Search

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.

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.

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.

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.

A new zwitterionic derivative of the lupan pentacyclic triterpenoid series, viz., the sulfobetaine with a 4-(dimethylammonio)butane-1-sulfonate moiety, was synthesized by quaternization of betulin 28-(2-dimethylaminoacetate) with 1,4-butane sultone. The sulfobetaine was found to possess a dose-dependent proliferative effect toward human embrionic kidney cells HEK293 and human T-lymphocytes. Betulin chosen as a comparison compound demonstrated an effect against cells of both the tumor (HepG2, Jurkat) and the normal origin (human HEK293 and T-lymphocytes) which differ from that of the sulfobetaine, inhibiting their proliferation. The new sulfobetaine can prove to be a promising basis for the development of reparative and immunostimulating agents.

5-Bromo-5-fluoro- and 5-chloro-5-fluoro-6-hydroxy-5,6-dihydrouracils were obtained in high yields by oxidative halogenation of 5-fluorouracil. Nitration of 5-fluorouracil gave 5-fluoro-6-hydroxy-5-nitro-5,6-dihydrouracil. Theoretical calculations in B3LYP/6-311+G(d,p) // B3LYP/6-311G(d,p) + IEFPCM approximation and GIAO simulation of 13C NMR spectra and spin-spin coupling constants agree with the structure of the compounds obtained, which manifest an equatorial orientation of the fluorine atom and an axial orientation of the hydroxy group at position 6 of the dihydrouracil ring. The principal possibility of oxidative iodination of 5-halouracils was studied in B3LYP/CEP-121G approximation. It was found that reversible elimination of iodine by a nucleophilic agent to give the original compounds is the main transformation pathway of the intermediate in this process.

A series of potentially biologically active betulin derivatives containing various C-28 2-uracilacetoxy substituents were synthesized.

12-N-β-Hydroxyethylcytisine derivatives containing Cl, Br, and nitro groups on the 2-pyridone core were synthesized. Their antiarrhythmic activity was studied in vivo.

The Diels–Alder adducts of the quinolizidine alkaloids N-methylcytisine, (−)-leontidine, and (−)-thermopsine with N-phenylmaleimide have been synthesized. The structures and absolute configurations of the new asymmetric centers of the products were determined by NMR spectroscopy experiments, QC-calculations, and X-ray data.

The neuropharmacological activity of two (–)-cytisine derivatives with adamantyl fragments was studied. It was shown that N-1-adamantylcytisine-12-thiocarbamide exhibited in tests in vivo a pronounced mnestic effect, increased the lifespan of laboratory animals under hypoxic conditions, and also enhanced in vitro binding of transcription factors NFAT and NF-κB to the DNA sequences corresponding to them.

The structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate is determined by X-ray crystallography and further used to elucidate the structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate, using the data of homo- and heteronuclear 2D NMR correlation spectroscopy.

The antiviral activity of several amides and thio- and carboxamides of (-)-cytisine in addition to bromination and nitration products of its 2-pyridone core was studied. Compounds with a selectivity index close to 10 were found.

Impurities of free aromatic amino acids (Phe and Tyr) and the elastin protein were found in the heparin commercial drug (Hep) by spectral luminescent and spectrophotometric methods. The fluorescence quenching of the Trp, Tyr, and Phe amino acids by the Hep drug was studied, and the Stern-Folmer constants (K) that reflected stability of the Hep complexes with amino acids were determined. The stability of AA-Hep complexes increased in the following sequence: Trp < Tyr < Phe (K = 19 ± 2 < 39 ± 3 < 710 ± 70 M−1, respectively). These values probably determined the dominant contribution of the phenylalanine impurity in the heparin drug. The contamination of animal elastin whose structure differed from that of the human elastin is thought to be a reason for allergic reactions and even anaphylactic shock during medical treatment with this drug.

Oxidation of betulin by pyridinium dichromate, pyridinium chlorochromate, and K2Cr2O7 -H2SO4 in the presence of tetrabutylammonium bromide was studied. Products of regioselective C-3, C-28-, and exhaustive oxidation, 28-hydroxylup-20(29)-3-one, 3β-hydroxy- and 3-oxolup-20(29)-en-28-al were obtained.

A new alkaloid, anhydrolycaconitine (C36H46N2O9), was isolated from roots ofAconitum septentrionale K. Based on the results of1H and13C NMR and IR spectroscopy and mass spectrometry of the alkaloid and the product of its alkaline hydrolysis and on the data of X-ray diffraction analysis of the hydrolysis product, the structure of 1α, 6β, 14α, 16β-tetramethoxy-7-oxo-18-succinylanthranoyloxy-17-(7→8)abeo-aconane was assigned to anhydrolycaconitine.

A mixture of two new norditerpene alkaloids consisting of two regioisomers was isolated from the total alkaloids of Delphinium cuneatum roots. Their structures were proposed as 16-demethoxydelavaine (2a and b) on the basis of PMR, 13C NMR, IR, and mass spectra.

The known alkaloids deltaline, methyllycaconitine, elasine, and the new norditerpene alkaloid alpinine were isolated from the aerial part of Delphinium alpinum. The structure of the last was proposed as 1α,6β, 16β-trimethoxy-7-hydroxy-8-ethoxy-14α-propionyloxy-4β-(2″-methyl)succinylanthranoyloxymethyl-N-ethylaconitane on the basis of PMR, 13C NMR, IR, and mass spectra.

The structure antiarrhythmic/arrhythmogenic activity relationship of approximately 200 diterpenoid alkaloids and their derivatives is studied.

The Pictet—Spengler condensation of bis-β-phenylethylbenzylamines with a central diphenyl ether group has given a new series of substituted bis-2-benzyltetrahydroisoquinolines the fragmentation of which under electron impact is determined by the properties that are characteristic for the monomeric compounds and is associated with the successive elimination of the two tetrahydroisoquinoline nuclei, the features of which depend on the mutual positions of the substituents in the diphenyl ether part of the molecule.

Fourteen previously undescribed bases of the bis-β-phenylethylbenzylamine series with a central diphenyl ether group differing by the relative positions of the oxygen bridge and the β-phenylethylbenzylamine substituent have been synthesized. The main directions of the fragmentationof these compounds under electron impact are competing single or successive processes of cleavage of the benzyl bonds, accompanied by the structuredependent transfer of hydrogen atoms.

The structure of a new diterpenoid alkaloid acozerine isolated from Aconitum zeravshanicum has been elucidated by mass, NMR and IR spectral data.

The known norditerpenoid alkaloid mesaconitine and a new alkaloid acsonine 1 were isolated from the roots of Aconitum kusnezoffii Reichb. The structure of 1 was established based on spectroscopic data.

Two new alkaloids, Septonine (C35H44N2O9) and Septontrionine (C25H39NO6) were isolated from the roots of Aconitum septentrionale K. According to the 1H and 13C NMR, IR, and mass spectra, Septonin and Septontrionin were assigned the structures of 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-6-oxo-17(7→8)abeoaconitan-4-ylmethyl 2-(2,5-dioxopyrrolidin-l-yl)benzoate and 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-4-methoxymethyl-17(7→8)abeoaconitan-6-one, respectively.

The known alkaloids isolappaconitine (I), 9-deoxylappaconotine (II), lycaconitine (III), puberaconitine (IV), lycoctonine (V), ranaconitine (VI), ajacine (VII), and septentriodine (VII), and an unidentified alkaloid with mp 203–205°C have been isolated from the epigeal part of the Far-Eastern plantAconitum rubricundum.

It has been established by the x-ray structural method that a new alkaloid isolated from the epigeal part ofAconitum coreanum has the structure of 13-acetyl-14-hydroxy-2-isobutyrylhetisine N-oxide. This is the first time that a N-oxide has been isolated among the hetisine alkaloids.

Exo-2-amino-exo-3-aminomethylbicyclo[2.2.1]heptane (I) and 5-amino-exo-3-azatricyclo[5.2.1.02,6]decan-4-one (II) were synthesized and characterized with respect to antiarrhythmic activity. Compound II exhibited antiarrhythmic activity with ED50 = 0.28 and 0.33 mg/kg on the aconitine and calcium chloride models of arrhythmia, respectively. Compound I did not show antiarrhythmic activity and exhibited acute toxicity corresponding to LD50 = 450 mg/kg.

A new norditerpenoid alkaloid has been isolated from the roots of Delphinium cuneatum. On the basis of 1H, 13C NMR, IR, and mass spectra, the structure of the alkaloid was established as 1α,6β,14α-trimethoxy-7,8-dihydroxy-18-(2″-methyl)succinylanthranoyloxyaconane (16-demethoxymethyllycaconitine). The roots of Delphinium cuneatum also contain the known alkaloid methyllycaconitine and N,N"-di(methoxycarbonyl)-3,4-diaminotoluene.

Michael reactions of methyl (ethyl) 1-benzyl-4-oxopiperidine-3-carboxylates with a number of α,β-unsaturated carbonyl compounds result in formation of 6- and 6,8-substituted methyl (ethyl) 3-benzyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylates. Stereochemical aspects of these reactions were studied, and some further transformations of the products were performed.

From the epigeal part of the previously unstudied plantAconitum sajanense we have isolated the new alkaloid acosanine, the structure of which has been established on the basis of spectral characteristics and has been confirmed by a direct comparison with a sample of demethyldelcorine.

A new alkaloid has been isolated from the epigeal part ofAconitum coreanum (Levl.) Rapaics, for which the structure of 14-hydroxy-2-isobutyrylhetisine N-oxide has been established on the basis of spectral characteristics and a chemical transformation.

A new alkaloid, ternatine (C24H33NO5), was isolated from aerial parts of theDelphinium ternatum plant. According to the1H,13C NMR, IR, and mass spectra of the base and its triacetate, ternative was assumed to have the structure of 4β-methyl-7α-isobutyryloxy-11α,15β,19β-trihydroxyhetisane.

The structure of a new diterpenoid alkaloid acozerine isolated from Aconitum zeravshanicum has been elucidated by mass, NMR and IR spectral data.

The mass spectra of 53 alkaloids and their derivatives are considered. It is known that the presence of a C6(OCH3)-C7(OH)-C8 (OH) grouping in C19-diterpene alkaloids leads to a high intensity of the (M - 15)+ ions at the expense of the C6(OCH3) group and considerably suppresses the competing processes of forming the [M - OH (OCH3)]+ ions in the alkaloids and the (M - 56)+ ions in the anhydroxy bases. When the above-mentioned grouping is absent, the (M - 15)+ ions are formed mainly by the splitting out of a ĊH3 from a N-ethyl group.

The structure of the new alkaloid aconifine, which has been isolated from the tubers and epigeal part ofAconitum karakolicum Rapcs. has been established on the basis of the results of chemical transformations and spectral characteristics. Some features of the selective acetylation of aconitine and aconine have been elucidated.

From the results of an x-ray structural analysis of free dictysine it has been established that dictysine is an alkaloid of the denudatine type with anα, β, γ-triol system at C15, C16, and C20. The structures of the acetonides of dictysine and dehydrodictysine formed from dictysine and dehydrodictysine, respectively, in the process of separating the combined alkaloids, have been shown.

The results are given of an investigation of the structure of the new diterpene alkaloid dictysine C21H33NO3 isolated from the epigeal part ofDelphinium dictyocarpum DC. On the basis of the results of a study of chemical and spectral characteristics, dictysine has been shown to have the sengorine skeleton, with hydroxy groups at C15, C16, and C20.

As the result of a study of chemical transformations and spectral characteristics, for the new alkaloid karakolidine a lycoctonine skeleton with N-ethyl and C4-methyl groups, hydroxy groups at C1 (α), C8, C10 (α), and C13, and a methoxy group at C15 (β) has been established.

The known alkaloids phenyl-β-naphthylamine, karakoline, neoline, delsosine, monticamine, songorine, napelline acetylnapelline, napelline-n-oxide, and isoboldine and two new alkaloids, which have been called karasamine (I) and 1-benzoylkarasamine (II), have been isolated from the epigeal part ofAconitum karakolicum Rapaics. The structure of the new alkaloids have been shown by the preparation of the mono- and triacetates (IV) and (VI) of karasamine and its carbinolamine derivative (V), and also by the direct passage from karakoline (III) to karasamine (I) and 1-bezoylkarasamine (II) and by a study of their spectral characteristics.

The structure of the new alkaloid N-acetylsepaconitine, and also of a base (IV) formed from lycaconitine in the process of ethanolic extraction in an alkaline medium have been determined on the basis of spectral characteristics. Both bases were isolated from the epigeal part ofAconitum leucostomum.

The mass-spectral properties of 21 lycoctonine bases with 1-methyoxy-7,8-methyl-enedioxy groups have been studied and generalized. An influence of a methyl-enedioxy group of the nature of the substituents at C-6 and C-10, and of a Δ10(12) bond on the fragmentation of the alkaloids and their derivatives has been found.

The roots ofAconitum monticola have yielded songorine, songaramine, norsongorine, an amorphous base with the composition C22H35NO6, a base C22H33NO6 with mp 166–167°C, a base C22H33NO5 with mp 161–164°C, and the new alkaloid acomonine. The structure of acomonine has been established on the basis of chemical transformations and spectral properties: It consists of a lycoctonine nucleus with an α-hydroxy group at C3, an α-methoxy group at C10,β-methoxy groups at C6 and C15, an α-glycol system at C7 and C8, and a methoxy group at C19.

The epigeal part ofAconitum talassicum M. Pop. has yielded, in addition to five alkaloids known previously, kobusine, pseudokobusine, and the new alkaloid actaline. The structure of the latter has been established on the basis of an x-ray structural analysis. Actaline is the first C20 diterpene alkaloid with a lycoctonine skeleton.

An analysis of literature material has shown that the stability of the M+ ions of bases with the hetisine skeleton decreases considerably when an OR group is present at C-1, C-6, or C-9. The directions of fragmentation are not monotypical and depend greatly on the positions of the oxygen substituents. A similar conclusion can be made from a study of the group and individual features of the breakdown of hetisine, nominine, talatisine, and their derivatives revealed with the aid of high-resolution mass spectrometry and MD spectra. An unusual property of these spectra is the formation of nitrogen-free fragments. The mass spectra of hetisine alkaloids of a new type — zeraconine and its N-oxide — have been characterized.

As the result of a study of the influence of solvents on the parameters of the NMR spectra of a number of phthalide-isoquinoline alkaloids it has been established that benzene causes changes of different magnitudes in the CSs of the 4′-OCH3, 5′-OCH3, and N-CH3 protons in the erythro and threo series. Furthermore, it has been found that TFA causes specific changes in the CSs and SSCCs of the H1 and H9 protons in the bases of these series. The possibility has been shown of using the results of the influence of different solvents to solve structural and stereochemical problems in the study of the alkaloids phthalide-isoquinoline series.