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New lappaconitine, N-deacetyllappaconitine, and lappaconine derivatives with C-19 C–C-bonded substituents were prepared from lappaconitine–isoxazolidine hybrids by reductive and oxidative opening of isoxazolidine rings annelated to the lappaconitine N(20)–C(19) bond.

Oxidative halogenation of lappaconitine and N-deacetyllappaconitine HBr or HCl in the presence of H2O2 in MeOH was associated upon bromination by N-20-deethylation and produced the 3′,5′-dibromo derivative of N-20-nordeacetyllappaconitine; upon chlorination, a mixture of 5′-mono- and 3′,5′-dichloro derivatives of N-deacetyllappaconitine with the monochloro-derivative dominating.

A series of new lappaconitine structural analogs were prepared via esterification of the lappaconine C-4 hydroxyl by aromatic acids.

Bromination of lappaconitine with a KBr—H2O2 mixture in 20% H2SO4, as well as with molecular Br2 in either Py, CH2Cl2, CH3COOH, or DMSO did not occur, while the initial lappaconitine was isolated from the reaction mixture. Such a bromination with molecular Br2 in solutions of strong acids (concentrated HCl, aqueous 50% H2SO4, and CF3COOH) gives monobromolappaconitine in the yields up to 80%. Bromination of N-desacetyllappaconitine both in organic solvents and in acid solutions leads to mono- and dibrominated derivatives.

1-Carboxymethyl-5-halo-6-hydroxy-5-methyl-5,6-dihydrouracils and 1-carboxymethyl-6-hydroxy-5-methyl-5-mtro-5,6-dihydrouracils were synthesized for the first time by oxidative halogenation and nitration of 1-carboxymethyl-5-methyluracil. Dihydrouracil derivatives bearing a Br atom at position C(5) and a hydroxy group at position C(6) treated with Ac2O undergo deoxyhalogenation.

The compositions of neutral lipids (NL) from fruit of L. barbarum, commercially available (I) and introduced (II), and wild L. ruthenicum (III) were studied. The contents of NL in fruit of I (6.1%), II (3.7%), and III (7.54%) and the fatty acid (FA) compositions were determined. The class composition of NL from I, II, and III was established. The FA compositions of all acyl-containing NL classes were determined. The position-forms (21 forms) and types (4 types) of the triacylglyceride (TAG) compositions of II were established using pancreatic hydrolysis. It was shown that the 2-position in TAG molecules was occupied mainly by unsaturated FA.

The data on antiarrhythmic drugs based on diterpene alkaloid lappaconitine are summarized. N-Deacetyllappaconitine is the main metabolite of allapinin and a potential antiarrhythmics for intravenous use. The basicity of two nitrogen atoms of this compound and the possibility of obtaining mono- and di-salts with the example of hydrochlorides and hydrobromides having good solubility in water have been studied. It was shown using NMR spectroscopy and potentiometric titration that in the methanolic solutions the atom N(20) is protonated at the first step (pKb1 = 6.77, 25 °C) in the pH range of 6—7. The nitrogen of the primary aromatic amino group is protonated in the pH range of 2—3 (pKb2 = 2.18, 25 °C).

New functionalized maleopimarimides were prepared. Their cytotoxicity against tumor cell lines (HeLa, HEp-2) was studied. Diterpenoids 6, 9, and 10 with allene fragments possessed the greatest cytotoxicity and could be considered lead compounds with potential antitumor activity.

A series of new functionalized allenoates has been synthesized, and their cytotoxic effect has been studied against the tumor cell line (HepG2 and Jurkat) and the normal origin cells (HEK293). The highest cytotoxic effect has been shown for diterpene-containing allenic compounds, which can be attributed to promising substances with potential antitumor activity.

1-Carboxymethyl-5-fluoro-5-halogeno-6-hydroxy-5,6-dihydrouracils and 1-carboxymethyl- 5-fluoro-6-hydroxy-5-nitro-5,6-dihydrouracil were synthesized in high yields by oxidative halogenation or nitration of 1-carboxymethyl-5-fluorouracil. Oxidative halogenation or nitration of 5-fluoro-1-(methoxycarbonylmethyl)uracil in acidic media results in the addition of the corresponding groups at the C(5) atom of uracil and simultaneous hydrolysis of the ester group. Bimolecular ions of the obtained compounds were detected in the negative ion mass spectra.

In in vitro experiments on isolated rat hippocampal neurons, we studied the electrophysiological mechanisms of the antiarrhythmic effects of N-deacetyllappaconitine monochlorhydrate (DALCh), active metabolite of lappaconitine hydrobromide (allapinin). Electrical activity of neurons was recorded by the patch-clamp method in the whole cell configuration. It was shown that DALCh increased the duration of both slow and fast depolarization phases and decreased the amplitude of the action potential. DALCh effectively inhibited transmembrane currents of Na

The reaction of [3 + 2] cycloaddition of a lappaconitine-based nitrone with N,N-diethylallylamine is accompanied by the formation of two minor products, unusual for the reaction of this type, containing the pyrrole cycle. The structures of the products have been established from the data of 1H and 13C NMR spectra. The mechanism of their formation is proposed.

Oxidative chlorination of 6-methyluracil-5-carbaldehyde oxime in a two-phase system gave 7V-hydroxy-6-methyluracil-5-carboximidoyl chloride, and its bromination afforded ipso-substitution products, 5-bromo-6-methyluracil and 5,5-dibromo-6-hydroxy-6-methyl-5,6-dihydrouracil. The reaction of the title compound with acetic anhydride led to the formation of 6-methyluracil-5-carbonitrile or O-acetyl derivative, depending on the temperature. 7V-Hydroxy-6-methyluracyl-5-carboximidoyl chloride reacted with acetic acid at 100°C or with potassium iodide in boiling acetone to produce uracil-5-hydroxamic acid which was converted with high yields into the corresponding methyl ester and hydroximic acid amide. Quaternary ammonium salts were obtained by reactions of N-hydroxy-6-methyluracil-5-carboximidoyl chloride with pyridine and 1-methyl-1H-imidazole.

Lipids from seeds of Pulmonaria mollis (Boraginaceae) from two RF climate zones, i.e., Krasnodar Krai (I) and Republic of Bashkortostan (II), were characterized. The neutral lipid (NL) contents of I were greater than those of II (33.8 and 20.5%, respectively). The NL classes were characterized. A larger amount of polyunsaturated fatty acids (PUFAs) concentrated in NL and triacylglycerides (TAGs) from I and II [in NL (%, respectively): 65.6 and 65.0, including α-18:2, 28.8 and 31.9; γ-18:3, 18.5 and 14.5; α-18:3, 12.7 and 14.5; 18:4, 5.7 and 4.1; in TAG (%, respectively): 63.5 and 66.0, including α-18:2, 29.4 and 32.3; γ-18:3, 17.15 and 14.36; α-18:3, 12.5 and 14.6; 18:4, 4.5 and 4.7]. Fractions enriched in PUFAs γ-18:3 (47.1%) and 18:4 (21.2%) were obtained. The ω-6/ω-3 ratios in the lipid PUFAs were 2.7:1-2.2:1.

5-Chloro-5-fluoro-6-alkoxypyrimidines were synthesized via Cl2 chlorination of 5-fluorouracil and 1,3-dimethyl-5-fluorouracil in various alcohols and were screened for antiviral activity. High antiviral activity was found for 5-chloro-5-fluoro-6-hydroxy-5,6-dihydrouracil against RS virus and human flu viruses A/H3N2 and A/H1N1pdm09.

N-Substituted amino acids with a norbornene fragment were synthesized by the direct fusion of amino acids with endic anhydride at 150°C. The synthesized compounds were used for one-pot synthesis of novel stable allenes with an exocyclic cumulene group derived from l-phenyl-3-(triphenylphosphoranylidene)-pyrrolidine-2,5-dione has been carried out.

A betulin derivative with an (imidazolium)butane-1-sulfonate fragment was synthesized and promoted proliferation in vitro of HEK293 and human T-lymphocyte cells, suggesting that this compound had immunostimulant properties.

N-Hydroxy-6-methyluracil-5-carboximidoyl chloride was synthesized for the first time, and its halogenation and reactions with amines (imidazole, aniline) were studied. The reaction of the title compound with sodium azide gave the corresponding N-hydroxycarboximidoyl azide. The Z isomer of the latter was stable, and it did not undergo isomerization to the E isomer, which prevented transformation to 1-hydroxytetrazole. 6-Methyluracil-5-carbaldehyde oxime was readily acylated at the oxime oxygen atom.

Conjugates containing a diterpene moiety and pharmacophoric pyrazole or triazole ring were synthesized regioselectively via 1,3-dipolar cycloaddition of diazomethane or methyl-2-azidoacetate to allenoates.

Amides were prepared from N-deacetyllappaconitine and the amino acids glycine, taurine, and γ-aminobutyric acid.

The compositions of lipids, fatty acids (FAs), and triacylglycerides (TAG) from seeds of Pulmonaria obscura growing in the Republic of Bashkortostan were studied. The contents of neutral (NL) and polar lipids and the composition of FAs of all acyl-containing NL classes were identified and determined. The largest amounts of polyunsaturated FAs were concentrated in total NL (88.9%, including γ-18:3, 24.3; α-18:3, 10.4; and 18:4, 3.5%) and TAG (85.3%, including γ-18:3, 21.4; α-18:3, 10.7; and 18:4, 3.5%). The speciation (39 species > 0.5%) and type (three types) of TAG were established using pancreatic hydrolysis.

New cyclopentene-fused [C60]-fullerene derivatives containing terpene moieties have been synthesized by [3 + 2]-addition to fullerene C60. All obtained products were fully characterized by 1H- and 13C-NMR, IR, and MS. The electrochemical properties have been studied by cyclic voltammograms (CV), combined with absorption spectra, which are consistent with those obtained from density functional theory (DFT) calculations. It was found that all fulleropyrrolidines showed very similar absorption spectra, orbital energies, in which electron densities in both the LUMO and HOMO are mainly located on the fullerene cage, suggesting that C60 act as the acceptor. All the compounds exhibited good thermal stability. All determined characteristics of fullerene conjugates were compared to [6,6]-phenyl-C61-butyric acid methyl ester ([60]PCBM), a popular fullerene-containing compound.

Lipophilic conjugates of fullerene C60 were prepared via Bingel [2+1]-cycloaddition of chloromethylketones based on N-maleopimarimide-substituted amino acids to the fullerene framework.

Isoxazolidine derivatives of lappaconitine and talatisamine were prepared by [3 + 2]-cycloaddition of lappaconitine and talatisamine nitrones to allyl alcohol.

Conjugates with adamantyl substituents were synthesized as potentially biologically active compounds via the reaction of aminoadamantane with the anhydride of methyl maleopimarate (MMP) and with the N-maleopimarimide-substituted acid chlorides of α-alanine, β-alanine, valine, and γ-aminobutyric acid.

Treatment of 5-iodo-1,3,6-trimethyluracil or 5-bromo-1,3,6-trimethyluracil with H2SO4 (5%) in the presence of an excess of KI at 80°C for 5 h produced 1,3,6-trimethyluracil as the only product. Analogous treatment of N-bromo-6-iodomethyluracil gave a mixture with 5-bromo-6-iodomethyluracil as the main constituent. The reaction with an excess of KI in MeOH at 50°C formed 5-bromo-6-hydroxymethyluracil, N(1)-iodo-5-bromo-6-hydroxymethyluracil, N(3)-iodo-5-bromo-6-iodomethyluracil, and 5-bromo-6-iodomethyluracil depending on the reaction time.

Conjugates of betulin and betulinic and betulonic acids with 2-aminoethane- and N-methyl-2-aminoethanesulfonic acids were synthesized for the first time and were interesting as potential biologically active compounds. Experiments in vitro in MDCK cell culture using the MTT assay found that betulin and betulinic-acid derivatives with aminoethanesulfonic acid bound to triterpene C-3 or C-28 through an ester linker were less toxic than the native compounds.

N-1 skatyl derivatives were obtained in moderate yields via the reaction of uracil, 5-fluorouracyl, and cytosine with gramine N-oxide or its methyl iodide. Gramine N-oxide was converted into gramine in good yield upon microwave irradiation in DMF solution. Gramine was also formed in DMF solution in the presence of DBU from gramine methyl iodide although microwave irradiation did not affect the yield of gramine. Gramine did not form from its methyl iodide upon microwave irradiation without DBU.

The compositions of lipids and lipophilic constituents from seeds of Symphytum officinale L. (Boraginaceae Juss., comfrey) were studied. Neutral and polar lipids were identified and quantified. The fatty-acid composition was determined. It was found that the greatest amounts of polyunsaturated fatty acids (PUFA) were concentrated in total NL (57.6%, including 16% γ-linolenic acid) and triacylglycerides (56.5%). A fraction with 99% PUFA, including 72% γ-linolenic acid, was obtained as clathrates with urea. Lipophilic constituents, i.e., sterols, were identified.

The formation of negative ions of some diterpene alkaloid molecules having conjugated πС=С and πС=О bonds in their structure by resonance electron capture has been studied. The mass spectra of these compounds are due to electron capture onto the lowest unoccupied molecular orbital (LUMO), which is π*-С=С or π*-С=О in nature. It has been found that the partial conversion of the test compound molecules into the enol form is possible on transferring into a gas phase; for this purpose, the appearance potentials of the ions (M–H)– and (M–OCH3)– have been compared with the calculated thermodynamic thresholds of their appearance in the keto and enol forms.