Anomalous nucleosides

A preparative synthesis of the antimetabolite 6-azacytidine is described which involves the amination under mild conditions without the use of an autoclave of 2, 3, 5-tri-O-acyl-4-thip-6-azauridines with the isolation of the intermediate 2, 3, 5-tri-O-acyl-6-azacytidines and subsequent elimination of the protective groups at room temperature.For communication VI, see [10].     

Anomalous nucleosides

By the condensation of the mercury salt of benzotriazole with acetylpentosyl bromides in xylene, we have synthesized 1-benzotriazolyl-2,3, 4-tri-O-acetyl--D-ribo- and-xylopranosides, the deacetylation of which has given anomalous nucleosides- antimetabolites of nucleic metabolism: 1-benzotriazolyl--D-ribopyranoside and 1-benzotriazolyl-- D-xylopyranoside.For part IX, see [9].     

N-levulination of nucleosides

Procedures have been developed for the synthesis of the N-levulinyl derivatives of cytidine, adenosine and guanosine.     

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].     

Fluorescent derivatives of nucleosides

Fluorescence spectra of formycin anhydronucleosides 5,6,8 and of N-dimethylaminomethylene ribonucleosides 1b, 2, 3a-3c and 4 in aqueous solution at 5-7 × 10^?5 M are reported. Compounds 5 and 6 exhibit a very strong fluorescence emission, ca. 4 and 2 times more intense than that of formycin ( 1a ) accompanied by a bathochromic shift of the emission maximum. Anhydronucleoside 8 also has an increased fluorescence intensity over the parent nucleoside 7 . The level of fluorescence emission is lower in 7 and 8 than in 1a , 5 or 6 . Introduction of N-dimethylaminomethylene group into 1a (compound 1b ) caused a decrease in the fluorescence intensity relative to 1a but a bathochromic shift of the emission maximum. In other instances (compounds 2, 3a-3c, 4 ) the introduction of N-dimethylaminomethylene group led also to fluorescent derivatives. This effect is most pronounced with 2 , whereas the fluorescence intensity of the rest of the group ( 3a-3c and 4 ) is much lower. Compounds 3c and 4 exhibit, however, a profound bathochromic shift in the fluorescence emission maximum relative to 2, 3a or 3b . A possible relationship of the fluorescence emission to the base conformation in formycin and potential use of N-dimethylaminomethylene nucleoside and nucleotide derivatives as fluorescent probes are discussed. J. Heterocyclic Chem., 14 , 135 (1977).     

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].     

核苷研究2: 苄基糖核苷的立体选择性合成

1-(2, 3, 4, 6-O-四苄基吡喃糖基)-三氟乙酸酯或三氯乙酸酯在无水四氯化锡存在下与一些具有代表性的硅醚保护的碱基或者含氮杂环化合物反应, 合成了一系列新的苄基糖苷。对三氟乙酰氧基、三氯乙酰氧基作为新的离去基在核苷合成中的反应活性、立体选择性和反应收率进行了讨论。     

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.     

Alkylating nucleosides. 3. The reaction of 3,5-dimethylpyrazole nucleosides with N-bromosuccinimide

Bromination of 3,5-dimethylpyrazole nucleosides with N-bromosuccinimide gave the corresponding 4-bromo-3,5-dimethylpyrazole, 3-methyl-5-(bromomethyl)pyrazole and 4-bromo-3-methyl-5-(bromomethyl)pyrazole nucleosides. Structural assignments were made on basis of analytical and ¹ H nmr spectral data. All of the bromomethylpyrazole nucleosides described showed cytostatic activity against HeLa cell sultures.     

Enzymatic phosphorylation of unnatural nucleosides

In an effort to expand the genetic alphabet, a number of unnatural, predominantly hydrophobic, nucleoside analogues have been developed which pair selectively in duplex DNA and during enzymatic synthesis. Significant progress has been made toward the efficient in vitro replication of DNA containing these base pairs. However, the in vivo expansion of the genetic alphabet will require that the unnatural nucleoside triphosphates be available within the cell at sufficient concentrations for DNA replication. We report our initial efforts toward the development of an unnatural in vivo nucleoside phosphorylation pathway that is based on nucleoside salvage enzymes. The first step of this pathway is catalyzed by the D. melanogaster nucleoside kinase, which catalyzes the phosphorylation of nucleosides to the corresponding monophosphates. We demonstrate that each unnatural nucleoside is phosphorylated with a rate that should be sufficient for the in vivo replication of DNA.