Preparation Of Nucleosides Research Articles

A practical synthesis of nucleoside 5′-diphosphates from nucleoside 5′-H-phosphonate monoesters

A simple and convenient synthetic protocols based on H-phosphonate chemistry have been developed for the preparation of nucleoside 5′-diphosphates. It consists of oxidation of the silylated H-phosphonate monoesters in pyridine with iodine to produce the corresponding N-pyridiniumphosphonate intermediates, followed by their reactions with orthophosphoric acid used as a nucleophile. The added value of the method is that substrates for the reaction, H-phosphonate monoesters, can be prepared in situ from the corresponding nucleosides and used for the next step without isolation. The procedure is simple and applicable to the preparation of various diphosphates of ribo- and deoxyribonucleosides, and their analogues.

New biocatalysts for one pot multistep enzymatic synthesis of pyrimidine nucleoside diphosphates from readily available reagents

Since the preparation of nucleoside 5′-diphosphates by classical methodologies is complex, multistep enzymatic systems were explored to synthesize pyrimidine nucleoside 5′-diphosphates starting from readily available reagents. Different strategies were combined to prepare uridine- and thymidine 5′-diphosphates as ribo- and deoxyribonucleoside models, respectively. For uridine 5′-diphosphate synthesis, conversions between 38 and 66% were achieved, using a simple methodology that involves commercial yeast extract as biocatalyst and biocatalytically in situ prepared uridine 5′-monophosphate. Corynebacterium ammoniagenes ATCC 19350 was used for the first time as biocatalyst to synthesize uridine 5′-monophosphate from uracil and orotic acid while Raoultella planticola was the selected biocatalyst for uridine 5′-monophosphate synthesis from uridine. The overall performances of all the tested approaches were similar but the use of uracil leads to a more suitable and cheaper process. Alternatively, for thymidine 5′-diphosphate synthesis two consecutive one pot multistep enzyme systems were assayed. In the first biotransformation, 2′-deoxyribose 5-phosphate was formed from glucose by Erwinia carotovora whole cells followed by the action of phosphopentomutase and thymidine phosphorylase affording thymidine in 85% conversion relative to 2′-deoxyribose 5-phosphate. Finally, in the second one pot reaction, the nucleoside was converted to thymidine 5′-diphosphate by the combined action of Escherichia coli BL21 pET22b-phoRp and Saccharomyces cerevisiae.

ChemInform Abstract: Target Cum Flexibility: Synthesis of C(3′)‐Spiroannulated Nucleosides.

AbstractA simple [2 + 2 + 2] cycloaddition protocol allows the preparation of nucleosides with modified sugar backbone for therapeutic use.

ChemInform Abstract: Preparation of Nucleoside 5′-Deoxy-5′-methylenephosphonates as Building Blocks for the Synthesis of Methylenephosphonate Analogues.

Efficient synthesis of suitably protected 2′-deoxycytidine, 2′-deoxyadenosine, and 2′-deoxyguanosine derivatives bearing the 5′-methylenephosphonate moiety with the 4-methoxy-1-oxido-2-picolyl function as an intramolecular nucleophile catalytic group is described.

Recent Approaches in the Synthesis of Conformationally Restricted Nucleoside Analogues

AbstractThis review describes some approaches in the synthesis of conformationally restricted nucleoside analogues. The focus is on the preparation of nucleosides as monomers modified only on the pentofurano sugar moiety, with an additional linkage capable of modulating the dynamic conformational equilibrium of natural nucleosides. The results of the different structural modifications in terms of pseudorotational analysis, as well as the potential use of such conformationally restricted nucleoside analogues, are briefly presented.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

RECOMBINANT BACTERIAL CELLS AS EFFICIENT BIOCATALYSTS FOR THE PRODUCTION OF NUCLEOSIDES

The preparation of nucleosides as well as their base-modified analogues using purified nucleoside phosphorylase enzymes or, more conveniently, using whole bacterial cells is described. The development of genetically modified strains of Escherichia coli, able to over-produce Uridine-phosphorylase and Purine-nucleoside-phosphorylase in the same cells, improves the specific biocatalytic activity and the consequent industrial scale approach.

Preparation of nucleoside 5′-deoxy-5′-methylenephosphonates as building blocks for the synthesis of methylenephosphonate analogues

Efficient synthesis of suitably protected 2′-deoxycytidine, 2′-deoxyadenosine, and 2′-deoxyguanosine derivatives bearing the 5′-methylenephosphonate moiety with the 4-methoxy-1-oxido-2-picolyl function as an intramolecular nucleophile catalytic group is described.

ChemInform Abstract: Use of Ammonium Aryl H‐Phosphonates in the Preparation of Nucleoside H‐ Phosphonate Building Blocks.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Preparation of fluorinated galactosyl nucleoside diphosphates to study the mechanism of the enzyme galactopyranose mutase

A novel latent→active phosphorylation strategy has been employed for the preparation of two fluorinated nucleoside diphosphates (compounds I and II). The strategy is based on the isomerisation of substituted allyl to vinyl glycosides which were subsequently phosphorylated by treatment with dibenzyl hydrogen phosphate, N-iodosuccinimide and a catalytic amount of trimethylsilyl triflate. This methodology is very suitable for the preparation of nucleoside diphosphates that have a modification in the saccharide moiety since the allyl moiety serves first as an anomeric protecting group, allowing for protecting-group manipulation and functionalisation of the sugar ring, but after isomerisation to the corresponding vinyl glycoside it acts as an anomeric leaving group. The 2-F and 4-F Gal-UDP derivatives I and II do not inhibit the enzyme galactopyranose mutase in the direction pyranose → furanose but both compounds have been found to inhibit the reverse reaction.

Recent advances in the chemistry of nucleosides and their analogs (review)

Methods for the preparation of nucleosides and their analogs, C-nucleosides, and cyclonucleosides, and their properties are reviewed.

The preparation of nucleosides from 3-deoxy-3- C-( R)-ethoxycarbonyl(formylamino)methyl-1,2:5,6-di- O-isopropylidene-α- D-allofuranose

The preparation of nucleosides from 3-deoxy-3- C-( R)-ethoxycarbonyl(formylamino)methyl-1,2:5,6-di- O-isopropylidene-α- D-allofuranose

Attempted preparation of nucleoside and deoxynucleoside 3′,5′-cyclic carbonates

Attempted preparation of nucleoside and deoxynucleoside 3′,5′-cyclic carbonates

Preparation of nucleosides via isopropylidene sugar derivatives : Part VI. Synthesis of 9-α- and 9-β- d-allofuranosyladenines

2,3:5-6-Di- O-isopropylidene- d-allono-1,4-lactone was reduced with bis(2-butyl-3-methyl)borane to 2,3:5,6-di- O-isopropylidene- d-allofuranose. Reaction with thionyl chloride gave the halogenose, which was condensed with 6-benzamido-chloromercuripurine. Both the α- and β-anomers resulted. Several crystalline derivatives were isolated during the stepwise removal of the blocking groups to yield 9-α-and 9-β- d-allofuranosyladenine. The anomeric configurations were established by degradation of 9-(2,3- O-isopropylidene-β- d-allofuranosyl)adenine to 9-(2,3- O-isopropylidene-β- d-ribofuranosyl)adenine, and degradation of 9-(2,3- O-isopropylidene-α- d-allofuranosyl)adenine to 9-α- d-ribofuranosyladenine.

Preparation of nucleosides via isoropylidene sugar derivatives : Part V. Coupling reactions using the titanium tetrachloride method

Sugar derivatives that are blocked with isopropylidene groups can be converted directly to adenine nucleosides, if they are first acylated and then coupled with 6-benzamidochloromercuripurine by the titanium tetrachloride procedure. The preparation of 9-(2-3- O-isopropylidene-α- L-rhamnofuranosyl)adenine, 9-α- L-rhamnofuranosyladenine, 9-(2,3- O-isopropylidene-α- D-mannofuranosyl)adenine, 9-α- D-mannofuranosyladenine, and 9-β- D-mannofuranosyladine are described. 9-β- D-Mannofuranosyladenine was also produced in extremely small yield by treatment of 2,3:5,6-di- O-isopropylidene-α- D-mannofuranosyl chloride with 6-benzamidochloromercuripurine in xylene at reflux.

Preparation of nucleosides via isopropylidene sugar derivatives. IV. Synthesis of 9-alpha and 9-beta-L-erythrofuranosyladenine.

Preparation of nucleosides via isopropylidene sugar derivatives. IV. Synthesis of 9-alpha and 9-beta-L-erythrofuranosyladenine.

A preparation of nucleosides by the hydrolysis of 5'-nucleotides

A preparation of nucleosides by the hydrolysis of 5'-nucleotides

核酸の抽出及び水解によるヌクレオシドの単離

A process whereby nucleosides are prepared in a good yield from yeast nucleic acid, as the starting material for the synthesis of nucleotide, coenzymes and their allied compounds, was devised. Extraction of ribonucleic acid (RNA) was made through improvement of the Clarke-Schryver method and 50-60g. of RNA was obtained for 1kg. of dry yeast. Cytosine was abnormally small in this RNA. RNA was also obtained from the baker's yeast, torula yeast, and medicinal yeast, as well as from the brewer's yeast. Preparation of nucleoside by hydrolysis of RNA was examined and following procedure was adopted. After hydrolysis with 50% pyridine, guanosine was removed, a majority of adenosine was removed from ethanolic solution, and the solution was divided into uridine and cytidine-adenosine portions by ion exchanger, Amberlite IR-120. Cytidine and adenosine were separated by sulfate fractionation and cellulose-powder-chromatography. Shortening of the hydrolysis period to one half was effected by preliminary hydrolysis with N sodium hydroxide to nucleotide and then hydrolyzed with pyridine.