G. G. Kozlova

Synthesis and Antioxidant Activity of Pyrimidine Acyclonucleosides

The initial compounds were 1,3-bis(2-hydroxy-3-chloropropyl)uracil (I, synthesized from uracil and epichlorohydrin) and 1,3-bis(2-hydroxy-3-chloropropyl)-6-methyluracil (II). Upon substituting radicals for chlorine in compounds I and II by reactions with secondary amines, we obtained compounds III – X. Alternatively, compounds IV and VI can be obtained by treating methyluracil II with a fourfold excess of morpholine or piperidine at 120 – 150°C [5]. However, the latter method failed to yield pure acyclonucleosides with dimethylamine and diethylamine substituents because these products (well soluble in water) were difficult to isolate. These substituents were successfully synthesized upon changing the process conditions: we employed methyl alcohol as the solvent and conducted the reaction for 1.5 – 3 h at 20 – 60°C in the presence of K2CO3. The proposed structures of the synthesized compounds were confirmed by elemental analyses and by the data of IR, UV, and NMR (H and C) spectroscopy. The IR spectra of all compounds display absorption bands in the region of 1620 – 1720 cm – 1 characteristic of the stretching vibrations CO and =N–C=O of the pyrimidine fragment. The spectra of compounds I and II exhibit the characteristic absorption bands in the regions of 500 – 840 cm – 1 ( CCl) and 1280 – 1290 cm – 1 ( CH Cl 2 ). Absorption bands at 1060 – 1240 cm – 1 are indicative of a tertiary nitrogen atom, and the bands at 3300 – 3500 cm – 1 are due to the stretching vibrations of OH and NH bonds. In the spectra of compounds I, III, V, VII, and IX, the front of the latter band was displaced to 3400 cm – , probably, because the hydroxy group at C participated in a hydrogen bond formation. The C NMR spectra of all compounds exhibited well-known signals due to carbons of the uracil fragment. However, the signals from C in the spectra of compounds I, III, V, VII, and IX were shifted to 102.87 ppm. Apparently, all compounds are featuring a strong hydrogen bond between the hydroxy groups of C and the keto group. This results in a significant difference between C NMR signals from carbons of the substituents at N and N, while the signals from C and C shift toward stronger fields: in the absence of hydrogen bonding, the chemical shift of the signal from C must take a theoretical value of about 125.42 ppm. The H NMR spectra display the signals from protons at C and C of the

Alkylation of Pyrimidine Derivatives with Chloroacetic Acid Esters

Alkylation of 6-methyluracil, 5-hydroxy-6-methyluracil, and 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-ylammonium sulfate with isopropyl and ethyl chloroacetates afforded previously unknown alkyl 2-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetates, alkyl 2-(1-alkoxycarbonylmethyl-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)acetates, 1,3-bis(alkoxycarbonylmethyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-ylammonium sulfates, and alkyl 2-[1,3-bis(alkoxycarbonylmethyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yloxy]acetates.

Synthesis of macrocyclic pyrimidine derivatives

A reaction was studied of previously unknown 1,3-bis(2-hydroxy-3-chloropropyl)uracil, 1,3-bis(2- hydroxy-3-chloropropyl)-6-methyluracil, and 1,3-bis(2-hydroxy-3-chloropropyl)-5-fluorouracil with 1,3-bis[3-(3-methyl-2H-5-pyrazolon-1-yl)-2-hydroxypropyl]-6-methyluracil.

Synthesis of 1,3-Bis[2-hydroxy-3-(3-methyl-5-oxo-2,5-dihydro-1-pyrazolyl)propyl)uracils

A reaction was studied of newly synthesized 1,3-bis(2-hydroxy-3-chloropropyl)uracil and 1,3-bis(2-hydroxy-3-chloropropyl)-6-methyluracil with hydrazine hydrate followed by treating the compounds formed with ethyl acetoacetate. The hydrazones obtained cyclized into pyrazolones in the presence of sodium methylate.

Alkylation of pyrimidine derivatives with ethylene chlorohydrin

Alkylation of 6-methyluracil, 5-fluorouracil, uracil-5-ammonium sulfate, 5-hydroxyuracil, 5-hydroxy-6-methyluracil, 3,6-dimethyl-5-hydroxyuracil, and 1,3,6-trimethyl-5-hydroxyuracil with ethylene chlorohydrin in water-alcohol medium in the presence of KOH was investigated.

Synthesis of 2,4-Dioxo-1,2,3,4-tetrahydropyrimidin-5-yl Methacrylates

Abstract2,4-Dioxo-1,2,3,4-tetrahydropyrimidin-5yl methacrylates were synthesized for the first time by reaction of 5-hydroxyuracil derivatives with methacrylic anhydride. 5-Hydroxyuracil derivatives are involved in this reaction in the dioxo form.

Synthesis of 5-Alkyl-1,3-bis[2-hydroxy-3-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)propyl]-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-diones

Abstract6-Methyluracil sodium salt reacts with 1,3-bis(3-chloro-2-hydroxypropyl)-6-methyluracils in DMF, yielding products of alkylation at the nitrogen atom in position 3 of the uracil ring.

Synthesis of 2-(1,5,9-Triazabicyclo[7.3.1]tridec-10-en-5-yl)-4-methylthiobutanoic Acid Derivatives

Reactions of 1,3-bis(3-chloro-2-hydroxypropyl)uracil, 1,3-bis(3-chloro-2-hydroxypropyl)-6-methyluracil, 1,3-bis(3-chloro-2-hydroxypropyl)-5-hydroxy-6-methyluracil, and 1,3-bis(3-chloro-2-hydroxypropyl)-5-fluorouracil with 2-amino-4-methylthiobutanoic acid (methionine) were studied for the first time.

Synthesis and Pharmacological Characterization of New Acyclonucleoside Derivatives

The target pyrimidine acyclonucleosides III – VI were obtained using interactions of 1,3-bis(2-hydroxy-3-chloropropyl)uracil (I) and 1,3-bis(2-hydroxy-3-chloropropyl)-6methyluracil (II) with levomycetin or piperidine. The proposed structures of the synthesized compounds were confirmed and their purity was checked by elemental analyses and by the data of IR, UV, and NMR (H and C) spectroscopy. The IR spectra of all compounds display absorption bands in the region of 1670 – 1715 cm – 1 characteristic of uracil derivatives. Compounds II and IV exhibit characteristic absorption at 690 cm – 1 ( CCl), while the bands at 1060 – 1270 cm – 1 are indicative of the presence of a tertiary nitrogen atom. The absorption bands at 3300 – 3600 cm – 1 are due to the stretching vibrations of OH bonds; the bands at 840 – 890 cm – 1 belong to the stretching vibrations in 1,4-disubstituted aromatic ring ( para position); and the bands at 1450, 1530, 1570, and 3100 cm – 1 are also characteristic of the aromatic ring.