Synthesis of novel carbocyclic nucleosides with a cyclopentenyl ring: Homocarbovir and analogues

Balo, Carmen; Blanco, J. M.; Fernández, Fernando Nieto; Lens, E.; López, Carmen

doi:10.1016/s0040-4020(98)83020-2

Cited by 14 publications

(7 citation statements)

References 11 publications

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“…Various carbovir analogues were synthesized by chemists, including 6 0 -(a)-methyl derivatives [56], 2 0 ,3 0 -fluoroderivatives [57], nor-derivatives [58], and homocarbovir [59]. Among these syntheses, Chu et al [60] presented a convenient preparation of the L-adenine analogue of carbovir, which exhibited moderately potent anti-HIV activity (EC 50 ¼ 2.4 mM), without cytotoxity up to 100 mM.…”

Section: G)mentioning

confidence: 99%

Synthesis and Biological Activity of Selected Carbocyclic Nucleosides

Mieczkowski

Agrofoglio

2008

Modified Nucleosides

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Nucleoside analogues are extremely useful for the development of therapeutic agents to control viral diseases and cancer. Replacement the oxygen of furanose ring of a nucleoside by a CH 2 unit results in carbocyclic nucleoside analogues. Carbocyclic nucleosides have emerged as targets of intense investigation due to their potent biological activity and greater metabolic activity and stability to nucleoside phosphorylases than the corresponding carbohydrate counterpart. Among these, aristeromycin (1), neplanocin (2), abacavir (3), lobucavir (4), synguanol (5) or the newly FDA-approved anti-HBV Baraclude Ò (6, Entecavir) ( Figure 15.1) are a few of the carbocyclic nucleosides that are useful antiviral drugs.The cellular processing and mechanism of action of carbocyclic nucleosides are, in general, similar to those of conventional nucleosides. They may undergo progressive phosphorylation to the corresponding mono-, di-, and triphosphates, and any of these activated forms may interact with natural cellular processes (Figure 15.2). On occasion, the interaction is innocuous and has little or no effect upon cell viability, but very often a significant inhibition of essential biochemical reactions occurs and in these cases measurable effects will be observable.One class of cellular enzymes to which carbocyclic nucleosides are not susceptible is the nucleoside phosphorylases, as a consequence of which they are extremely stable towards sugar-base cleavage. Most of those carbocyclic nucleosides which have been studied intensively are active as inhibitors of a viral enzyme (mainly a polymerase). Experience has shown that the essential structural features of carbocyclic nucleosides which must be retained are: the ability of the base to engage in base pairing with its DNA partner, and the presence of a 5 0 -hydroxyl group (or equivalent) which is capable of phosphorylation. The remainder of the sugar component can be regarded as a scaffold which ensures that the base pairing functionality and the 5 0 -phosphate (or phosphonate) are well distributed in space. The carbocyclic nucleosides do not have the same conformational data as the parent nucleosides; rather, in all cases they Modified Nucleosides: in Biochemistry, Biotechnology and Medicine. Edited by Piet Herdewijn

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Section: G)mentioning

confidence: 99%

Synthesis and Biological Activity of Selected Carbocyclic Nucleosides

Mieczkowski

Agrofoglio

2008

Modified Nucleosides

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“…performing a one-pot removal of the glucose moiety and reduction of the aglycone. Surprisingly, it proved possible Experimental Section to benzoylate positions 3, 6, and 10 selectively to give, in a moderate yield, tribenzoate 12c with the sterically hindered 13 C NMR: [D 6 ]DMSO (δ C ϭ fractions (566 mg) of 4a and 4b were treated with 0.1  NaOMe 39.5), [D 4 ]methanol (δ C ϭ 49.0), CDCl 3 (δ C ϭ 77.0); assignments in MeOH (20 ml) for 1 h at room temp. Then HOAc was added of 1 H-NMR spectra were based on 1D homonuclear decoupling until pH ϭ 7.…”

Section: Next Catalpol (2) Was Investigated As Starting Material; Itmentioning

confidence: 99%

“…Then HOAc was added of 1 H-NMR spectra were based on 1D homonuclear decoupling until pH ϭ 7. The solvent was evaporated, and the residue was experiments, while 13 C-NMR spectra were assigned by using carpurified by MPLC. Elution with H 2 O and then H 2 O/MeOH (10:1 bon-proton shift correlation spectra.…”

Section: Next Catalpol (2) Was Investigated As Starting Material; Itmentioning

confidence: 99%

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Synthesis of Carbocyclic Homo-N-Nucleosides from Iridoids

Franzyk¹,

Rasmussen

Mazzei

et al. 1998

Eur. J. Org. Chem.

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Two iridoid glucosides, antirrhinoside (1) and catalpol (2), were converted into selectively protected polysubstituted cyclopentylmethanols, which were subsequently used to prepare carbocyclic homo‐N‐nucleosides (5, 6 and 14). A purine moiety was introduced either by the Mitsunobu reaction or by substitution of a primary triflate with the tetrabutylammonium salt of 6‐iodopurine. The latter method was superior with regard to both ease of purification and yield. The N‐9 vs. N‐7 regioselectivity of the salts of different 6‐substituted purine derivatives was briefly investigated.

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“…1′-Homocarbonucleosides with a cyclobutene ring had no significant activity against HIV-1 and HSV-1 [17]. In the series of 2′- or 3′-hydroxymetyl cyclopentane -1′-homocarbanucleosides, a few compounds presented a slight antiviral or anticancer activity [18,19], while 1′,3′-disubstituted cyclopentene analogs [20] or 2′,3′- cis diols [21], were found to be inactive. Other analogs synthesized had low or no antiviral activity [22,23,24], with the exception of the adenine analog [24].…”

Section: Introductionmentioning

confidence: 99%

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

Tănase

Drăghici²,

Hanganu³

et al. 2019

Molecules

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New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC50 (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC50 (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.

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Synthesis of novel carbocyclic nucleosides with a cyclopentenyl ring: Homocarbovir and analogues

Cited by 14 publications

References 11 publications

Synthesis and Biological Activity of Selected Carbocyclic Nucleosides

Synthesis and Biological Activity of Selected Carbocyclic Nucleosides

Synthesis of Carbocyclic Homo-N-Nucleosides from Iridoids

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

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