Straightforward Pyrimidine Ring Construction: A Versatile Tool for the Synthesis of Nucleobase and Nucleoside Analogues

Robin, Aélig; Julienne, Karine; Meslin, J. C.; Deniaud, David

doi:10.1002/ejoc.200500556

Cited by 20 publications

(7 citation statements)

References 21 publications

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“…The strategy to access these new compounds was based on the application of different types of phosphonate carbanions [Wadsworth–Horner–Emmons (WHE) reagents] to N 1 ‐allyl‐ and N 3 ‐allyl‐2‐thiouracils, under phase‐transfer catalysis conditions. The known N ‐allyl‐2‐thiouracils 3 and 4 were synthesized by condensation of N ‐allylthiourea with β‐ketoacetal in the presence of sodium ethoxide or H 2 SO 4 as a condensating agent . Compounds 3 and 4 may undergo double bond migrations forming isomerizes species derived from A B .…”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing FusedN,S-Heterocyclic Phosphor Esters

Abdou

Kamel

Khidre

2014

J. Heterocyclic Chem.

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Reactions of unsaturated and saturated Wadsworth–Horner–Emmons reactants with N1‐ and N3‐allyl‐2‐thiouracils, under phase‐transfer catalysis conditions, resulted in the respective N‐bridged thiazolo‐, pyrrolo‐, and thiazino‐phosphor esters. Products were obtained via the regioselective attack of the Wadsworth–Horner–Emmons reagent on the allylic‐1′‐C in tandem of double bond migration processes, followed by a series of transformations. Synthesis of pyrimidin‐1(2H, or 6H)‐yl)but‐1‐ene‐1,1‐diyldiphosphonates was also described. On the basis of the prediction results (PASS program, Moscow, Russia; free available internet version of PASS 2009.1: http://http://www.ibmc.msk.ru/PASS), we further estimated the antioxidant and antidiabetic activities of the synthesized compounds. The results showed that all compounds cause moderate to good antidiabetic activities. However, the thiazolophosphonates exhibited the highest inhibitory antioxidant activity; nevertheless, the diphosphonates manifested the best protective effects against DNA damage induced by bleomycin. Biological testing confirmed the results of computational modeling.

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Section: Resultsmentioning

confidence: 99%

“…All international principles and local regulations concerning the care and use of laboratory animals were considered during the pharmacological screening. The substrates 3 and 4 were prepared according to the reported methods .…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing FusedN,S-Heterocyclic Phosphor Esters

Abdou

Kamel

Khidre

2014

J. Heterocyclic Chem.

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“…Indeed, we have previously published the direct and easy modification of 4-methylsulfanylpyrimidin-2-ones (Scheme 2). 5 Nucleophilic displacements of the sulfanyl group were achieved in good yields with hydrogen sulphide in basic medium or potassium hydroxide in alcoholic medium. Other nucleophiles such as sodium alkoxides or amines were also used with success on pyrimidine-2thiones.…”

Section: Scheme 1 Preparation Of Model Substrate 1 For Methylsulfanylmentioning

confidence: 99%

Concerning the Nucleophilic Displacement of a Methylsulfanyl Group on Substituted Pyrimidinones

Kikelj¹,

Grosjean²,

Meslin³

et al. 2010

Synthesis

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The nucleophilic displacement of a methylsulfanyl group (SMe) at the C2-position on a pyrimidin-4-one scaffold was achieved after oxidation into a methylsulfonyl group (SO 2 Me) using dimethyldioxirane (DMDO), a powerful electrophilic oxygen atom transfer agent. The introduction of amino groups as well as formation of carbon-carbon bonds was thus demonstrated.During the course of our investigations on heterocyclic chemistry, 1,2 we became interested in the nucleophilic displacement of a methylsulfanyl group on a pyrimidinone skeleton. We recently published the synthesis of pyrimidic nucleoside analogues from a glucosyldiazadiene and acylchlorides in a regioselective hetero-cyclocondensation reaction. 3 We are now targeting access to new nucleoside analogues bearing more complex and original heterocyclic bases. Such novel compounds could be generated by further elaboration of the available pyrimidic analogues through the introduction of various substituents on the pyrimidinone ring. It appeared clear that the presence of the methylsulfanyl group on the heterocycle could help achieve this goal.Here, we report on studies undertaken with the model substrate 1 into the generation of a nonglycosidic series. Pyrimidinone 1 was prepared according to our heterocyclocondensation methodology by employing an activated 1,3-diazabutadienic building block (Scheme 1). 4 The heterodiene, which was obtained in three steps from phenylthiourea in quantitative yield, was condensed with phenylacetyl chloride in the presence of triethylamine to afford compound 1 in 90% yield. Scheme 1 Preparation of model substrate 1 for methylsulfanyl group displacement studiesThe methylsulfanyl substituent is located at the C2-position of the pyrimidin-4-one 1. It is worth noting the high difference in reactivity compared to the case of a C4-positioned substituent on a pyrimidin-2-one scaffold. Indeed, we have previously published the direct and easy modification of 4-methylsulfanylpyrimidin-2-ones (Scheme 2). 5 Nucleophilic displacements of the sulfanyl group were achieved in good yields with hydrogen sulphide in basic medium or potassium hydroxide in alcoholic medium. Other nucleophiles such as sodium alkoxides or amines were also used with success on pyrimidine-2-thiones. However, these substitution reactions were limited to heteroatomic nucleophiles. Indeed, attempts at the introduction of a carbon-carbon bond failed.Scheme 2 Modulation of 4-methylsulfanylpyrimidin(e)-2-(thi)ones by direct substitution of the sulfanyl group Additionally, we hoped to effect substitution of the C2-sulfanyl of pyrimidin-4-one 1. We were therefore disappointed to observe the very weak reactivity of this substrate, particularly towards nitrogenous nucleophiles. Only the hydroxide anion could, under severe conditions (high temperatures and extended reaction times), generate the corresponding carbonyl derivative 2 through substitution and prototropic equilibrium. This difficulty is hardly mentioned in the literature, even for reactions at the C2-position on pyrimidine r...

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“…Furthermore, we have also published the synthesis of different non‐natural N ‐glycosyl pyrimidines. Furanosides, pyranosides, as well as disaccharides were isolated . Perbenzoylated ribofuranoside 2 and peracetylated glucopyranoside 3 represent this class of targeted and isolated pyrimidines (Figure ).…”

Section: Introductionmentioning

confidence: 99%

“…Furanosides, pyranosides, as well as disaccharides were isolated. [11][12][13] Perbenzoylated ribofuranoside 2 and peracetylated glucopyranoside 3 represent this class of targeted and isolated pyrimidines ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Approach to Artificial Nucleosides from Glycoside Isothiocyanates: Synthesis of Original N‐Glycosylated Heterostructures by Cyclocondensation Reactions

et al. 2019

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Unusual purine nucleoside analogues were synthesized, using the well‐tried methodology in heterocyclic chemistry. This result expands the scope of accessible N‐glycosylated heterocyclic structures. Pyrimidine, and bicyclic pyrimido[1,2‐a]pyrimidine nucleoside analogues were prepared from common glycoside isothiocyanate precursors. Key cyclization steps were all based on a cyclocondensation reaction involving an activated heterodienic chain. Finally, thirteen pyrimido[1.2‐a]pyrimidine nucleoside analogues 13 a‐m were synthesized with a 30% yield on average, over 8 or 9 steps from one of the isothiocyanates 4 a‐c. These elaborated targets were fully characterized.

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Straightforward Pyrimidine Ring Construction: A Versatile Tool for the Synthesis of Nucleobase and Nucleoside Analogues

Cited by 20 publications

References 21 publications

Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing FusedN,S-Heterocyclic Phosphor Esters

Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing FusedN,S-Heterocyclic Phosphor Esters

Concerning the Nucleophilic Displacement of a Methylsulfanyl Group on Substituted Pyrimidinones

Approach to Artificial Nucleosides from Glycoside Isothiocyanates: Synthesis of Original N‐Glycosylated Heterostructures by Cyclocondensation Reactions

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