Marisa,Bouvier, Leon A.,Pereira, Claudio A.,Montserrat, Javier M.,Iribarren, Adolfo M.
-
p. 2642 - 2645
(2008/09/19)
-
- High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
-
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
- Bookser, Brett C.,Raffaele, Nicholas B.
-
p. 173 - 179
(2007/10/03)
-
- Synthesis and biological evaluation of novel apio nucleosides with thiazole-4-carboxamide and 1,2,4-triazole-3-carboxamide
-
In view of biological activities of azole nucleosides and apio-dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3-O-isopropylidene-apio-β -D-furanose (3), which was prepared from D-mannose.
- Kim, Myong Jung,Jeong, Lak Shin,Kim, Joong Hyup,Shin, Ji Hye,Chung, Soon Yong,Lee, Sang Kook,Chun, Moon Woo
-
p. 715 - 724
(2007/10/03)
-
- Specificity in treatment of diseases
-
A drug is modified by covalently coupling a blocking group to the drug via a nitrogen atom in the blocking group. The blocking group in the modified drug prevents metabolic conversion and sequestration of the drug in non-target cells, and the blocking group is enzymatically removed in the target cell. Particularly contemplated advantages of presented compounds and methods include reduction of cytotoxicity by inhibition of metabolic conversion to potentially cytotoxic metabolites, reduction of dosages of drugs by reduction of sequestration into non-target cells, and increase of selectivity of a drug.
- -
-
-
- Treatment of viral infections using the L-isomer of ribavirin
-
A 1-(β-L-ribofuranosyl)-1,2,4-triazole-3-carboxamide is administered in a method of treatment of a viral infection in a patient, including HIV infection, HCV infection, or BHV infection.
- -
-
-
- Purine nucleoside synthesis from uridine using immobilised Enterobacter gergoviae CECT 875 whole cells
-
Biocatalysed purine nucleoside synthesis was carried out using immobilised Enterobacter gergoviae CECT 875. Similar yields (80-95%) in adenosine were obtained with both free and immobilised cells though in the last case a long reaction time was necessary. The immobilised cells can be reused at least for more than 30 times without significant loss of enzymatic activity. The immobilised biocatalyst in agarose is active in the synthesis of unnatural nucleosides.
- Trelles,Fernández,Lewkowicz,Iribarren,Sinisterra
-
p. 2605 - 2609
(2007/10/03)
-
- Process for the preparation of ribavirin
-
A process for the preparation of ribavirin on an industrial scale is described which comprises the reaction of glycosylation of 3-substituted triazoles in the presence of a Lewis acid. Said process comprises:a) the reaction of a triazole of the formula with a protected ribofuranose of the formulab) the removal of the Pg groups and, optionally, the conversion into a carhoxyamide group of the R2 group of the compound obtained of the formula
- -
-
-
- Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
-
The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (""RT-PCR""). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
- -
-
-
- Carbohydrate conjugated bio-active compounds
-
Methods and compositions are provided which increase the cellular uptake of bioactive materials by covalently bonding such compounds to carbohydrate moieties through chemical linkers using other than glycosidic bonds. Numerous carbohydrates, linkers and bioactive materials can be joined in this way to form novel compositions, which are collectively referred to herein as glinkosides. Preferred glinkosides are preferentially taken up by glucose receptor and/or other cellular receptors, and once inside the cells, the glinkosides are cleaved into a sugar, a linker or linker fragments, and a biologically active compound. Various aspects of the invention include processes for synthesizing glinkosides, glinkoside compositions, and methods of treating diseases using glinkosides.
- -
-
-
- Synthesis and Antiviral Evaluation of N-Carboxamidine-Substituted Analogues of 1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamidine Hydrochloride
-
Ten, hitherto unreported, analogues of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (2a, ribamidine) and methyl carboxamidate 5 have been synthesized.These include the N-cyano (2b), N-alkyl (2c-e), N-amino acid (2f-h), N,N'-disubstituted (6,7a,b), and the N-methylated carboxamide (1f) analogues of ribavirin.In addition, a new facile synthesis of carboxamidine 2a was also developed.All compounds were evaluated for biological activity against the following RNA viruses: Punta Toro (PT) and sandfly fever (SF) viruses (bunyaviruses); Japanese encephalitis (JE), yellow fever (YF), and dengue-4 viruses (flaviviruses); parainfluenza type 3 (PIV3), respiratory syncytial virus (RSV), and measles viruses (paramyxoviruses); influenza A and B viruses (orthomyxoviruses); Venezuelan equine encephalomyelitis virus (VEE, alphavirus); human immunodeficiency virus type-1 (HIV-1, lentivirus); the DNA-containing vaccina (VV) virus (poxvirus); and adeno type-5 (Ad5) viruses.All of the compounds except for 2a and 7a,b exhibited activity against the bunyaviruses such as that observed with 2a; however, higher IC50 values were generally observed.Glycine analogue 2f showed activity in PT-virus-infected mice in therms of increased survivors and descreased markers of viral pathogenicity.Carboxamidine 2a, carboximidate 5, and dimethyl amidine 6 exhibited activity against dengue type-4 virus.Monomethyl amidine 2c demonstrated activity against RSV, PIV3, and, to a lesser extent, influenza A and B.Activity of 2c generally required higher IC50 values than unsubstituted 2a.The latter exhibited hitherto unreported activity against RSV; therapeutic indices for 2a against RSV and PIV3 were >64 and >21.No substantial in vitro activity was observed for any of the compounds tested against Ad5, measles, JE, YF, VEE, or HIV-1.In addition, evidence is presented which argues in favor of a distinct antiviral mechanism of action for carboxamidines, e.g. 6, in contrast to a role as a carboxamide precursor.
- Gabrielsen, Bjarne,Phelan, Michael J.,Barthel-Rosa, Luis,See, Cathy,Huggins, John W.,et al.
-
p. 3231 - 3238
(2007/10/02)
-
- ENZYMATIC PREPARATIONS AND REGIOCHEMICAL PROPERTIES OF SOME NEW ADP-RIBOSYLATED 1,2,4-TRIAZOLES
-
NAD nucleosidase-catalysed trans-ADP-ribosylation has been investigated for some 1,2,4-triazole bases.The unsubstituted base 1 provided N4-ribosylated triazoles (14 and 9), whereas 3-substituted (amino, chloro, mercapto, and carbamoyl)triazoles 2-4 and 6 underwent a regiospecific N1-ribosylation to produce the corresponding triazole adenine dinucleotides 10-13 in a good or moderate yield.Dinucleotide structures and the site of ribosylation were verified by 1H and 15N NMR spectrometries.The 3-carbamoyltriazole dinucleotide 13 can be a useful intermediate on the road to the antiviral agent, ribavirin, 18.
- Tono-oka, Shuichi,Azuma, Ichiro
-
p. 297 - 300
(2007/10/02)
-
- Enzymatic Production of Ribavirin from Orotidine by Erwinia carotovora AJ 2992
-
Microorganisms that produce ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; virazoleR) directly from orotidine and 1,2,4-triazole-3-carboxamide (TCA) were screened from our stock cultures.Of the 425 strains, Erwinia carotovora AJ 2992 was found to possess potent ribavirin-producing ability, from orotidine and TCA.In the presence of intact cells of E. carotovora AJ 2992, 183 mM ribavirin was produced from 300 mM orotidine and 300 mM TCA on 48 hr reaction.
- Shirae, Hideyuki,Yokozeki, Kenzo,Kubota, Koji
-
p. 1499 - 1504
(2007/10/02)
-
- Enzymatic Synthesis of Virazole by Purine Nucleoside Phosphorylase of Enterobacter aerogenes
-
A potent antiviral agent, Virazole (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), was synthesized from inosine and 1,2,4-triazole-3-carboxamide (TCA) by a two step reaction with purified purine nucleoside phosphorylase (PNPase) of Enterobacter aerogenes AJ 11125.The first step involves the production of ribose-1-phosphate (R-1-P) through the phosphorolysis of inosine.The second step involves the production of Virazole through the transribosyl reaction of R-1-P and TCA.The R-1-P produced from inosine was isolated by ion-exchange chromatography and used as a substrate for Virazole synthesys without crystallization.TCA (10 mM) was transformed to Virazole with a 75percent yield (molar basis) in the presence of 50 mM R-1-P.Enzymatically synthesized Virazole was isolated from a large scale reaction mixture and identified by physicochemical means.The Km values of PNPase for TCA and hypoxanthine were 167 mM and 5.6 mM, respectively.
- Utagawa, Takashi,Morisawa, Hirokazu,Yamanaka, Shigeru,Yamazaki, Akihiro,Hirose, Yoshio
-
p. 121 - 126
(2007/10/02)
-
- Nucleoside Syntheses, XXII. Nucleoside Synthesis with Trimethylsilyl Triflate and Perchlorate as Catalysts
-
The novel Lewis acids (CH3)3SiOSO2CF3 (5), (CH3)3SiOSO2C4F9 (6), and (CH3)3SiClO4 (4) are highly selective and efficient Friedel-Crafts catalysts for nucleoside formation from silylated heterocycles and peracylated sugars as well as for rearrangements of persilylated protected nucleosides.With basic silylated heterocycles these new catalysts give much higher yields of the natural N-1-nucleosides than with SnCl4.
- Vorbrueggen, Helmut,Krolikiewicz, Konrad,Bennua, Baerbel
-
p. 1234 - 1255
(2007/10/02)
-
- Process for preparing 1,2,4-triazole nucleosides
-
1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide is prepared by a process wherein a suitably substituted formimidic acid hydrazide is condensed with a blocked derivative of D-ribose and the intermediate is ring closed with a reagent which donates one carbon atom to yield a 3-substituted-1-(blocked β-D-ribofuranosyl)-1,2,4-triazole. Treatment of this intermediate with ammonia and/or removal of the blocking group yields the product.
- -
-
-
- 1,2,4-Triazole nucleosides
-
As antiviral agents and intermediates therefor, 3-substituted 1-(β-D-glycosyl)-1,2,4-triazoles, O-acylated analogs thereof, and 5'- and 3',5'-cyclic phosphates of the triazole nucleosides, "glycosyl" being .[.a pentofuranosyl moiety, preferably one whose 2'-oxygen is trans to the triazole aglycon, e.g., xylofuranosyl,.]. ribofuranosyl, .[.2-0-methylribofuranosyl, etc.,.]. the triazole aglycon being 3-substituted with cyano, methylcarboxylate, carboxamidoxime, carboxamido-, thiocarboxamido, or carboxamidine. Preparation of these nucleosides is by silylation of the substituted triazole followed by glycosylation with the appropriate blocked glycosyl halide. Alternatively, acid-catalyzed fusion of the requisite 1,2,4-triazole with an O-acylated pentofuranose yields the nucleosides.
- -
-
-
