One-step to get 5-azidomethyl-2′-deoxyuridine from 5-hydroxymethyl-2′-deoxyuridine and detection of it through click reaction

Nowadays a few ways to synthesize 5-azidomethyl-2′-deoxyuridine from 5-hydroxymethyl-2′-deoxyuridine have been reported. But none of them was one-step. And many of them need to protect the hydroxyl group on the pentose ring. The detection of 5-hydroxymethyl-2′-deoxyuridine is also very important in many biological processes. However few fluorescence detection strategies have been tried to do this. Herein, we reported a one-step protocol to synthesize 5-azidomethyl-2′-deoxyuridine, which was then used for detecting 5-hydroxymethyl-2′-deoxyuridine through a click reaction.     

Synthesis of hapten-phosphoramidites from 2′-deoxyuridine

A total of 11 novel phosphoramidites, 3a-d, 4a-d and 14a-c were prepared from 2′-deoxyuridine functionalized at 5 and 6-position of the pyrimidine ring with hapten reporter groups, e.g. adamantane, carbazole, dansyl and dabsyl, suitable for use in immunodetection nucleic acid testing assays.     

5′-Noraristeromycin derivatives isomeric to aristeromycin and 2′-deoxyaristeromycin

A straightforward synthesis of (1S,2R,3R,4R)-4-(6-aminopurin-9-yl)-2-hydroxymethylcyclopentane-1,3-diol (2), an isomer of aristeromycin, and its 2′-deoxy derivative 3 from readily available disubstituted cyclopentenes is presented. An antiviral analysis of 2 showed it to have significant activity versus Epstein-Barr virus (IC₅₀ 0.62 μg/mL in the Elisa assay) and to be free of cytotoxicity effects against the host cells. In a much less comprehensive antiviral analysis, 3 also was active towards Epstein-Barr (IC₅₀ 7.58 μg/mL in the Elisa assay) but this was accompanied by cellular toxicity.     

Novel and efficient syntheses of 3′,5′-diamino derivatives of 2′,3′,5′-trideoxycytidine and 2′,3′,5′-trideoxyadenosine. Protonation behavior of 3′,5′-diaminonucleosides

High yielding synthetic routes to 3′,5′-diamino-2′,3′,5′-trideoxycytidine and 3′,5′-diamino-2′,3′,5′-trideoxyadenosine are described. In addition, the protonation behavior of 3′,5′-diamino-2′,3′,5′-trideoxycytidine, 3′,5′-diamino-2′,3′,5′-trideoxyadenosine, 3′,5′-diamino-3′,5′-dideoxythymidine, and 3′,5′-diamino-2′,3′,5′-trideoxyuridine has been studied by means of pH-metric measurements and NMR spectroscopy. The ionization constants and the sequence of protonation sites have been determined.     

New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides

A short, efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.     

Synthesis,cytotoxicity and antiviral activity studies of the conjugates of cobalt bis(1,2-dicarbollide)(-I) with 5-ethynyl-2′-deoxyuridine and its cyclic derivatives

A series of novel conjugates of cobalt bis(1,2-dicarbollide)(-I) with 5-ethynyl-2′-deoxyuridine and its cyclic derivatives were synthesized. Conjugates with 5-ethynyl-2-deoxyuridine were prepared by the direct Sonogashira coupling of a series of cobalt bis(1,2-dicarbollide)(-I) terminal alkynes and 5-iodo-2′-deoxyuridine. Their furo[2,3-d]pyrimidin-2(3H)-one isomers were obtained either by intermolecular cyclization of the above conjugates or by Sonogashira coupling using Pd/C as a catalyst. Action of ammonia on these furo[2,3-d]pyrimidin-2(3H)-one conjugates resulted in pyrrolo[2,3-d]pyrimidin-2(3H)-one conjugates. Most of the designed compounds have shown low cytotoxicity in several cell lines. Some 5-ethynyl-2-deoxyuridine and furo[2,3-d]pyrimidin-2(3H)-one conjugates have also presented antiviral activity.     

A versatile reagent for the synthesis of 5′-phosphorylated, 5′-thiophosphorylated or 5′-phosphoramidate-conjugated oligonucleotides

We report the synthesis of a new phosphorylating reagent that is easily accessible and allows not only the chemical synthesis of 5′-phosphorylated and 5′-thiophosphorylated oligonucleotides but also the 5′-conjugation through a phosphoramidate linkage. 5′-Amino-linker and 5′-alkyne oligonucleotides were obtained and the latter was conjugated by a 1,3-dipolar cycloaddition (click chemistry) with a galactosylated azide derivative to afford 5′-galactosyl oligonucleotide with high efficiency.     

Straightforward synthesis of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes via 2′,3′-O-orthoester group elimination: a simple route to 3′,4′-didehydronucleosides

Straightforward, high-yielding syntheses of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes and 3′-deoxy-3′,4′-didehydronucleosides starting from 2′,3′-O-orthoester derivatives of ribonucleosides are described.     

A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine

A short and concise synthesis of isofagomine derivatives via the epoxidation of chiral N-Boc-5-hydroxy-3-piperidene, followed by regioselective epoxide ring opening is described. This constitutes the first reported synthesis of homoisofagomine and the 5′-deoxyisofagomine.     

New reagent for the preparation of oligonucleotides involving a 5′-thiophosphate or a 5′-phosphate group

We report here a novel, simple reagent enabling the chemical incorporation of a thiophosphate or a phosphate group at the 5′-end of oligonucleotides using very mild basic deprotection conditions. This method can be useful in the case of alkali sensitive modified oligonucleotides. This reagent also gives access to the preparation of bifunctional oligonucleotides with either a thiophosphate group at the 5′-end and a phosphate at the 3′-end, or two thiophosphate groups at both the 5′- and the 3′-ends, or a 5′-thiophosphate group and a 3′-amino-containing linker.     

A short practical synthesis of 2′-deoxymugineic acid

A short and practical synthesis of 2′-deoxymugineic acid (DMA) has been developed via reductive alkylation with the aldehyde intermediates. No protection of azetidine-2-carboxylic acid was required and the presence of free carboxylic acid function facilitated purification by simple acid and base extractions. Furthermore, the intermediates were conveniently purified by HPLC due to the presence of chromophoric benzyl ester protecting group(s). Hydrogenolysis of the benzyl protecting groups in the final step furnished DMA in overall good yield.     

Synthesis of 8-halogenated-7-deaza-2′-deoxyguanosine as an 8-oxo-2′-deoxyguanosine analogue and evaluation of its base pairing properties

8-Halogenated-7-deaza-2′-deoxyguanosines (8-halo-7-deaza-dG) were designed to structurally mimic 8-oxo-2′-deoxyguanosine (8-oxo-dG), which is representative of an oxidized nucleoside. It has been shown by NMR that the conformation around the N-glycosidic bond of (8-halo-7-deaza-dG) is preferably syn, similar to 8-oxo-dG. The base pairing properties of 8-halo-7-deaza-dG were studied by measuring the thermal denaturation temperature of the duplexes, showing that their base pair with dC is destabilized compared with natural dG. These results also support their preference for syn conformation. Unlike 8-oxo-dG, 8-halo-7-deaza-dG did not form a stable base pair with dA, most likely due to the lack of N7-H hydrogen bonding with dA. In conclusion, the newly-designed 8-halo-7-deaza-dG analogs resemble 8-oxo-dG in its shape and preference for syn conformation, but they do not form Hoogsteen base pair with the opposing dA.     

Synthesis and crystal structure of 2′-deoxy-2′-fluoro-4′-thioribonucleosides: substrates for the synthesis of novel modified RNAs

We report herein the synthesis of appropriately protected 2′-deoxy-2′-fluoro-4′-thiouridine (5), -thiocytidine (7), and -thioadenosine (35) derivatives, substrates for the synthesis of novel modified RNAs. The synthesis of 5 and 7 was achieved via the reaction of 2,2′-O-anhydro-4′-thiouridine (3) with HF/pyridine in a manner similar to that of its 4′-O-congener whereas the synthesis of 35 from 4′-thioadenosine derivatives was unsuccessful. Accordingly, 35 was synthesized via the glycosylation of the fluorinated 4-thiosugar 25 with 6-chloropurine. The X-ray crystal structural analysis revealed that 2′-deoxy-2′-fluoro-4′-thiocytidine (8) adopted predominately the same C3′-endo conformation as 2′-deoxy-2′-fluorocytidine.     

The use of Cu and Zn salicylaldimine complexes as catalyst precursors in ring opening polymerization of lactides: ligand effects on polymer characteristics

A range of monomeric tetra‐coordinate copper (II) and zinc (II) complexes based on N,O‐bidentate salicylaldimine Schiff base ligands has been synthesized and characterized using various spectroscopic techniques. These complexes were then evaluated as initiators in ring‐opening polymerization of lactides at both 70 °C and 110 °C. The effect of structural changes in the complexes on the ability of these compounds to initiate lactide polymerization as well as the impact on the chemical and physical characteristics of the polymers obtained indicate that the coordination geometry of the metal complex, M? O bond length and substituents on the Schiff base ligand all play a role in the catalyst activity. Electronic factors were dominant in the case of the copper complexes while steric factors prevailed in the case of Zn initiators. Both the Zn and Cu complexes exhibit characteristics of living ring opening polymerization. Copyright © 2010 John Wiley & Sons, Ltd.     

Interaction of 2-(2′,6′-dialkylphenylazo)-4-methylphenols with iridium. C-H activation and migration of alkyl group

Reaction of 2-(2′,6′-diethylphenylazo)-4-methylphenol (L²) with [Ir(PPh₃)₃Cl] afforded two organoiridium complexes 3 and 4 via C-H bond activation of an ethyl group in the arylazo fragment of the L² ligand. In both the complexes the azo ligand binds to iridium as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride (in the case of complex 3) or chloride (in the case of complex 4) are also coordinated to the metal center. A similar reaction of [Ir(PPh₃)₃Cl] with 2-(2′,6′-diisopropylphenylazo)-4-methylphenol (L³) yielded another organoiridium complex 5, where migration of one iso-propyl group from its original location (say, the 2′ position) to the corresponding third position (say, the 4′ position) took place through C-C bond activation. In this complex the modified azo ligand binds to iridium as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. The structures of complexes 3 and 4 have been optimized through DFT calculations. The structure of complex 5 has been determined by X-ray crystallography. All the complexes show characteristic ¹H NMR signals and intense transitions in the visible region. Cyclic voltammetry on all the complexes shows an oxidation within 0.66-1.10 V vs SCE, followed by a second oxidation within 1.15-1.33 V vs SCE and a reduction within −0.96 to −1.07 V vs SCE.     

Novel oxorhenium complexes with 2-(2′-hydoxy-5′-methylphenyl)benzotriazolato ligand. X-ray studies,spectroscopic characterization and DFT calculations

The [ReOCl₂(hmpbta)(AsPh₃)] · MeCN, [ReOBr₂(hmpbta)(AsPh₃)] · MeCN, [ReOCl₂(hmpbta)(PPh₃)] · MeCN, [ReOBr₂(hmpbta)(PPh₃)] · MeCN, and [ReBr₂(hmpbta)(PPh₃)] · MeCN complexes have been prepared in the reactions of [ReOX₃(EPh₃)₂] (X = Cl, Br; E = P, As) with 2-(2’-hydoxy-5′-methylphenyl)benzotriazole in molar ratio 1:1. All the compounds were structurally and spectroscopically characterized. The electronic structure of [ReOCl₂(hmpbta)(AsPh₃)] has been calculated with the density functional theory (DFT) method. The TDDFT/PCM calculations have been employed to produce a hundred of singlet excited-states starting from the ground-state geometry optimized in the gas phase, and the UV–Vis spectrum of [ReOCl₂(hmpbta)(AsPh₃)] has been discussed on this basis. The paper reports also X-ray structure and DFT calculations for the disubstituted [ReOCl(hmpbta)₂] chelate.     

Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8a-c⁺·BF₄⁻) and related compounds 2a-c⁺·BF₄⁻, respectively. In the photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give desired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D₂ under degassed conditions, the details of the reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G^∗ basis set of the MP2 levels as well.     

2,2′,3,4-Tetrahydroxy-3′-sulpho-5′-nitroazobenzene for spectrophotometric determination of aluminium in pharmaceutical suspensions and granite

A selective and sensitive new spectrophotometric method has been developed for the determination of aluminium. 2,2′,3,4-Tetrahydroxy-3′-sulpho-5′-nitroazobenzene (tetrahydroxyazon SN) formed an orange chelate with aluminium at pH 4. Molar absorptivity of the complex in 1:2 is 5.46 × 10⁴ l mol⁻¹ cm⁻¹ at 479 nm. The method obeys Beer's law in the range of 0.005-1.079 μg ml⁻¹. The determination of aluminium is not interfered with by earth alkaline, alkaline elements, rare earth elements, halides, phosphates, sulphates, urea, ascorbic acid, Sn²⁺, Sr²⁺, Cr³⁺, Cd²⁺, Hg²⁺, or Mn²⁺. The proposed method is rapid and simple, and it has been successfully applied to the determination of aluminium in certified pharmaceutical suspension and granite.     

Facile acid-catalyzed condensation of 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone with phenols, methoxyaromatic systems and enols

Various phenols, methoxy aromatic compounds, 3- and 4-hydroxycoumarins and enols smoothly condense with 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone 1 in an acid medium producing 2-aryl/alkyl-2,2′-biindan-1,1′,3,3′-tetrones in high yields. The adducts of resorcinol, 1,3,5-trihydroxybenzene and α- and β-naphthols of 1 preferably remain in the intramolecular hemi-ketal form, confirmed by X-ray diffraction studies. On the other hand para and meta substituted phenols condense with 1 in an acid medium to produce 6 or 7 substituted 2′,4-spiro(1′,3′-indanedion)-indeno[3,2-b]chromenes in good yields.