Stereospezifische Synthese des Cancerostatikums 5′‐Desoxy‐5‐fluor‐uridin (5‐DFUR) und seiner 5′ ‐deuterierten Derivate

Kiss, Joseph E.; D’Souza, Richard; Koeveringe, J. A. van; Arnold, Wolf

doi:10.1002/hlca.19820650525

Cited by 33 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the higher temperatures allowed by toluene or p -xylene (Table , entries 4 and 5), the reaction produces a small amount of the α-isomer (possibly 9-α), consistent with previous observations for trimethylsilyl triflate catalyzed glycosylation reactions . Kiss et al also reported that at room temperature, trimethylsilyl triflate catalyzed β to α epimerization of uridine derivatives over the course of a week . The guanosine derivative 5 may epimerize more rapidly at the higher reaction temperatures used in our study.…”

supporting

confidence: 92%

Efficient Synthesis of 2‘-C-β-Methylguanosine

Piccirilli²

2006

J. Org. Chem.

View full text Add to dashboard Cite

2'-beta-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2'-C-beta-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-d-ribofuranose (1) and N2-acetylguanine, we obtained the title compound in two steps (78% overall yield) with high stereoselectivity (beta/alpha > 99:1) and high regioselectivity (N9/N7 > 99:1). Extension of this strategy to the classic synthesis of guanosine also resulted in high stereoselectivity (beta/alpha = 99:1) and improved regioselectivity (N9/N7 = 97:3).

show abstract

supporting

confidence: 92%

Efficient Synthesis of 2‘-C-β-Methylguanosine

Piccirilli²

2006

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…The self-anomerization of nucleosides and nucleotides catalyzed by TMSBr has not been described yet and appears to be a very interesting alternative to the previously reported procedures. [43][44][45][46][47][48][49] The transformation occurs in very mild conditions that can be paralleled to those reported by Kiss et al 45 and Yamaguchi et al 46 The first authors mentioned anomerization of a 5′-deoxy-5fluorouridine analogue catalyzed by trimethylsilyl trifluoromethanesulfonate (TMS-OTf). The transformation however is described to be extremely slow at room temperature, and only a minute amount of the R-anomer (2%) was formed over a week.…”

Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 77%

Synthesis of Polyphosphorylated AZT Derivatives for the Development of Specific Enzyme Immunoassays

et al. 1999

View full text Add to dashboard Cite

The synthesis of a series of analogues of the different polyphosphorylated metabolites of AZT has been carried out. The compounds were designed in order to raise specific antibodies for the development of highly sensitive titration kits for the intracellular metabolites of AZT. The pyrophosphate moiety in AZT-DP and AZT-TP analogues is mimicked by the methylene bisphosphonate group to provide in vivo stability of the compounds. An ω-amino linker was introduced at the N 3 position on the base to allow the further anchoring of the compounds to a carrier protein before immunization, tentitatively focusing the specificity of the immune response toward the phosphate mimic moiety and the nonnatural sugar.

show abstract

“…The same authors, by this method, prepared also the 5 0 -monodeutero and the 5 0 ,5 0 -dideutero derivatives and the a-anomer of doxifluridine. 107 Scheme 55…”

Section: Doxifluridinementioning

confidence: 99%

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

Ferraboschi

Ciceri

Grisenti

2017

Organic Preparations and Procedures International

View full text Add to dashboard Cite

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...

show abstract

Stereospezifische Synthese des Cancerostatikums 5′‐Desoxy‐5‐fluor‐uridin (5‐DFUR) und seiner 5′ ‐deuterierten Derivate

Cited by 33 publications

References 21 publications

Efficient Synthesis of 2‘-C-β-Methylguanosine

Efficient Synthesis of 2‘-C-β-Methylguanosine

Synthesis of Polyphosphorylated AZT Derivatives for the Development of Specific Enzyme Immunoassays

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

Contact Info

Product

Resources

About