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Issue 0, 1982
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Syntheses of the two epimeric 5′-methylcytidines, their 5′-phosphates and [5-3H]-5′-pyrophosphates, and the two 5′-methyldeoxycytidines. A novel cystosine anhydro-nucleoside with two oxygen bridges between the base and the sugar

Abstract

In a series of experiments the starting materials were methyl 2,3-O-isopropylidene-β-D-alto- and -α-L-talofuranosides. These were converted in two steps into the corresponding 2,3,5-tri-O-benzoyl esters, (5) and (11), which were coupled with N-acetylbis(trimethylsilyl)cytosine in the presence of tin(IV) chloride, to the protected nucleosides (19) and (20). Alkaline methanolysis gave the free cytidine homologues, 1-(6-deoxy-β-D-alto- and -α-L-talo-furanosyl)cytosine (23) and (28), which were converted into the crystalline 5′-phosphates (24) and (29), and hence to the dilithium salts of the 5′-pyrophosphates, (25) and (30), by standard procedures. These were labelled at C-5 by bromination, followed by catalytic reduction in tritium gas. The same methyl furanoside starting materials were converted into the 3,5-dibenzoates, (3) and (9), by deacetalation followed by monobenzoylation by the stannylene procedure. Substitution of iodine via the 2-trifluoromethanesulphonates gave iodides which were reduced by tributylstannane to methyl 3,5-di-O-benzoyl-2,6-dideoxy-β-D-ribo- and -α-L-lyxo-hexofuranosides (7) and (13). Coupling of these in the same way as above, followed by alkaline methanolysis, gave the two deoxycytidine homologues, 1-(2,6-dideoxy-β-D-ribo- and -α-L-lyxo-hexofuranosyl)cytosine, (16) and (17), together with their anomers (14) and (15). In another approach to these nucleosides, 4-N-acetyl-2′,3′-O-isopropylidenecytidine was oxidized to the aldehyde (33) which was condensed with dimethylsuiphoxonium methylide to a mixture of epoxides (34) and (35). Hydrogen bromide opening, followed by tributylstannane reduction, converted these epoxides into 4-N-acetyl-1-(2,3-O-isopropylidene-6-deoxy-β-D-allo- and -α-L-talo-furanosyl)cytosine (36) and (37). Treatment of the same mixture dissolved in tetrahydrofuran (THF) by boron trifluorideether gave 4-acetamido-1-(2,5′; 2,6′-dianhydro-2′,3′-O-isopropylidene-α-L-talofuranosyl)-2H-pyrimidine (39), the first reported anhydro-nucleoside with two oxygen bridges between the base and the sugar, available in 18% overall yield from protected cytidine.

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Article type: Paper
DOI: 10.1039/P19820000385
J. Chem. Soc., Perkin Trans. 1, 1982, 385-393

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    Syntheses of the two epimeric 5′-methylcytidines, their 5′-phosphates and [5-3H]-5′-pyrophosphates, and the two 5′-methyldeoxycytidines. A novel cystosine anhydro-nucleoside with two oxygen bridges between the base and the sugar

    S. David and G. de Sennyey, J. Chem. Soc., Perkin Trans. 1, 1982, 385
    DOI: 10.1039/P19820000385

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