Preparation of 6-methyluridine, 6-ethyluridine, and 2'-deoxy-6-ethyluridine

Holý, A.

doi:10.1135/cccc19743374

Cited by 10 publications

(7 citation statements)

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“…1- β - d -Ribofuranosyl-6-ethyluracil (43). This was prepared as described by Holy: 23 mp 115−118 °C (lit . mp 119−121 °C); TLC (silica gel) R f (B) 0.44; UV spectra as for 5 .…”

Section: Methodsmentioning

confidence: 99%

“…24 5-Fluoro-2-methoxy-6-methyluracil (25). To a solution of 1.72 g (10 mmol) of methylpseudoisourea in 30 mL of H2O was added 616 mg (11 mmol) of CaO followed by portionwise addition of a solution of 1.46 mL (10 mmol) of ethyl R-(fluoroacetyl)acetate (23) in 30 mL of EtOH and stirring for 72 h. The mixture was then acidified to pH 3 with HCOOH and filtered through Celite and the latter washed with EtOH, and the combined filtrates were evaporated to dryness. The residue was crystallized from toluene/i-PrOH to yield 995 mg (63%): mp182-185 °C; UV λmax (pH 2) 260 ( 7.7 × 10 3 ), (pH 7) 265 ( 7.42 × 10 3 ), (pH 12) 268 nm ( 7.57 × 10 3 ); TLC (silica gel) Rf (C) 0.64; MS m/z for C6H7FN2O2 calcd 158.049 15, found 158.049 15.…”

Section: -β-D-ribofuranosyl-6-methyluracil (5) Methods Amentioning

confidence: 99%

“…The foregoing high condensation yields were profited from to select conditions for direct synthesis of 6-methyluridine (5) from 4-(methylthio)-6-methyluracil (69) and (ABR), by methanolysis of the product of condensation, followed by hydrolysis of the 4-methylthio group with 1 N TFA, leading to 6-methyluridine (5) in 80% yield. The same procedure with 5,6-dimethyl-4-(ethylthio)uracil ( 14) gave 5,6-dimethyluridine (23) in 60% yield.…”

Section: Chemistrymentioning

confidence: 96%

“…5-Fluoro-6-methyluracil (27) 10 and 6-(trifluoromethyl)uracil (28) 10,11 were prepared from the appropriate β-keto esters: ethyl R-(fluoroacetyl)acetate (23) and ethyl (trifluoroacetyl)acetate (24), as shown in Scheme 4, using the procedure hitherto applied for preparation of 5,6-dialkyl-and 6-alkyluracils. 12 Reaction of the appropriate β-keto ester in aqueous alcohol with methylpseudoisourea, catalyzed by Ca(OH) 2 , gave 5-fluoro-2-methoxy-6-methyluracil (25) in 63% yield and 2-meth- Treatment of 27 with HMDS/TCS gave 2,4-bis-O-(trimethylsilyl)-5-fluoro-6-methyluracil (29), which was condensed with ABR in MeCN (Scheme 5) in the presence of 1.1 equiv of TMSOTfl to give a mixture of blocked isomers consisting of 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluoro-6-methyluracil (30; 45%), the corresponding 3-isomer 31 (21%), and the 1,3-disubstituted analogue 32 (20%).…”

Section: Chemistrymentioning

confidence: 99%

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6-Substituted and 5,6-Disubstituted Derivatives of Uridine: Stereoselective Synthesis, Interaction with Uridine Phosphorylase, and in Vitro Antitumor Activity

et al. 1996

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Stereoselective procedures are described for the synthesis of 6-alkyluridines by Lewis acid-catalyzed condensation of (a) trimethylsilylated 6-alkyl-4-alkylthiouracils with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (ABR) and (b) trimethylsilylated 6-alkyl-3-benzyluracils with ABR. The 4-methylthio group was subsequently removed with the use of 1 N trifluoroacetic acid and the 3-benzyl group by a new modified procedure with the use of the complex BBr3-THF. Furthermore, 6-(hydroxymethyl)uridine (39) and 5-fluoro-6-(hydroxymethyl)uridine (40) were obtained by sequential oxidation with SeO2 and reduction with tetrabutylammonium borohydride of the 6-methyl group of 6-methyluridine (5) and 5-fluoro-6-methyluridine (35), and their corresponding 6-fluoromethyl congeners 41 and 42 were obtained by DAST treatment of 39 and 40, respectively. For all the foregoing nucleosides in the fixed syn conformation about the glycosyl bond, 1H NMR spectroscopy further demonstrated that the pentose rings exist predominantly in the conformation N (3'-endo). Most of the nucleosides were weak substrates of Escherichia coli pyrimidine nucleoside phosphorylase. Enhanced susceptibility to phosphorolysis was exhibited by two of them, 39 and 41, with 6-CH2OH and 6-CH2F substituents capable of formation of an additional hydrogen bond with the enzyme. The 5-fluoro-6-substituted uridines were the poorest substrates. Cytotoxicities of the nucleosides were examined vs the human tumor cell lines MOLT-3, U-937, K-562, and IM-9, as well as PHA-stimulated human lymphocytes. Two of the analogues, 5-fluoro-6-(fluoromethyl)uridine (42) and 5-fluoro-6-(hydroxymethyl)uridine (40), exhibited cytotoxicities comparable to that of 5-fluorouracil.

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“…1- β - d -Ribofuranosyl-6-ethyluracil (43). This was prepared as described by Holy: 23 mp 115−118 °C (lit . mp 119−121 °C); TLC (silica gel) R f (B) 0.44; UV spectra as for 5 .…”

Section: Methodsmentioning

confidence: 99%

Section: -β-D-ribofuranosyl-6-methyluracil (5) Methods Amentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 96%

Section: Chemistrymentioning

confidence: 99%

See 2 more Smart Citations

6-Substituted and 5,6-Disubstituted Derivatives of Uridine: Stereoselective Synthesis, Interaction with Uridine Phosphorylase, and in Vitro Antitumor Activity

et al. 1996

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“…Compound 11b was prepared by the method described for 11a . The reaction was purified by flash column chromatography (CHCl 3 /MeOH = 9.5:0.5 to 9:1) to give the product ( 11b , foam, 0.4389 g, 91%, R f = 0.18 (CHCl 3 /MeOH = 9:1)): mp 62–72 °C (lit . mp 119–121 °C); 1 H NMR (DMSO- d 6 , 400 MHz) δ 11.25 (s, 1 H), 5.52 (s, 1 H), 5.39 (d, 1 H, J = 3.8 Hz), 5.19 (d, 1 H, J = 5.3 Hz), 4.94 (d, 1 H, J = 6.3 Hz), 4.63 (t, 1 H, J = 5.7 Hz), 4.55 (dd, 1 H, J = 5.2 and 9.6 Hz), 4.07 (dd, 1 H, J = 6.0 and 12.0 Hz), 3.73–3.69 (m, 1 H), 3.63–3.58 (m, 1 H), 3.47–3.41 (m, 1 H), 2.56 (q, 2 H, J = 7.3 Hz), 1.17 (t, 3 H, J = 7.3 Hz); 13 C NMR (DMSO- d 6 , 100 MHz) δ 162.5, 158.3, 150.7, 100.7 (CH), 91.6 (CH), 84.8 (CH), 71.0 (CH), 69.8 (CH), 62.1 (CH 2 ), 25.4 (CH 2 ), 12.4 (CH 3 ); MS (ESI) m / z 295 (100) (M + Na); HRMS (ESI, TOF) calcd for C 11 H 16 N 2 O 6 ·Na (M + Na) 295.0906, found 295.0915.…”

Section: Experimental Sectionmentioning

confidence: 99%

Synthesis of 6-Alkyluridines from 6-Cyanouridine via Zinc(II) Chloride-Catalyzed Nucleophilic Substitution with Alkyl Grignard Reagents

et al. 2013

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6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst to form the corresponding 6-alkyluracils. This methodology is applicable to sugar-protected 6-cyanouridine and 6-cyano-2'-deoxyuridine without the protection at the N(3)-imide and provides a facile and general access to versatile 6-alkyluracil and 6-alkyluridine derivatives.

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Proton magnetic resonance study of nucleosides, nucleotides, and dideoxynucleoside monophosphates containing a syn pyrimidine base

Niemczura¹,

Hruska²,

Sadana³

et al. 1981

Biopolymers

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Proton magnetic resonance data have been obtained for 6‐methyl‐2′‐deoxyuridine (dT*), its 3′‐ and 5′‐monophosphates, and its 3′,5′‐diphosphate, as well as for the corresponding thymine derivatives. The synthesis of the dideoxynucleoside monophosphates—d(TpT), d(T*pT), d(TpT*), and d(T*pT*)—was accomplished, and spectral data were obtained for these four dimers. The data show that the 6‐methyluracil base prefers the syn conformation about the N‐glycosyl bond at the monomer and dimer levels. The presence of the syn base leads to increases in the cis couplings of the sugar ring, J1′2″ and J2′3′, which indicate a trend towards eclipsing of the substituents on the C1′‐C2′ and C2′‐C3′ fragments. This trend is discussed in terms of changes in the pseudorotational parameters which describe the pucker of the ring. The syn base destabilizes the g+ conformer about the C4′‐C5′ bond, leading to a preference for the t conformer in all dT* residues at the monomer and dimer levels. Preliminary work on the formation of cyclobutane‐type photodimers in d(T*pT) and d(T*pT*) is discussed and presented as evidence for the capability of the syn 6‐methyluracil base to form base‐stacked complexes.

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Preparation of 6-methyluridine, 6-ethyluridine, and 2'-deoxy-6-ethyluridine

Cited by 10 publications

References 0 publications

6-Substituted and 5,6-Disubstituted Derivatives of Uridine: Stereoselective Synthesis, Interaction with Uridine Phosphorylase, and in Vitro Antitumor Activity

6-Substituted and 5,6-Disubstituted Derivatives of Uridine: Stereoselective Synthesis, Interaction with Uridine Phosphorylase, and in Vitro Antitumor Activity

Synthesis of 6-Alkyluridines from 6-Cyanouridine via Zinc(II) Chloride-Catalyzed Nucleophilic Substitution with Alkyl Grignard Reagents

Proton magnetic resonance study of nucleosides, nucleotides, and dideoxynucleoside monophosphates containing a syn pyrimidine base

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