A concise synthesis of 3-fluoro-5-thio-xylo- and glucopyranoses, useful precursors towards their corresponding pyranonucleoside derivatives

Tsoukala, Evangelia; Manta, Stella; Tzioumaki, Niki; Agelis, George; Komiotis, Dimitri

doi:10.1016/j.carres.2008.02.004

Cited by 4 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deprotection of nucleosides 2a-e in methanolic ammonia gave the fully unprotected derivatives 3a-c,f,g, while the base protected benzoylated derivatives 3d,e were obtained when 2d,e were treated with NaOH-ethanol-pyridine [10,11,14]. Subsequently, the tosylated derivatives 4a-e, after treatment with potassium thioacetate in hot N,N-dimethylformamide (DMF) [36][37][38], were converted into the corresponding thioacetates, 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6thio-b-D-glucopyranosyl)thymine (5a), 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)uracil (5b), 1-(2,4di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)5-fluorouracil (5c), 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3fluoro-6-thio-b-D-glucopyranosyl)-N 4 -benzoyl cytosine (5d) and 9-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)-N 6 -benzoyl adenine (5e), respectively. Subsequently, the tosylated derivatives 4a-e, after treatment with potassium thioacetate in hot N,N-dimethylformamide (DMF) [36][37][38], were converted into the corresponding thioacetates, 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6thio-b-D-glucopyranosyl)thymine (5a), 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)uracil (5b), 1-(2,4di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)5-fluorouracil (5c), 1-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3fluoro-6-thio-b-D-glucopyranosyl)-N 4 -benzoyl cytosine (5d) and 9-(2,4-di-O-acetyl-6-S-acetyl-3-deoxy-3-fluoro-6-thio-b-D-glucopyranosyl)-N 6 -benzoyl adenine (5e), respectively.…”

Section: Synthesismentioning

confidence: 99%

Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Tsoukala

Tzioumaki

Manta

et al. 2010

Bioorganic Chemistry

Self Cite

View full text Add to dashboard Cite

The 3-deoxy-3-fluoro-6-S-(2-S-pyridyl)-6-thio-β-D-glucopyranosyl nucleoside analogs 7 were prepared via two facile synthetic routes. Their precursors, 3-fluoro-6-thio-glucopyranosyl nucleosides 5a-e, were obtained by the sequence of deacetylation of 3-deoxy-3-fluoro-β-D-glucopyranosyl nucleosides 2a-e, selective tosylation of the primary OH of 3 and finally treatment with potassium thioacetate. The desired thiolpyridine protected analogs 7a-c,f,g were obtained by the sequence of deacetylation of 5a-c followed by thiopyridinylation and/or condensation of the corresponding heterocyclic bases with the newly synthesized peracetylated 6-S-(2-S-pyridyl) sugar precursor 13, which was obtained via a novel synthetic route from glycosyl donor 12. None of the compounds 6 and 7 showed antiviral activity, but the 5-fluorouracil derivative 7c and particularly the uracil derivative 7b were endowed with an interesting and selective cytostatic action against a variety of murine and human tumor cell cultures.

show abstract

Section: Synthesismentioning

confidence: 99%

Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Tsoukala

Tzioumaki

Manta

et al. 2010

Bioorganic Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Attachment of fluorine atoms on the sugar and heterocyclic moieties of such analogues is known to be of advantage both for an improved activity, higher bioavailability as well as for causing a retarded catabolism of several drugs [6][7][8][9]. Therefore, specific fluorination at the 2 0 -and/or 3 0 -position of the sugar moiety of the nucleosides has been studied in the pursuit of safe, effective and chemically stable antiviral agents [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4,6-dideoxy-3-fluoro-2-keto-β-d-glucopyranosyl analogues of 5-fluorouracil, N6-benzoyl adenine, uracil, thymine, N4-benzoyl cytosine and evaluation of their antitumor activities

Manta

Tsoukala

Tzioumaki

et al. 2010

Bioorganic Chemistry

Self Cite

View full text Add to dashboard Cite

The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-d-glucopyranosyl nucleosides of 5-fluorouracil (6a), N(6)-benzoyl adenine (6b), uracil (6c), thymine (6d) and N(4)-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regioselective 2'-O-deacylation afforded the partially acetylated dideoxynucleoside analogues of 5-fluorouracil (5a) and N(6)-benzoyl adenine (5b), respectively. Direct oxidation of the free hydroxyl group at the 2'-position of 5a,b, with simultaneous elimination reaction of the beta-acetoxyl group, afforded the desired unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-D-glucopyranosyl derivatives 6a,b. Compounds 1c-e were used as starting materials for the synthesis of the dideoxy unsaturated carbonyl nucleosides of uracil (6c), thymine (6d) and N(4)-benzoyl cytosine (6e). Similarly a protection-selective deprotection sequence followed by oxidation of the free hydroxyl group at the 2'-position of the dideoxy benzoylated analogues 9c-e with simultaneous elimination reaction of the beta-benzoyl group, gave the desired nucleosides 6c-e. None of the compounds was inhibitory to a broad spectrum of DNA and RNA viruses at subtoxic concentrations. The 5-fluorouracil derivative 6a was more cytostatic (50% inhibitory concentration ranging between 0.2 and 12 microM) than the other compounds.

show abstract

Keto-fluorothiopyranosyl nucleosides: a convenient synthesis of 2- and 4-keto-3-fluoro-5-thioxylopyranosyl thymine analogs

Tsoukala¹,

Manta²,

Tzioumaki³

et al. 2011

Carbohydrate Research

View full text Add to dashboard Cite

A concise synthesis of 3-fluoro-5-thio-xylo- and glucopyranoses, useful precursors towards their corresponding pyranonucleoside derivatives

Cited by 4 publications

References 29 publications

Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Synthesis of 4,6-dideoxy-3-fluoro-2-keto-β-d-glucopyranosyl analogues of 5-fluorouracil, N6-benzoyl adenine, uracil, thymine, N4-benzoyl cytosine and evaluation of their antitumor activities

Keto-fluorothiopyranosyl nucleosides: a convenient synthesis of 2- and 4-keto-3-fluoro-5-thioxylopyranosyl thymine analogs

Contact Info

Product

Resources

About