Pyrazole C-nucleoside Research Articles

Sydnone Ribosides as a Platform for the Synthesis of Pyrazole C-Nucleosides: A Unified Synthesis of Formycin B and Pyrazofurin.

The C-nucleoside natural products formycin B and pyrazofurin were synthesized in seven steps employing a sydnone riboside as common intermediate. Sydnone ribosides were synthesized via a direct Lewis acid catalyzed dehydrative glycosylation reaction. We demonstrated that these can be used for the diversity-oriented synthesis of pyrazole C-nucleoside analogues via thermal 1,3-dipolar cycloaddition reactions with various alkynes, giving access to the pyrazole C-nucleoside natural products, as well as opening new avenues for exploring nucleoside chemical space.

ChemInform Abstract: Synthetic Studies of Imidazole C‐Nucleosides Toward Biofunctional Molecules

AbstractReview: 35 refs.

Synthetic Studies of Imidazole C-Nucleosides toward Biofunctional Molecules

Synthetic studies of C4-linked imidazole C-nucleosides toward biofunctional molecules are described, in which the following items are covered. 1) Stereoselective synthesis of imidazole C- and pyrazole C-nucleosides via diazafulvene intermediates. 2) Synthesis of tetrahydrofuranylimidazoles using a PhSe group efficiently and its application to the new human histamine H(3) receptor (hH(3)R) agonist, imifuramine, and the first selective human histamine H(4) receptor (hH(4)R) agonist, OUP-16. 3) Synthesis of imidazole ribonucleoside phosphoramidite (Imz-PA) with pivaloyloxymethyl (POM) group for probing the catalytic mechanism of ribozymes. 4) Synthesis of a two-carbon-elongated homologue (Imz-C(2)-PA) with a combination of POM and 2-cyanoethyl groups. 5) Incorporation of C(2)-imidazole nucleoside into position 638 of VS ribozyme using Imz-C(2)-PA and catalytic activities of the thereby generated modified VS ribozyme (G638C(2)Imz).

New Trends in Synthesis of Pyrazole Nucleosides as New Antimetabolites

Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation, chemical properties, biological activities, and structure-activity relationships, with emphasis to selected drugs or drug candidates. Two pyrazole C-nucleoside compounds pyrazofurin (pyrazomycin) and its α-epimer pyrazofurin B are active components of potent antivirals approved for therapeutic use in human medicine aimed against various diseases caused by DNA viruses.

Synthesis of pyrazole C-nucleosides via Tin(IV) chloride-promoted reactions of β- d-ribofuranosyl cyanide with β-dicarbonyl compounds

2,3,5-Tri- O-benzoyl-β- d-ribofuranosyl cyanide reacts with methyl acetoacetate and diethyl malonate in the presence of stoichiometric amounts of SnCl 4 to give a β- d-ribofuranosyl-enaminoketoester and a β- d-ribofuranosyl-enaminodiester, respectively. The β- d-ribofuranosyl-enaminoketoester was debenzoylated, treated with 2,2-dimethoxypropane and tert-butyl-dimethylsilyl chloride to give the methyl 3-amino-3-(5′- O- tert-butyldimethylsilyl-2′,3′- O-isopropylidene-β- d-ribofuranosyl)-2-acetyl propanoate obtained in good yield together with small amounts of its α-anomer. The reactions of the β-anomer with hydrazine, methyl- and phenylhydrazine, carried out under controlled experimental conditions, afforded the pyrazole C-nucleosides in good yields as β-anomers.

Stereospecific synthesis of two novel cytotoxic pyrazole C-nucleosides from d-glucose

A multistep stereospecific synthesis of two novel pyrazole C-nucleosides 12 and 21 has been achieved starting from d-glucose, by utilizing the 2,5-anhydro- d-glucose ethylene acetal derivative 1 as a divergent intermediate. The C-nucleoside 12 was shown to be a moderate inhibitor of the in vitro growth of N2a and BHK 21 tumor cell lines, whereas 21 showed a moderate cytotoxic activity only against N2a cells.

Synthesis of 4-(4,6-di- O-benzyl-2,3-dideoxy- β- d- erythro-hex-2-enopyranosyl)pyrazoles from 3,4,6-tri- O-acetyl- d-glucal

3-(4,6-Di- O-benzyl-2,3-dideoxy- β- d- erythro-hex-2-enopyranosyl)-2,4-pentanedione and its analogue 2-(4,6-di- O-benzyl-2,3-dideoxy- β- d- erythro-hex-2-enopyranosyl)-1-phenyl-1,3-butanedione, prepared from 3,4,6-tri- O-acetyl-1,5-anhydro-2-deoxy- d- arabino-hex-1-enitol (3,4,6-tri- O-acetyl- d-glucal), reacted with hydrazine and its methyl-, phenyl-, p-tolyl, and p-methoxyphenyl- derivatives in ethanol, at room temperature, to afford, in 71–96% yields, a series of 4-(4,6-di- O-benzyl-2,3-dideoxy- β- d- erythro-hex-2-enopyranosyl)-3-methylpyrazoles having the N-1 free or substituted by the foregoing groups, and the C-5 substituted by a methyl or phenyl group. The reactions of the 1-phenyl-1,3-butanedione derivative were highly regioselective. Catalytic hydrogenation of some of these novel compounds gave the respective 4′,6′-di- O-deprotected-2′,3′-saturated compounds in 51–67% yields. The acetolysis/methanolysis of one of the title compounds led to the formation of the 4′,6′-di- O-debenzylated 2′,3′-unsaturated pyrazole C-nucleoside in poor yield.