γ-Radiolysis of 1-Substituted 5-Fluorouracil Derivatives

Kuroda, Tokuyuki; Hisamura, Koji; Matsukuma, I.; Nishikawa, Hiroshi; Nakamizo, Nobuhiro

doi:10.1246/bcsj.62.674

Cited by 7 publications

(2 citation statements)

References 8 publications

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“…From 4-methoxycarbonylphenyl 2-tetrahydropyranyl ether ( 8t , 0.236 g, 1 mmol); stirred for 1 h at rt; white solid; yield: 0.130 g (85%); mp 124–126 °C; R f = 0.45 (PE/EA 3:1). 1 H NMR (400 MHz, CDCl 3 ) δ 7.96 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.67 (br s, 1H), 3.91 (s, 3H).…”

Section: Methodsmentioning

confidence: 99%

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal

et al. 2020

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Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.

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Section: Methodsmentioning

confidence: 99%

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal

et al. 2020

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“…The concept of "radioinduced drug" proposed for cancer therapy is also noteworthy: 5-FU derivatives variously substituted at the 1-position were prepared and the release of the antitumor drug was observed upon g-irradiation. 49 5-FU dimer 55 50 and 5-fluoro-1-(2 0 -oxocycloalkyl)uracil 56 51 released 5-FU 1 by radiation activation under hypoxic conditions (Scheme 26).…”

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confidence: 99%

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

Ferraboschi

Ciceri

Grisenti

2017

Organic Preparations and Procedures International

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5-Fluorouracil35 Interest in the fluoropyrimidines stemmed from studies of the metabolism of uracil in rat hepatoma cells. The observation that these cells utilize uracil more avidly than normal rat intestinal mucosa prompted the preparation of fluorinated pyrimidines in order to improve disruption of tumor DNA biosynthesis. 3 In 1957 5-fluorouracil (5-FU) 1 was synthesized by Heidelberger et al., 4 with the aim of 40 blocking metabolism in malignant cells. The replacement of a hydrogen atom at C-5 by the fluorine atom modifies the interaction with the active sites of enzymes involved in metabolism. This antimetabolite, although toxic, is still one of the most widely used agents against solid tumors. Its action is due to two different mechanisms: 5 after penetration into the cell, 5-FU 1 is transformed into the 5-fluorouridine triphosphate that mimics UTP, is recognized by RNA 45 polymerase and consequently incorporated into RNA. The most significant action, however, is due to the 5-FU conversion into 5-fluoro-2 0 -deoxyuridine (FdUMP) 2, a known inhibitor of thymidylate synthetase (TS), a key enzyme in the DNA synthesis. 6,7 TS, in the presence of methylene tetrahydrofolate and deoxyuridine monophosphate (dUMP) 3 forms a ternary complex that catalyzes the substitution of 5-H uracil with a methyl group, affording thymine. If FdUMP 50 2 is present, the above ternary complex is not able to carry out this reaction, due to the presence of fluorine in the 5-position: the formation of TMP 4 (2 0 -deoxythymidine 5 0 -monophosphate), the only nucleotide precursor specific to DNA, is, therefore, blocked (Scheme 1), decreasing the availability of TTP (2 0 -deoxythymidine 5 0 -triphosphate) for DNA synthesis.Scheme 1 2 Ferraboschi, Ciceri, and GrisentiLater two additional mechanisms were proposed for 5-FU 1 antitumor activity: the 55 incorporation of 5-FU into DNA and the alteration of the membrane function of 5-FU 1 treated cells. Recent studies indicate that the TS-direct mechanism predominates when 1 is administered at low doses for a prolonged time, whereas the RNA-mediated process is more active following a bolus administration. 8-10 Synthesis of 5-FU 1, by construction of the pyrimidine ring, was first realized by Hei-60 delberger et al. in 1957 4,11,12 by reaction of a thiourea derivative 5 with the enolate of ethyl a-fluoro, a-formyl acetate 6 which, in turn, was obtained from methyl formate and ethyl fluoroacetate (Scheme 2). Depending on the chosen a-fluoro-b-ketoester the method is also applicable to the synthesis of other 5-fluoropyrimidines.An alternative method for the total synthesis is the direct fluorination of the pyrimi-65 dine ring of compound 7 by means of trifluoromethyl hypofluorite (CF 3 OF) 13 proposed by Robins in 1971. In the case of CF 3 OF in methanol/fluorotrichloromethane an intermediate was formed that, after treatment with triethylamine, afforded 5-FU 1 in 84% yield. 13 If the reaction was carried out with CF 3 OF in trifluoroacetic acid 1 was directly isolated in 85% yield. 14 The meth...

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ChemInform Abstract: γ‐Radiolysis of 1‐Substituted 5‐Fluorouracil Derivatives.

et al. 1989

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ChemInform Abstract A new concept, "Radiation-Induced Drug" (RID), is proposed as a novel type of drugs for cancer therapy. The concept involves a drug, itself pharmaceutically inactive both for cancer and normal cells, which upon γ-irradiation produces an active drug specifically for cancer cells. 5-Fluorouracil (Ia) is chosen as a base-active drug of the RID concept; therefore a variety of 25 derivatives substituted at the 1-position are prepared by common methods and their γ-radiolyses in aqueous solutions studied. The compounds having sulfonyl and thioureido groups such as (Ib) produce efficiently (Ia).

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γ-Radiolysis of 1-Substituted 5-Fluorouracil Derivatives

Cited by 7 publications

References 8 publications

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal

Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N,N-Dimethylformamide Dimethyl Acetal

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

ChemInform Abstract: γ‐Radiolysis of 1‐Substituted 5‐Fluorouracil Derivatives.

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