Preparation of 5‐fluorouracil‐6‐<sup>3</sup>H of high specific activity

Filip, J; Vyšata, František

doi:10.1002/jlcr.2590050402

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The relative values of the observed first-order rate constants for decarboxylation of 1 at 206°in sulfolane, tetraglyme, and decarboxylation at lower temperatures than the iV-methyi or unsubstituted acids. 23 In those cases, the overall rate is apparently influenced by inductive stabilization of negative charge either in the carboxylate, in the zwitterion, or in the transition state for loss of carbon dioxide.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of decarboxylation of 1,3-dimethylorotic acid. A model for orotidine 5'-phosphate decarboxylase

Beak¹,

Siegel²

1976

J. Am. Chem. Soc.

120

133

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with stirring, under nitrogen at 5 OC, 0.25 ml of methyl fluorosulfonate (3.1 mmol) over a period of 15 min. The oily precipitate was stirred at 4 OC overnight to give a white solid, which was washed repeatedly with dry ether and dried under vacuum over P205. The slightly hydroscopic material decomposed in the range 60-80 OC. The NMR spectrum in CD3CN gave the following peaks relative to Me&: 6 9.1 ( 1 H, s), 7.9-7.5 ( 7 H, m), and 4.0 (3 H, s). This material was used in the kinetic studies without further purification.Kinetic Measurements, Pseudo-first-order rate constants were determined either spectrophotometrically at 260 nm using a Cary 14 spectrophotometer or by a pH stat method using a Radiometer apparatus which included a TTT60 titrator, PHM62 pH meter, ABU 12T buret, and a REC61 servograph. Stock solutions of 3 were prepared in acetonitrile and were stable for weeks when stored at -15 "C. Stock solutions of 4 were prepared in acetonitrile and used the same day. Stock solutions of 2 were prepared in MezSO and were used within 2 h. No solvent was found for 2 which afforded solutions stable for more than 2 h. Typically, 10-50 p1 of stock solution was used to initiate the reaction. In many pH-stat runs, 2 was added as a solid directly to the reaction vessel. Results using this technique compared well with results using fresh stock Me2SO solutions. The concentration of substrates was approximately 3 X M for the pH-stat runs and about 2.5 X M for the spectrophotometric runs. The pseudofirst-order rate constants were fit to the appropriate rate expression using a nonlinear least-squares computer program.Abstract: The decarboxylation of 1,3-dimethylorotic acid (1) is shown to proceed by separate pH-determined pathways in sulfolane at 180-220 OC. Although a process involving ionization of 1 is the major pathway in the presence of excess base, decarboxylation is initiated by zwitterion formation in the neutral solvent. Measurements of the rate of loss of carbon dioxide from 6-carboxy-2,4-dimethoxypyrimidine ( 5 ) and 1 -methyl-2,4-dimethoxypyrimidinium-6-carboxylate betaine (7) are used to estimate the equilibrium and rate constants for the zwitterionic pathway. Comparison of the rate constant for decarboxylation of 7 with k,,, for orotidine 5'-phosphate decarboxylase shows that the biological catalysis can be satisfactorily accounted for if the enzyme provides a site which displaces the equilibrium in favor of the zwitterionic form of orotidylic acid. It is also noted that the inhibitor 6-azauridine monophosphate, which has a greater affinity for the enzyme than does the substrate, provides a partial model for the intermediate formed on loss of carbon dioxide from the zwitterion.

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Section: Discussionmentioning

confidence: 99%

Mechanism of decarboxylation of 1,3-dimethylorotic acid. A model for orotidine 5'-phosphate decarboxylase

Beak¹,

Siegel²

1976

J. Am. Chem. Soc.

120

133

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“…166 Electrolytic reduction of 5-bromouracil in tritiated water (mercury cathode, platinum anode) yielded [5-3 H]uracil. 167 Decarboxylation of 5-substituted derivatives of orotic acid labelled with tritium in the carboxyl group produced [6-3 H]thymine 168 from 5-methylorotic acid, 5-fluoro[6-3 H]uracil 169 and 5bromouracil 170 from the corresponding 5-halogeno-derivatives of orotic acid. The molar radioactivity of these products did not exceed 1 Ci mmol 71 .…”

Section: Other Methods Of Tritium Labellingmentioning

confidence: 99%

Synthesis of tritium-labelled biologically important diazines

Sidorov¹,

Myasoedov²

1999

Russ. Chem. Rev.

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In a series of publications we presented a solution of the time-dependent Schrodinger equation for collisions between one-electron ions and atoms by an expansion in terms of two-centre wavefunctions of the Hylleraas type. In this contribution we present differential cross sections for direct and electron exchange processes in proton-hydrogen collisions at 1 and 2 keV. The scattering angle dependence as well as the energy dependence of the related charge exchange probability is studied and compared with competing theoretical approaches and experiment.

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