G. V. Sidorov

Cell Metabolism of Acyclovir Phosphonate Derivatives and Antiherpesvirus Activity of their Combinations with α2-Interferon

The combinational use of acyclovir (ACV) phosphonate esters and α2‐interferon was shown to produce a synergistic effect on inhibition of HSV‐1 replication in Vero cell cultures. Unlike other acyclovir phosphonate derivatives studied earlier, ACV H‐phosphonate is not an ACV prodrug. On penetrating into the cells, it may be directly converted into ACV monophosphate escaping dephosphonylation–phosphorylation steps.

Synthesis of physiologically active tritiated compounds using high specific activity tritiated water

A number of physiologically active compounds—steroid hormones, some phytohormones, carbohydrates and nicotinamide adenine dinucleotide—have been tritiated using high specific activity tritiated water produced by the oxidation of tritium gas on palladium oxide and in the presence of a dry organic solvent. In the process the effect of various variables such as catalyst and solvent have been investigated. The products so obtained had specific activities in the range 3–25 Ci/mmol. Copyright

Synthesis of tritium- and deuterium-labeled isopentenyladenine

The effect of catalysts and temperature on the solid-phase isotope exchange of isopentenyladenine with deuterium and tritium was studied. In the temperature interval 150–170°C, the reaction can be performed selectively, preserving the double bound of the initial compound. The formation of isotopomers was recorded by mass spectrometry. Slightly more than two deuterium atoms are incorporated, on the average, into isopentenyladenine molecule. The efficiency of the isotope exchange increases at the moment of hydrogenation of the initial compound. Deuterium- and tritium-labeled isopentenyladenine and dihydroisopentenyladenine were synthesized. Labeled isopentenyladenine is capable of specific binding with AHK4 cytokinin receptor.

Isotope exchange reactions of trans-zeatin with tritium

Isotope exchange of trans-zeatin with high-activity tritium water and with gaseous tritium in solution, and also the solid-phase catalytic hydrogenation of this compound were studied. The isotope exchange of trans-zeatin with gaseous tritium, both in solution and without a solvent at 160°C and higher temperatures, is accompanied by virtually complete hydrogenation of the starting compound with the formation of tritium-labeled dihydrozeatin. The isotope exchange of trans-zeatin with high-activity tritium water allows preparation of tritium-labeled zeatin in 67% yield and molar activity of 0.68 PBq mol−1. When the solid-phase isotope exchange is performed at 150–155°C, the reaction products contain tritium-labeled trans-zeatin along with the hydrogenation product, dihydrozeatin. At 170°C, the only reaction product is dihydrozeatin. Thus, the selectivity of tritium labeling varies with the temperature of solid-phase catalytic hydrogenation. Below 160°C, the solid-phase reaction can be performed selectively, i.e., with the preservation of the double bond in the starting trans-zeatin. Above 170°C, the selectivity is lost, and the compound is virtually fully hydrogenated to dihydrozeatin.

Synthesis of tritium‐labelled diazines and their analogues

Some 40 diazines have been tritiated to high specific activities using a variety of labelling procedures such as catalytic hydrogen isotope exchange both in solution and the solid state, reduction and hydration. For purine derivatives it is shown that the solid state catalytic isotope exchange reaction is the most effective method. With pyrimidines this reaction is accompanied by a parallel hydration reaction of the 5,6-double bond to form a complex mixture of products. Identification and quantitative estimation of these products has been accomplished in terms of the reaction condition (solvent, nature of catalyst).

Synthesis of tritium-labeled Ganciclovir

The influence of temperature on the solid-phase isotope exchange of Ganciclovir with tritium was studied. Synthesis conditions were found, and tritium-labeled Ganciclovir with the molar radioactivity of 25 Ci mmol−1 (0.925 PBq mol−1) and purity higher than 98% was prepared.

Synthesis of tritium-labeled 5-fluorouracil and 5-fluorocytosine

The effect of various catalysts and temperature on the solid-phase isotope exchange of 5-fluorouracil and 5-fluorocytosine with tritium was studied. The isotope exchange yielding the desired compounds is accompanied by dehalogenation and hydrogenation of the 5,6-double bond of the pyrimidine ring. Performing the reaction at a temperature below 160°C allowed the process to be carried out selectively, i.e., with the preservation of the functional groups and double bond in the starting compound. The yields of various products formed in the reactions of tritium with the above compounds were estimated. Synthesis conditions were found, and tritium-labeled 5-fluorouracil and 5-fluorocytosine were prepared with the molar radioactivity of 0.45 Ci mmol−1 (16.7 TBq mol−1) and 4.4 Ci mmol−1 (0.16 PBq mol−1), respectively, and with the purity exceeding 98%.

Solid-phase catalytic reactions of tritium with carbohydrates: 2. Influence of the support surface area on the solid-phase catalytic hydrogenation of biologically active compounds with tritium

The influence of the support surface area on the yield and specific activity of biologically active compounds prepared by solid-phase catalytic hydrogenation was examined. With an increase in the surface area of the support (barium sulfate), the specific activity of adenine and D-ribose increases, but their yield decreases.

Solid-phase catalytic reactions of tritium with carbohydrates: 4. Mechanism of isomerization of D-glucose in the course of solid-phase catalytic hydrogenation with tritium

The influence exerted on solid-phase catalytic hydrogenation (SCH) of D-glucose with tritium by the temperature varied in the range 90–140°C, platinum group catalysts, solid phase composition, reaction time, and surface area of the support was examined. Fructose and mannose were identified in the reaction products along with labeled glucose. The mechanism of the isomerization of glucose into fructose and mannose in the solid phase under the action of hydrogen spillover was suggested. The glucose isomerization occurs by a complex mechanism analogous to acid-catalyzed keto-enol tautomerization of epimeric sugars in solution, and the active species in SCH of D-glucose with tritium is spillover hydrogen in the form of proton.

Synthesis of tritium-labeled 2′,3′-dideoxy-2′,3′-didehydrothymidine and 3′-azidothymidine-5′-phosphamide

Tritium-labeled 2′,3′-dideoxy-2′,3′-didehydrothymidine and 3′-azidothymidine-5′-phosphamide were prepared by isotope exchange with highly enriched tritium water. Tritium water was prepared by oxidation of high-percentage tritium on PdO. The isotope exchange was performed at 100°C in the dioxane-triethylamine mixed solvent (9: 1 by volume). The molar radioactivities (GBq mol−1) and yields (%) of the products were, respectively, as follows: 2′,3′-dideoxy-2′,3′-didehydrothymidine, 82, 44; 3′-azidothymidine-5′-phosphamide, 200, 71.