Unsaturated fluoro-ketopyranosyl nucleosides: Synthesis and biological evaluation of 3-fluoro-4-keto-β-d-glucopyranosyl derivatives of N4-benzoyl cytosine and N6-benzoyl adenine

Manta, Stella; Agelis, George; Botić, Tanja; Cencič, Avrelija; Komiotis, Dimitri

doi:10.1016/j.ejmech.2007.04.001

Cited by 29 publications

(36 citation statements)

References 71 publications

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“…In an attempt to find new antitumor and antiviral agents, we have previously synthesized a series of unsaturated keto [23,24] as well as exomethylene pyranonucleo-side analogues [25,26], which proved to be efficient as tumor cell growth inhibitors and showed to have a promising potential in combating rotaviral infections. Our studies demonstrated that the presence of a primary hydroxyl group did not seem to be a prerequisite for biological activity, contrary to the 69-protected analogues that exhibited the most promising cytotoxic and antiviral properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Tzioumaki¹,

Tsoukala²,

Manta³

et al. 2009

Archiv der Pharmazie

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This report describes the synthesis of unsaturated exomethylene lyxopyranonucleoside analogues as potential biologically active agents. Commercially available 1,2,3,4-tetra-O-acetyl-alpha-D-lyxopyranose 1 was condensed with silylated thymine and uracil, respectively, deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-alpha-D-lyxopyranosyl)thymine 4a and 1-(2,3-O-isopropylidene-alpha-D-lyxopyranosyl)uracil 4b. The new derivatives 1-(2,3,4-trideoxy-4-methylene-alpha-pent-2-enopyranosyl)thymine 8a and 1-(2,3,4-trideoxy-4-methylene-alpha-pent-2-enopyranosyl)uracil 8b were prepared via two different key intermediates, 7a, b and 13a, b in order to elucidate the influence of 2',3'-unsaturation and to clarify the difference between the keto and exomethylene group on the biological activity of the target molecules. Compounds 7a, b, 8a, b, and 13a, b were evaluated for their antiviral and cytostatic activity using several virus strains and cell lines. Whereas no marked antiviral activity was noticed, 13a and 13b showed a cytostatic activity that ranged between 7 and 23 muM for 13a and 26 and 38 muM for 13b against murine leukemia L1210, human lymphocyte Molt4/C8 and CEM cells, and human breast carcinoma MCF7 cells.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Tzioumaki¹,

Tsoukala²,

Manta³

et al. 2009

Archiv der Pharmazie

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“…371 Isopropylidination of 1059 and subsequent acetylation of the remaining hydroxyl group gave the acetyl derivative 1063 in 71% yield, which was subjected to deisopropylidination with TFA and selective protection with a trityl group to yield the alcohol 1064. PDC oxidation followed by in situ b-elimination provided the unsaturated 3-fluoro-4-keto-b-D-glucopyranosyl derivative 1065 in 75% yield.…”

Section: Monofluorinated or Monofluoromethylated Cyclobutane Nucleosidesmentioning

confidence: 99%

Recent advances in the synthesis of fluorinated nucleosides

Qiu¹,

Xu²,

Qing³

2010

Tetrahedron

144

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“…This conjugation proved to be once again a prerequisite for biological activity. [21][22][23][24][25][26][27][28] It appears that the unsaturated keto system might function as an acceptor in a Michael-addition type mechanism. 27 1.…”

Section: Introductionmentioning

confidence: 99%

“…In our continuing efforts to investigate new antiviral and antitumor agents, we have previously synthesized various unsaturated keto [21][22][23][24] or exomethylene nucleosides. [25][26][27] These uncommon pyranonucleosides proved to have a promising potential in combating rotaviral infections and exhibited cytostatic activity against various cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Efficient synthesis of exomethylene- and keto-exomethylene-d-glucopyranosyl nucleoside analogs as potential cytotoxic agents

Tzioumaki

Tsoukala

Manta

et al. 2011

Carbohydrate Research

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A novel series of exomethylene- and keto-exomethylene-d-glucopyranonucleosides with thymine, uracil, and 5-fluorouracil as heterocyclic bases have been designed and synthesized. Wittig condensation of the 3-keto glucoside 1 gave the corresponding 1,2:5,6-di-O-isopropylidene-3-deoxy-3-methylene-d-glucofuranose (2), which after hydrolysis and acetylation led to the precursor 1,2,4,6-tetra-O-acetyl-3-deoxy-3-methylene-d-glucopyranose (4). Compound 4 was condensed with silylated thymine, uracil, and 5-fluorouracil, respectively, deacetylated and acetalated to afford 1-(3'-deoxy-4',6'-O-isopropylidene-3'-methylene-β-d-glucopyranosyl)pyrimidines 7a-c. Oxidation of the free hydroxyl group in the 2'-position of the sugar moiety led to the formation of the labile 1-(3'-deoxy-4',6'-O-isopropylidene-3'-methylene-β-d-glucopyranosyl-2'-ulose)pyrimidines 8a-c. Finally, deisopropylidenation of the resulted derivatives 8a-c afforded the diol nucleosides 9a-c. The target keto-exomethylene analogs 9a-c were more cytostatic against a variety of tumor cell lines than the corresponding saturated-hydroxy-exomethylene derivatives 6. In particular, the 5-fluorouracil derivative 9c was highly cytostatic at an IC(50) (50% inhibitory concentration) ranging between 0.56 and 9.4 microg/mL, which was comparable to the free parental 5-fluorouracil base.

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Unsaturated fluoro-ketopyranosyl nucleosides: Synthesis and biological evaluation of 3-fluoro-4-keto-β-d-glucopyranosyl derivatives of N4-benzoyl cytosine and N6-benzoyl adenine

Cited by 29 publications

References 71 publications

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Recent advances in the synthesis of fluorinated nucleosides

Efficient synthesis of exomethylene- and keto-exomethylene-d-glucopyranosyl nucleoside analogs as potential cytotoxic agents

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