Analogs of pyrimidine mono- and polynucleotides

Phosphorylation of N₁-(1,4-dihydroxy-2-butyl) derivatives of uracil and thymine with polyphosphoric acid or Β-cyanoethyl phosphate in the presence of dicyclohexylcarbodiimide gives the corresponding diphosphates as the chief reaction products.     

Analogs of pyrimidine mono- and polynucleotides

The phosphorylation of N₁-(l,4-dihydroxy-2-butyl) thymlne with β-cyanoethyl phosphate in the presence of dicyclohexylcarbodiimide was investigated. The optimum conditions for the specific synthesis of the diphosphate, the isomeric monophosphates, and the cyclophosphate of N₁-(l,4-dihydroxy-2-butyl)thyimine were found. A number of side products were identified, and the fundamental ideas regarding the reaction mechanism are given. It is shown that the “pseudoglycoside” bond in the synthesized compounds is more resistant to acid hydrolysis than the analogous bond in the natural prototypes.     

Analogs of purine nucleosides and purine mono- and polynucleotides

On the basis of a comparison of the protolysis constants and vibrational frequencies it is shown that intermolecular interactions are present in 6-substituted 9-(,-dihydroxyalkyl)-purines and the corresponding mono- and diphosphates. In addition, in the case of the phosphates the existence of intramolecular interactions of electrostatic character between the phosphate group and the heteroring is also proposed. A comparison of the protolysis constants provides evidence for the different character of the interaction of the dihydroxyalkyl residue with the heteroring of the base in series of adenine and hypoxanthine derivatives.See [1] for communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1684–1689, December, 1974.     

Analogs of purine nucleosides and purine mono- and polynucleotides

Phosphorylation of 6-substituted 9-(1, 5-dihydroxy-3-pentyl)purines with 2-cyanoethyl phosphate in the presence of dicyclohexylcarbodiimide in anhydrous pyridine gave their 1, 5-diphosphates. Oligomers containing pyrophosphate and ester bonds were obtained by polycondensation of 1, 5-diphosphates of 6-dimethylamino- and 6-oxo-9-(1, 5-dihydroxy-3-pentyl)purines with the appropriate 9-(1, 5-dihydroxy-3-pentyl) purines.See [1] for communication V.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 693–696, May, 1976.     

Analogs of purine nucleosides and purine mono- and polynucleotides

Selective protection of the amino and one of the hydroxyl groups of 6-substituted 9-(α,ω-dihydroxy-2-alkyl)purines was realized. A convenient method for the preparation of monophosphates was developed.     

Analogs of pyrimidine mono- and polynucleotides. V. Synthesis of models of di- and trinucleotides by thermal polycondensation

Analogs of di- and trinucleotides were synthesized by thermal polycondensation of N₁-(1,4-dihydroxy-2-butyl)thymime with a mixture of its isomeric monophosphates. The model compounds do not react with polyadenylic acid. The dinucleotide analog suppresses the synthesis of polyphenylalanine in the polyuridylic acid matrix.     

Analogs of pyrimidine nucleosides

The UV absorption spectra of 5-substituted N¹-(tetrahydrofuran-2-yl)- and N¹-(2oxotetrahydrofuran-3-yl)uracils have been studied and their protolysis constants have been determined by the spectrophotometric method. A comparison is given with the spectra and pKa values of the corresponding N¹-methyl derivatives and ribosides and deoxyribosides.For part IV see [11].The work was carried out with analytical samples of compounds obtained by us previously [9–12].     

Analogs of pyrimidine nucleosides

N₁-(-Tetrahydrofuranyl)- and N₁-(-tetrahydropyranyl)uracils and the corresponding 6-azauracils have been obtained by the condensation of bistrimethylsilyl derivatives of uracils and 6-azauracils with-chlorotetrahydrofuran and-chlorotetrahydropyran. The superiority of the silyl method over the mercury method used previously has been demonstrated.For part III, see [9].     

Analogs of pyrimidine nucleosides

α-(1-Cytosinyl)-γ-butyrolactone was obtained by condensation of bis(trimethylsilyl)cytosine with α-bromobutyrolactone. The reduction of α-(1-cytosinyl)-γ-butyrolactone with sodium borohydride gave N₁-(1,4-dihydroxy-2-butyl)cytosine, the acylation of which with benzoyl chloride and subsequent partial hydrolysis gave N₁-(1,4-dihydroxy-2-butyl)-N₄-benzoylcytosine.     

Analogs of pyrimidine nucleosides

The reaction of alkoxy bromides with N₁-(-tetrahydrofuryl) derivatives of pyrimidine bases has given a series of 6-alkoxy-5-bromo-1-(-tetrahydrofuryl)-5, 6-dihydrouracils. The hydrogenation of the 1-(-tetrahydrofuryl) derivatives of uracil and of 5-fluorouracil has been studied. It has been shown that in both cases 1-(-tetrahydrofuryl)-5, 6-dihydrouracil is formed.     

Analogs of pyrimidine nucleosides

A number of N₁-(-butyrolactono) derivatives of 5-substituted uracils have been synthesized by condensing the sodium derivatives of the corresponding bases with -bromobutyrolactone or by the halogenation of N₁-(-butyrolactono)uracil.For part I, see [1].     

Analogs of pyrimidine nucleosides

A new method was developed for the synthesis of 1-(2-tetrahydrofuryl) derivatives of uracil, 5-substituted uracils, 6-azauracil, and cytosine by alkylation of 2,4-bis(trimethylsilyl) derivatives of pyrimidine bases with 2-acetoxytetrahydrofuran in the presence of Lewis acids. In contrast to 2-chlorotetrahydrofuran, which is used in a previously described method, 2-acetoxytetrahydrofuran is stable at room temperature and reacts under these conditions with silyl derivatives of uracils in the presence of SnCl₄ to give 1-(2-tetrahydrofuryl) derivatives of pyrimidine bases in 80–85% yields.See [1] for communication X.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedineaii, No. 9, pp. 1258–1259. September, 1977.     

Analogs of pyrimidine nucleosides

A new method for the synthesis ofN₁-(dihydroxyalkyl)uracils by reduction of substituted α- (1-uracilyl)- and γ-[(1-uracilyl)methyl]-γ-butyrolactones with sodium borohydride was found.     

Analogs of purine nucleosides and purine mono-and polynucleotides

A number of 6-substituted 9-(1,5-dihydroxy-3-pentyl)purines were obtained from 5-amino-4,6-dichloropyrimidine. 5-Amino-4,6-dichloropyrimidine reacts with 2-hydroxymethylpyrrolidine to give 4-chloro-5-amino-6-(2-hydroxymethylpyrrolidino)pyrimidine.See [1] for communication IV.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 552–555, April, 1976.     

Analogs of the pyrimidine nucleosides

The kinetics of the hydrolysis of the pseudoglycosidic C-N bond in the N¹-derivatives of uracil, thymine, and 5-fluorouracil at various pH values of the medium have been studied. The dependence of the rate of hydrolysis of N¹-(tetrahydrofuran 2-yl)-5-fluorouracil on the temperature has been investigated. The influence of substituants at C₅ and N₁ of the pyrimidine ring on the stability of the pseudoglycosidic C-N bond has been evaluated.For part V, see [10].     

Femtosecond electron-transfer reactions in mono- and polynucleotides and in DNA

Quenching of redox active, intercalating dyes by guanine bases in DNA can occur on a femtosecond time scale both in DNA and in nucleotide complexes. Notwithstanding the ultrafast rate coefficients, we find that a classical, nonadiabatic Marcus model for electron transfer explains the experimental observations, which allows us to estimate the electronic coupling (330 cm(-1)) and reorganization (8070 cm(-1)) energies involved for thionine-[poly(dG-dC)](2) complexes. Making the simplifying assumption that other charged, pi-stacked DNA intercalators also have approximately these same values, the electron-transfer rate coefficients as a function of the driving force, DeltaG, are derived for similar molecules. The rate of electron transfer is found to be independent of the speed of molecular reorientation. Electron transfer to the thionine singlet excited state from DNA obtained from calf thymus, salmon testes, and the bacterium, micrococcus luteus (lysodeikticus) containing different fractions of G-C pairs, has also been studied. Using a Monte Carlo model for electron transfer in DNA and allowing for reaction of the dye with the nearest 10 bases in the chain, the distance dependence scaling parameter, beta, is found to be 0.8 +/- 0.1 A(-1). The model also predicts the redox potential for guanine dimers, and we find this to be close to the value for isolated guanine bases. Additionally, we find that the pyrimidine bases are barriers to efficient electron transfer within the superexchange limit, and we also infer from this model that the electrons do not cross between strands on the picosecond time scale; that is, the electronic coupling occurs predominantly through the pi-stack and is not increased substantially by the presence of hydrogen bonding within the duplex. We conclude that long-range electron transfer in DNA is not exceptionally fast as would be expected if DNA behaved as a "molecular wire" but nor is it as slow as is seen in proteins, which do not benefit from pi-stacking.     

Analogs of pyrimidine nucleosides. 20. Aminomethylation of 5-fluorouracil and thymine

Reactions were studied of 5-fluorouracil and thymine with formaldehyde and secondary amines (piperidine, morpholine) and also of their 2,4-bis(trimethylsilyl) derivatives with N-methoxymethylmorpholine and bis(amino)methanes. The N-aminomethylation products are slightly stable and in aqueous solutions decompose readily to the starting components; their structure was confirmed by PMR spectra.For Communication 19, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 90–93, January, 1987.     

Analogs of pyrimidine nucleosides. 13. 1-Substituted 4-thiouracils

4-Thiouracil derivatives with various oxygen-containing groupings as substituents attached to the N₁ atom were obtained by thionation of 1-substituted uracils with phosphorus pentasulfide. It is demonstrated that the yield of the 4-thiouracil derivative depends on the strength of the C-N pseudoglycoside bond in the starting 1-substituted uracil.See [1] for communication 12.Translated from Khimlya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1109–1113, August, 1980.