Reaction Of Uridine Research Articles

Palladium-Catalyzed C-H Olefination for Nucleic Acid Production.

The palladium-catalyzed direct C-H olefination of unprotected uridine, 2'-deoxyuridine, uridine monophosphate, and uridine analogues are described here. This protocol provides an efficient, atom-economical, and environmentally friendly method for the introduction of an alkenyl group at the C5 position of the uracil without pre-functionalization. A series of C5-alkenylated uridine analogues, including some biologically significant compounds and potential pharmaceutical candidates, were synthesized with exposed hydroxyl groups on the ribose. © 2023 Wiley Periodicals LLC. Basic Protocol 1: The reaction of uridine, 2'-deoxyuridine, and sofosbuvir for the C-H olefination with methyl acrylate Basic Protocol 2: The reaction of uridine and 2'-deoxyuridine for the C-H olefination with styrene.

Photohydrate‐Mediated Reactions of Uridine, 2′‐Deoxyuridine and 2′‐Deoxycytidine with Amines at Near Neutral pH

Photohydrates are formed in high yield when uridine (Urd), 2'-deoxyuridine (dUrd), cytidine (Cyd) and 2'-deoxycytidine (dCyd) are irradiated with UVC in aqueous solution. The thermal reactions of the photohydrates of Urd with amines at pH values near pH 7.5 have been studied using UV spectroscopy, HPLC, mass spectrometry and, in some cases, NMR. It has been found that a number of amines (i.e. ethylenediamine, N,N'-dimethylethylenediamine, glycine, glycinamide, glycylglycine, glycylgylcylglycine, putrescine, spermidine and spermine) react thermally with such hydrates to form products with UV spectra characteristic of opened ring uridine-amine adducts. In general, these products display a strong absorption peak with λmax in the range between 288 and 310 nm. Mass spectral studies of a number of the products indicate that they contain one molecule of parent nucleoside and one molecule of reactant amine. Upon standing in water these products revert to parent hydrate, while heating produces parent nucleoside. Less comprehensive studies indicate that photohydrates of dUrd and dCyd undergo analogous thermal reactions. Preliminary results suggest that UV-irradiated polyuridylic acid and polycytidylic acid undergo similar reactions. These results may have relevance for obtaining a complete understanding of the biological effects of producing Urd and dCyd photohydrates in a cellular environment.

Downsizing of Enzymes by Chemical Methods: Arginine Mimics with Low pKa Values Increase the Rates of Hydrolysis of RNA Model Compounds

This thesis addresses structure and reactivity of polypeptide catalysts in reactions that mimic the hydrolysis of RNA and DNA. A designed helix-loop-helix motif was used as a scaffold where the amino acid residues were systematically varied. The reactivity of a previously reported catalyst, HNI, was evaluated and the catalytic residues of the active site, Arg and His, were replaced in a stepwise manner by the artificial amino acid Gcp. Gcp has a guanidinocarbonyl pyrrole side chain, i.e. a side chain that mimics that of Arg but with a lower pKa. Gcp was used to replace both histidine and arginine in the polypeptide catalysts and was able to bind phosphate as well as carry out general base catalysis. The parent polypeptide HNI was shown to catalyse phosphoryl transfer reactions of phosphodiesters in an active site with two His and two Arg residues. The performance of the active site was improved by the introduction of two Tyr residues to form the catalyst HJ1 designed to provide nucleophilic catalysis in the hydrolysis of DNA model substrates. To improve the catalytic activity beyond that of HJI, Gcp was introduced to replace Arg and His residues in the HN1 scaffold. The designed catalyst JL3 was capable of a 150-fold rate enhancement compared to HNI in the reaction of the substrate HPNP, representing the first step in RNA hydrolysis. Mechanistic studies of JL3 catalysis suggested that the pKa value of the Gcp residue in the folded polypeptides was around 5. In combination with the observation of a solvent kinetic isotope effect of 1.7 the Gcp residue was proposed to provide general base catalysis and transition state stabilisation in the reaction of uridine 3′-2,2,2-trichloroethylphosphate, a realistic RNA model with a leaving group pKa of 12.5. The JL3 polypeptide catalyst followed saturation kinetics with a kcat/KM of 1.08 x 10-3 M-1s-1. The introduction of a designed photoswitchable amino acid in a catalytic polypeptide allowed the activity of the polypeptide in the reaction with an activated ester to be under photochemical control. Photoisomerization of this switch altered the structure of the polypeptide and affected the catalytic activity of the polypeptide catalyst. The chemical synthesis of designed molecules expands the amino acid alphabet and makes it possible to downsize enzymatic functions. It opens up possibilities for the production of novel biocatalysts that can catalyse natural as well as non-natural reactions.

Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease.

Bilirubin, an antioxidant in the blood, plays a role in protection from atherosclerosis. The level of bilirubin is highly correlated to the incidence of coronary artery disease (CAD). Unconjugated bilirubin is conjugated with glucuronic acid through the reaction of uridine 5′-diphosphate-glucuronosyl transferase 1A1 (UGT1A1). The interactions of CAD and the variations in the coding regions of the UGT1A1 gene have never been evaluated. The purpose of this study was to analyze the influence of the UGT1A1 variant on the incidence of CAD. There were 135 participants in this study: 61 in the experimental group, who had CAD, and 74 in the control group, who did not have CAD. The blood samples from all 135 participants were collected and assayed to clarify the relationship between bilirubin and CAD. The assay of the polymerase chain reaction and the sequence of the UGT1A1 gene were examined to find the gene’s polymorphisms. The bilirubin levels for the participants in the control group were significantly higher than for the patients in the CAD group. Although the concentration of bilirubin in the UGT1A1 variant was higher than the wild type for the patients in the CAD group, there was no significant difference in the polymorphism of UGT1A1 between the patients in the CAD group and the participants in the control group.

Chemically Stabilized Phenylboranylidene Groups Having a Dimethoxytrityl Group as a Colorimetrically Detectable Protecting Group Designed forcis-1,2-Diol Functions of Ribonucleosides in the Solid-Phase Synthesis of m22,2G5‘ppT

To not only improve the inherently poor stability of the phenylboranylidene group as a protecting group of the 2',3'-cis-diol function of ribonucleosides but also introduce a colorimetrically detectable function into its mother structure, various 2-[(dialkylamino)methyl]phenylboronic acid derivatives having a [(4,4'-dimethoxytrityl)oxy]methyl group were synthesized. The reaction of uridine with these substituted phenylboronic acid derivatives gave the corresponding 2',3'-O-phenylboranylideneuridine derivatives. The stability of these phenylboranylidene groups was examined. As a result, it was shown that the steric hindrance around the amino group greatly influenced the stability of the 2-substituted phenylboranylidene groups. The 2-aminomethyl-5-[[(4,4'-dimethoxytrityl)oxy]methyl]phenylboranylidene group was the most stable. Its 2-dimethylamino counterpart, the 2-[(dimethylamino)methyl]-5-[[(4,4'-dimethoxytrityl)oxy]methyl]phenylboranylidene group, was the second most stable. When the most and second stable protecting groups were applied to the synthesis of m(2)(2,2)G(5)(')ppT on controlled pore glass, the second stable protecting group showed the best result. The use of this DMTr-containing protecting group enabled us to estimate colorimetrically the amount of the m(2)(2,2)G residue that was incorporated into the reactive site of the pT-loaded CPG resin.

Equilibrium and NMR Studies of Noncovalent Interactions in Binary Systems: Uridine, Adenosine, Cytidine and Thymidine, and Adenosine (or Cytidine) 5?-Monophosphate in Aqueous Solution

The molecular complex formation reactions of uridine (Urd) with adenosine (Ado), cytidine (Cyd), thymidine (Thd), adenosine 5′-monophosphate (AMP) and cytidine 5′-monophosphate (CMP) have been studied at 20°C. It was found that the main positive noncovalent centers of ion–dipole and dipole–dipole type interactions are the protonated N(3) atoms of Urd, whereas the negative centers are the endocyclic atoms of the bases characterized by high electron density from the second molecule involved in the reaction. Moreover, NMR results indicate the occurrence of stacking in the complex (Urd)H(Cyd), whereas in the complex, (Urd)H2(Thd), it is the only type of interaction. Deprotonation of the latter species brings about a change in the character of the reaction and ion–dipole interactions have been detected in the adduct, (Urd)H(Thd). Interestingly, no involvement of the phosphate groups in the formation of AMP and CMP adducts has been evidenced and the main centers of the reactions were found to be the N(7)and N(1) atoms of AMP, or the N(3) atoms of CMP and Urd. Moreover, in the Urd/CMP system the NMR results suggest stacking-type interactions.

ChemInform Abstract: Synthesis, Structure and Reactions of Uridine 2′‐C,3′‐O‐γ‐Butyrolactone: Versatile Intermediate for the Synthesis of 2′‐C‐Branched Nucleosides.

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.

Synthesis, structure and reactions of uridine 2′-C,3′-O-γ-butyrolactone: versatile intermediate for the synthesis of 2′-C-branched nucleosides

Uridine 2′-C-3′-O-γ-butyrolactone 5a has been prepared by cyclisation of 2′-α-C-carboxymethyl-2′-deoxyuridine 8 in acetic acid–methanol. Detailed 1H NMR studies on compound 5a clearly demonstrate cis fusion between the γ-lactone and the sugar moiety, and determination of conformationally averaged structural descriptors, i.e. the pseudorotation phase angle and the puckering amplitude, suggests that the dominant conformer of the furanose ring is S. The 2′-C,3′-O-lactone 5a and its 5′-protected derivatives (5b and 5c) readily undergo aminolyses to yield a range of amide derivatives. Reaction with 5′-amino-5′-deoxythymidine gave a 2′–5′-amide-linked analogue of a dinucleoside monophosphate. Under acidic conditions the amides slowly relactonised. The 5′-protected lactones were also shown to react with simple organometallic reagents.

Characterization of platinum(II)-phosphato complexes of uridine nucleotides

Reactions of uridine 5'-di- and -triphosphates with cis-diamminedichloroplatinum(II) at or near neutral pH yielded substantial phosphato chelates. Each nucleotide afforded a pair of diastereomers due to the creation of an asymmetric center at the α- and β-phosphorus atoms of the UDP and UTP upon complexation to platinum(II). In addition to the phosphato complexes, nitrogen (N(3)) bound complexes are also formed.

ChemInform Abstract: The Photocycloaddition Reactions of Uridine and Related Compounds with 2,3‐Dimethyl‐2‐butene.

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.

High-Performance Liquid Chromatographic Characterization of the Role of Inorganic Pyrophosphatase in Regulating the Reaction of Uridine 5′-Triphosphate with Glucose 1-Monophosphate

Abstract Inorganic pyrophosphatase (EC 3. 6. 1. 1) drived the reaction of uridine 5′-triphosphate with glucose 1-monophosphate in the direction of uridine 5′-diphosphoglucose formation.

Photochemical synthesis of 5‐alkylpyrimidine nucleosides

Abstract5‐Alkylpyrimidine nucleosides, bearing different functional groups attached to the newly formed carbon chains at C‐5, were synthesized via a photocoupling reaction. 5‐(2‐Hydroxyethyl)uridine and its derivatives were obtained from the reaction of uridine (U) or 2′‐deoxyuridine (DU) with 2‐iodoethanol. Trimethylsilyl derivatives of 5‐iodouridine (IU) and 5‐iodo‐2′‐deoxyuridine (IDU), when treated with methyl acrylate, gave methyl 3‐(5‐uridinyl)propenoate and methyl 3‐(2′‐deoxy‐5–uridinyl) propenoate, respectively, which, upon catalytic hydrogenation, afforded 5‐[2‐(methoxy‐carbonyl)ethyl]uridine and its 2‐deoxyuridine analogue. IU and IDU also gave 5‐(2‐cyano‐ethenyl(uridine and its 2′‐deoxyuridine analogue, when treated with acrylonitrile. The latter compounds gave the corresponding 5‐(2‐cyanoethyl) nucleosides when subjected to catalytic hydrogenation.

Oligomerization of activated derivatives of 3'-amino-3'-deoxyguanosine on poly(C) and poly(dC) templates.

3'-amino-3'-deoxyuridine reacts with the nucleoside 5'-phosphorimidazolides in aqueous solution to give dinucleoside phosphoramidates. The reactions are one to two orders of magnitude faster than the corresponding reactions of uridine. In the presence of poly(C) or poly(dC) it is known that guanosine-5'-phosphorimidazolide does not condense efficiently or regiospecifically. However, the introduction of a methyl group at the 2-position of the imidazole ring leads to efficient synthesis of long 3'-5'-linked oligomers. The corresponding imidazole derivatives of 3'-amino-3'-deoxyguanosine-5'-phosphate both condense on these templates to give virtually identical families of products. Our results suggest that the intrinsically greater nucleophilicity of the amine groups will permit a much wider range of efficient template-directed syntheses with 3'-amino-3'-deoxynucleoside derivatives than with the corresponding derivatives of the parent nucleosides.

Reaction of uridine and uridine 5'-phosphate with diiminosuccinonitrile and cyanogen bromide in aqueous solution. Direct synthesis of the 2,2'-anhydronucleoside linkage at 2.degree.C

Reaction of uridine and uridine 5'-phosphate with diiminosuccinonitrile and cyanogen bromide in aqueous solution. Direct synthesis of the 2,2'-anhydronucleoside linkage at 2.degree.C

ChemInform Abstract: STUDIES ON NUCLEOSIDES AND NUCLEOTIDES. VIII. PREPARATION AND REACTIONS OF TRIPHENYLPHOSPHORANEDIYLNUCLEOSIDES

AbstractDie Reaktion der Nucleoside (Ia)‐(Id) mit den Reagenzien (II)+(III) führt zur Bildung der Phosphorandiylcyclonucleoside (IV) bzw. (V), deren Umsetzung mit verschiedenen Nucleophilen bzw. Elektrophilen entsprechende Nucleosidderivate mit freien 2′‐ und 3′‐Hydroxygruppen, z.B. (VI), (VII), (VIII), (XI), liefern.

Uridine oligonucleotide synthesis by the reaction of uridine with tri-(imidazol-1-yl)phosphine

Uridine oligonucleotides have been synthesized using tri-(imidazol-1-yl)phosphine. The procedure involves two steps: (i) the reaction of uridine with tri-(imidazol-1-yl)phosphine (< 60 min) and (ii) the in situ oxidation of the resulting phosphite with iodine and water (10 min). Uridine oligonucleotides up to a hexamer were obtained in high yield at a tri-(imidazol-1-yl)phosphine to uridine ratio of 1.5 at –78 °C. The inter-ribonucleotidic linkage of the oligomer consists of 2′–5′– and 3′–5′-linkages, formed in the oxidation process. Additives such as metal cations and polynucleotides in the oxidation process showed a significant effect on the formation of the inter-nucleotidic linkage.

Reactions of uridine with copper(II) acetate dimer

Two groups of cis diols may be categorized according to their reaction with the dimer Cu 2(CH 3COO −) 4 in dimethylsulfoxide. Cis diols of the ribose class destroy the dimer, as is revealed by a shift of the visible absorption to larger wavelengths with a loss of intensity and by an increase in magnetic moment. Addition of a uridine class cis diol also results in a loss of intensity but without a shift in the characteristic dimer 715 nm absorption maximum and by little change in magnetic moment. A quantitative analysis is presented of the changes in the visible absorption intensity upon uridine addition. The dimer to monomer equilibrium of copper acetate is taken into account. One molecule of uridine as a twice deprotonated cis diolate (R) reacts with one mol of copper acetate dimer (CuA 2) with expulsion of two acetates (A) as acetic acid to give Cu 2A 2R. A second product is also formed. Only upon inclusion of a product tetranuclear complex composed of Cu 4A 4R 2 is there achieved a satisfactory quantitative description of the interactions over a 30 fold range of total Cu(II) concentration.

Preparation of 2'-deoxyribonucleosides and their 5-halogeno derivatives

Two routes are described for the synthesis of 2'-deoxyribonucleosides from ribonucleosides. The reaction of uridine (Ia) with acetyl bromide affords the acetylated 2'-bromo derivative IIIe (73%) and triacetyluridine (Ib; 7%). The tributyltin hydride reduction of the reaction mixture yields diacetyl-2'-deoxyuridine (IIIc; 71%) along with triacetyluridine (Ib; 8%). On reaction of 5-fluorouridine (Ic) with acetyl bromide, the triacetyl-5-fluorouridine (Id; 39%) and the diacetyl-2'-bromo derivative IIIg are obtained. The tributyltin hydride reduction of IIIg affords diacetyl-2'-deoxy-5-fluorouridine (IIIh; 47.5%, referred to Ic). The reaction of cyclouridine (IIa) with acetyl chloride and the subsequent tributyltin hydride reduction followed by methanolysis furnishes 2'-deoxyuridine (IIId; 88.5%, referred to IIa). Diphenyl carbonate (IV) is prepared by reaction of phosgene with phenol in pyridine. On reaction with N-bromosuccinimide, diacetyl-2'-deoxyuridine (IIIc) (2'-deoxyuridine IIId, resp.) affords di-O-acetyl-5-bromo-2'-deoxyuridine (IIIj; 78%) (5-bromo-2'-deoxyuridine IIIk; 43%, resp.).

Enzymatic synthesis and reactions of uridine 5′-(5-thio-α- d-glucopyranosyl pyrophosphate)

Uridine 5′-(5-thio-α- d-glucopyranosyl pyrophosphate), UDPTG, is an efficient substrate for yeast uridine 5′-( d-glucopyranosyl pyrophosphate), UDPG, pyrophosphorylase. K m for UDPTG with the pyrophosphorylase is 0.2 m m and the analog reacts with a maximal velocity 96% that of UDPG. UDPTG is also a substrate for yeast UDP-galactose 4-epimerase. Although not a substrate for bovine liver UDPG dehydrogenase, UDPTG is a potent, mixed-type inhibitor with respect to both UDPG and nicotinamide adenine dinucleotide (NAD). UDPTG is synthesized in 30% yield from 5-thio- d-glucopyranose and in 85% yield from 5-thio-α- d-glucopyranose 1-phosphate by using mixtures of commercially available enzymes. The p K a of the uracil moiety in UDPTG is the same as that in UDPG, and UDPTG appears to be similar to UDPG in the extent of secondary structural order. UDPTG, however, is more highly acid-labile than UDPG.

Uridine diphosphate 2-deoxyglucose: Chemical synthesis, enzymic oxidation and epimerization

The paper describes chemical synthesis of uridine diphosphate 2-deoxyglucose (UDPdGlc) through reaction of uridine 5′-phosphomorpholidate with 2-deoxy-α-d-glucopyranosyl phosphate. The prepared analog of uridine diphosphate glucose (UDPGlc) served as a substrate for calf liver UDPGlc dehydrogenase (EC 1.1.1.22), the reaction product was identified as nucleotide deoxyhexuronic acid derivative. The apparent Km for UDPdGlc was found to be 60 times that of UDPGlc, and the relative V value for the analog was 0.09. The peculiar lag-period in reaction kinetics has been observed for the analog, and is presumably connected with the slow rate of the initial stages of the reaction. UDPdGlc was found to be quite an efficient substrate for UDPGlc 4-epimerases (EC 5.1.3.2) from yeast, calf liver and mung bean seedlings.