Synthesis of β-Halofurans

Dembiński, Roman; Li, Yan; Gundapuneni, Deepthi; Decker, Alicia C.

doi:10.1007/7081_2011_57

Cited by 8 publications

(5 citation statements)

References 87 publications

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“…An electrophilic cyclization reaction leading to the formation of β -halofuran rings offers a significant synthetic opportunity. 31 , 32 An analogous protocol leads to the formation of 5-halofuropyrimidine nucleosides, which introduces the halogen in a fully regioselective manner. 33 Addressing this so far unresolved synthetic shortcoming in nucleoside chemistry, the extension of the heterocyclic base conjugated system by appending an alkyne at C-5 was sought by combining iodofuropyrimidines with various terminal acetylenes.…”

Section: Introductionmentioning

confidence: 99%

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

Kaczmarek

Twardy

Olson

et al. 2021

European Journal of Medicinal Chemistry

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A novel methodology to access alkynyl nucleoside analogs was elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro . Regiochemistry of the functionalization was achieved with the aid of 5- endo - dig electrophilic halocyclization of acetyl 5- p -tolyl- or 5- p -pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6- p -tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3- d ]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3- d ]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452 to 481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, represent potential tools for fluorescent tagging, studying nucleoside metabolism, 2′-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds showed antiviral activity (EC 50 1.3-13.2 μM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p -pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p -pentylphenyl potency as a pharmacophore.

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Section: Introductionmentioning

confidence: 99%

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

Kaczmarek

Twardy

Olson

et al. 2021

European Journal of Medicinal Chemistry

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“…[7][8][9][10][11] In general, approaches to the synthesis of β-halofurans can be divided into substitution reactions on the furan core and the construction of a furan ring starting from acyclic precursors. 12,13 The later centers on cycloisomerization or cyclocondensation reactions and includes halogenation/ cyclizations, and cyclizations of precursors that contain already introduced halogens. Electrophilic cyclization reactions are particularly attractive since they provide versatile access to different halofurans by treatment of the same starting material with different halogens.…”

Section: Introductionmentioning

confidence: 99%

“…16 So far, preparative access to 3-fluorofurans includes only a few specific methods; the syntheses usually encompass aggressive conditions or poor yields. 12 Only scarce reports provide a preparative route to β,β′fluorohalofurans, which offer an opportunity for further functionalization of fluorofurans. The iodocyclization of gem-difluorohomopropargyl alcohols (2,2-difluoroalk-3-yn-1-ols) can be induced by iodine monochloride in the presence of a base and microwave irradiation.…”

Section: Introductionmentioning

confidence: 99%

“…MS (EI, m/z): 334 (100%, M + ). NMR ( CDCl 3 , δ, ppm): 1 H 7.83-7.77 (m, 2H), 7.56-7.50 (m, 2H), 7.49-7.42 (m, 3H), 7.39 (dd, J = 5.0, 3.0 Hz, 1H), 7.33-7.28 (m, 1H), 7.21-7.15 (m, 3H), 2.39 (s, 3H); 13 C 148.8 (d, J = 255.9 Hz), 146.4 (d, J = 6.0 Hz), 138.6, 135.4 (d, J = 19.6 Hz), 129.6 (d, J = 2.8 Hz), 129.5 (2C), 129.2 (d, J = 5.0 Hz), 129.0 (2C), 128.2, 127.3, 126.4 (2C), 125.9, 124.2 (d, J = 2.1 Hz), 123.8 (d, J = 5.2 Hz, 2C), 110.5 (d, J = 16.1 Hz), 21.6; 66 19 F −164.0.2-[4-Fluoro-2-(4-methylphenyl)-5-phenylfuran-3-yl]pyridine(12)…”

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Room temperature syntheses of entirely diverse substituted β-fluorofurans

Wheeler

Dembiński

2012

Org. Biomol. Chem.

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Synthesis of highly substituted 3-fluorofurans is reported. The sequence began with preparation of tert-butyldimethylsilyl alk-1-en-3-yn-1-yl ethers from 1,4-disubstituted alk-3-yn-1-ones. Subsequent fluorination of alkenynyl silyl ethers with Selectfluor gave 2-fluoroalk-3-yn-1-ones in almost quantitative yield. Subsequent 5-endo-dig cyclizations using chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (5/5 mol%), N-bromo- or N-iodosuccinimide and gold(I) chloride/zinc bromide (5/20 mol%), all at room temperature, provided a facile method for the generation of substituted 3-fluoro-, 3-bromo-4-fluoro-, and 3-fluoro-4-iodofurans in good yields. Also, 2,2-difluoroalk-3-yn-1-ones were prepared by fluorination of alk-3-yn-1-ones under organocatalytic conditions. The structures of (Z)-tert-butyldimethylsilyl but-1-en-3-yn-1-yl ether, 3-bromo-4-fluorofuran, and 3-fluoro-4-(phenylethynyl)furan were confirmed by X-ray crystallography.

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“…A comparable difference is seen between the piperazines BZP (IC 50 value of 161 μM), and TFMPP and mCPP (IC 50 values of 19 μM and 32 μM, respectively). This increase is most likely due to the addition of a halogen moiety on the phenyl ring, as halogens have been reported to enhance binding to target macromolecules (Dembinski et al 2012). However, an increased potency to inhibit wMSR is not seen when comparing amphetamine and 4-FA.…”

Section: Discussionmentioning

confidence: 99%

Hazard characterization of new psychoactive substances

Zwartsen¹

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Chapter 9 | Hazard characterization of synthetic cathinones using viability, monoamine reuptake and neuronal activity assays Chapter 10 | Cardiotoxicity screening of illicit drugs and new psychoactive substances (NPS) in human iPSC-derived cardiomyocytes using microelectrode array (MEA) recordings Part 3 Thesis wrap up Chapter 11 | General discussion, conclusions and main recommendations Appendix I | References Appendix II | Nederlandse samenvatting

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Synthesis of β-Halofurans

Cited by 8 publications

References 87 publications

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups

Room temperature syntheses of entirely diverse substituted β-fluorofurans

Hazard characterization of new psychoactive substances

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