1-(2,3-Dideoxy-<i>erythro</i>-β-<scp>D</scp>-hexopyranosyl)cytosine: an example of the conformational and stacking properties of pyranosyl pyrimidine nucleosides. A crystallographic and computational approach

Winter, Hans De; Ranter, C. J. De; Blaton, N. M.; Peeters, O. M.; Herdewijn, Piet

doi:10.1107/s0108768191010546

Cited by 12 publications

(2 citation statements)

References 15 publications

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“…1.5-Anhydro-4,6-0-benzylidene-3-deoxy-2-O-(p-tolylsulfonyl)-D-riho-hexitol (10). (A) Tosylated sugar 8 (11.22 g, 27.6 mmol) and 23.60 g (193 mmol) of 4-(dimethylamino)pyridine (DMAP) were dissolved in 400 mL of dry CH2C12.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Verheggen

Toppet²,

Snoeck³

et al. 1993

J. Med. Chem.

152

102

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The synthesis of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol 4b at a concentration of 0.07 microgram/mL. This activity must be dependent on a specific phosphorylation by the virus-encoded thymidine kinase (TK), since compound 4b was inactive against TK-deficient mutants of HSV-1. The corresponding cytosine 4c and guanine 4e analogues showed activity against HSV-1, HSV-2, and other herpes viruses (i.e. cytomegalovirus, varicella-zoster virus) at concentrations well below the cytotoxicity threshold (2 and 20 micrograms/mL, respectively). At these concentrations, compounds 4c and 4e proved also inhibitory to the growth of human T-cells (i.e. MT-4, CEM, MOLT-4).

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Section: Methodsmentioning

confidence: 99%

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Verheggen

Toppet²,

Snoeck³

et al. 1993

J. Med. Chem.

152

102

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“…The benzylidene moiety was hydrolyzed by 80% acetic acid at 70 °C. Likewise, N3benzoyl-5-fluorouracil (14), A^-benzoyl-5-iodouracil (15), and IV^benzoyl-S-ethyluracil (16) were reacted with 12 to afford 2, 3, and 4 in 62%, 50%, and 44% overall yield, respectively.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides

Verheggen¹,

Aerschot²,

Meervelt³

et al. 1995

J. Med. Chem.

116

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In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2- (5-iodouracil-1-yl)-D-arabino-hexitol, a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation.

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Nucleic Acids with a Six‐Membered ‘Carbohydrate’ Mimic in the Backbone

Herdewijn

2010

Chemistry & Biodiversity

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Starting from pyranose nucleic acids, several series of modified nucleic acids with a six-membered carbohydrate moiety (mimic) have been synthesized and analyzed over a period of 20 years, and this work is summarized here. The process starts with structural and conformational considerations, followed by synthetic efforts and a structural analysis, and ends up with a biological confirmation of the concept, demonstrating that these modified nucleic acids represent very valuable tools in chemistry and biology.

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1-(2,3-Dideoxy-erythro-β-D-hexopyranosyl)cytosine: an example of the conformational and stacking properties of pyranosyl pyrimidine nucleosides. A crystallographic and computational approach

Cited by 12 publications

References 15 publications

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides

Nucleic Acids with a Six‐Membered ‘Carbohydrate’ Mimic in the Backbone

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