This article presents results of histochemical analysis of aerial and underground organs of Anabasis salsa (C. A. Mey.) Benth. ex Volkens growing in the Central Kazakhstan. The localization of active substances in medicinal raw materials was determined using histochemical reactions.Presence of essential oil, alkaloids, sesquiterpene lactones, flavonoids, phenolic compounds, polysaccharides in plant organs (shoots, inflorescences and roots) was established. This species is used in traditional medicine as a diuretic, antispasmodic, analgesic, and is also used to treat skin diseases. Purpose of the study: carrying out a histochemical analysis of Anabasis salsa growing in the Central Kazakhstan. Materials and methods: The object of the study is cross sections of shoots and root and surface preparation of Anabasis salsa fruits. Samples of raw materials were fixed in Strauss-Fleming solution, cross sections and surface preparation were prepared manually, after which histochemical reactions were carried out to identify the following biologically active substances: essential oil, flavonoids, alkaloids, polysaccharides and sesquiterpene lactones. Identification of qualitative coloring was carried out by optical microscopy using histochemical tests according to the methods of the State Pharmacopoeia of the Republic of Kazakhstan. Results: The localization of biologically active substances in the studied type of raw material was determined using histochemical methods with light microscopy. The presence of pharmacologically active classes of compounds has been established. Conclusion: For the first time, the localization of secondary metabolites in the plant raw material of Anabasis salsa was studied using histochemical tests. The results of experimental studies can be used to confirm the authenticity, identification and standardization of the aboveground and underground parts of this species.

Производные никотиновой кислоты обладают широким спектром биологической активности и находят различное применение в медицинской практике в качестве препаратов первой линий для лечения туберкулеза [1], легочной артериальной гипертензии [2], эпилепсии, зависящей от витамина B6 [3], ингибиторов фактора свертывания крови IXa [4,5], ингибиторов вируса иммунодефицита человека [6,7] и др. Следует отметить, что пиридиновый цикл входит в состав многих жизненно важных органических соединений, что определяет одну из его доминирующих ролей среди гетероциклов. Поэтому разработка удобных методов синтеза новых производных никотиновой кислоты является актуальной проблемой, поскольку эти соединения представляют интерес как в практическом, так и в теоретическом плане. Целью данной работы является целенаправленный синтез азида никотиновой кислоты и осуществление его дальнейшей модификации с целью получения новых фармакологически активных соединений. В настоящей работе осуществлен синтез азида никотиновой кислоты взаимодействием нитрита натрия с гидразидом никотиновой кислоты с выходом 99%. Изучено взаимодействие азида никотиновой кислоты со спиртами (изопропиловый и бутиловый спирты) и вторичным амином (алкалоидом цитизином). Показано, что при нагревании в среде сухого бензола азид никотиновой кислоты претерпевает перегруппировку Курциуса, с образованием изоцианата, который далее реагирует in situ со спиртами и амином (алкалоидом цитизином) с образованием соответствующих уретанов и мочевины. С целью синтеза производных 1,2,3-триазола осуществлено взаимодействие азида никотиновой кислоты с терминальным ацетиленом - проп-2-иниловым эфиром 3-трет-бутил-5-этил-2-гидроксибензойной кислоты в среде ДМФА и нагревании (70-80оС) в присутствии медного купороса СuSO4×5H2O и аскорбата натрия (NaAsc). Установлено, что в результате реакции образуется не ожидаемое 1,2,3-триазольное соединение, а 3-аминопиридин и исходное ацетиленовое соединение. Показано, что при нагревании получаемый азид разлагается с образованием промежуточной частицы - нитрена, и последующая миграция пиридильного радикала к атому азота (перегруппировка Курциуса) приводит к изоцианату. В результате гидратации изоцианата и последующего декарбоксилирования из образовавшейся карбаминовой кислоты получается 3-аминопиридин. Строение синтезированных соединений подтверждено на основании анализа данных ЯМР 1Н- и 13С-спектроскопии, а также двумерных спектров COSY (1H-1H) и HMQC (1H-13C).

The article presents the results of a study of the amination reaction of nicotinic acid chlorohydride with amines morpholine, cytisine, and 1-aminoadamantane, which are often used in the search and creation of drugs for respiratory and circulatory stimulants. The study was conducted to search for new biologically active compounds with anti-inflammatory activity. The synthesis of new aminoamides was carried out by the interaction of nicotinic acid with molecules of morpholine, cytisine, and adamantane in anhydrous ethanol. As a result of the conducted studies, new amides of nicotinic acid with high yields (90.7–93.1%) were obtained. The structures of the new compounds were determined using NMR 1H and 13C spectroscopy methods, as well as data from two-dimensional spectra of COSY (1H-1H), HMQC (1H-13C), HMBC (1H-13C) and mass spectrometry. The results of an experimental study of the anti-inflammatory activity of synthesized new amides are presented. The anti-inflammatory effect of nicotinic acid N-adamantylamide was established, other new amides were ineffective compared with ibuprofen (p2 < 0.05).

The reactions of lupinine alkaloid and its chlorine derivative with cinnamoyl chloride and 2-K-isoindole-1,3-dione were investigated to obtain 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester and 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione, respectively. The optimal conditions for carrying out the aforementioned reactions were determined, taking into account the nature of the solvent and medium. It was established that acylation of the molecule in a benzene medium, in the presence of trimethylamine, resulted in the formation of 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester, with an 82% yield. It was demonstrated that the interaction of chlorolupinine with 2-K-isoindole-1,3-dione under Gabriel reaction conditions resulted in the formation of 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione. The conformer with an axial orientation of the isoindole-1,3-dione substituent was observed to exhibit greater stability than the conformer with an equatorial orientation. The structure of the synthesized compounds was investigated by IR, 1H, and 13C NMR spectroscopy. The use of two-dimensional spectra in COSY (1H-1H) and HMQC (1H-13C) formats enabled the establishment of homo- and heteronuclear interactions, thereby confirming the structure of the compounds under investigation. The values of chemical shifts, multiplet and integrated intensity of 1H and 13C signals in one-dimensional NMR spectra of the novel compounds were determined. The crystal structures of 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester and 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione were elucidated through X-ray analysis.

Развитие собственной фармацевтической, медицинской и пищевой промышленности в Казахстане должно базироваться на устойчивой сырьевой базе. В этой связи, изучение ресурсов лекарственных растений имеет важную задачу для полной оценки потенциала практического использования сырья при производстве фитопрепаратов. Особый интерес в этом плане представляют хинолизидиновые алкалоиды анабазин и лупинин, которыми богаты дикорастущие виды растений Республики Казахстан, к ним относится ежовник (Anabasis L. сем. Chenopodiaceae Vent.). В статье приводится обзор литературы лекарственного растения рода Anabasis L. Из анализа литературных данных следует, что в арсенале лекарственных средств доминирующее положение занимают индивидуальные фитохимические препараты, среди которых около 30% являются алкалоид-содержащие соединения, их функциональные или другие азотсодержащие производные. Проблемы выделения новых соединений алкалоидов, установления их строения, изучение их биологической активности, взаимосвязей структуры — активности и разработка лекарственных препаратов на их основе — основные направления работы сотрудников ИОСУ данной тематике. Полученные данные послужат основой для научных исследований данного растения, выделению алкалоида лупинина высокой чистоты для создания нового лекарственного вещества.

Aminophthalide derivatives of cytisine, anabasine, and salsoline were obtained in high yields via condensation of the alkaloids with o-formylbenzoic acid. Their structures were proven using 1H and 13C NMR spectroscopy and data from 2D COSY 1H–1H and HMQC 1H–13C spectra. Studies of their antimicrobial activity showed moderate antimicrobial activity of 3-(N-cytisin-1-yl)isobenzofuran-1(3H)-one and 3-(N-salsolin-1-yl)isobenzofuran-1(3H)-one against Gram-positive test strain Staphylococcus aureus ATCC 6538 and Gram-negative test strain Escherichia coli ATCC 25922.

The article describes the results of studies on the synthesis and structural features of 4-lupinylbenzaldehydes and azomethine derivatives of the lupinine alkaloid. Chemical modification of the lupinine alkaloid was carried out by the halomethylene group in the C-1 position of the quinolysin backbone. The reactions were carried out in several stages. The results of the synthesis of 4-lupinylbenzaldehydes (4-hydroxybenzaldehyde and 4-hydroxy-3-ethoxy-benzaldehyde) synthons in the synthesis of biologically active substances with yields of 67.3% and 74.0%, respectively, are presented. The interaction of 4-lupinylbenzaldehyde with 4-chlorobenzylamine and vinyl ester of monoethanolamine synthesized lupinyl-containing azomethines with yields of 78.4% and 77.4%, respectively. The structure of the obtained compounds was established based on the analysis of the ¹H and 13C NMR spectra, the multiplicity of signals in the 13C NMR spectra was determined from the spectra recorded in the J-modulation mode. The assignment of signals in the spectra was carried out using various modern methods of correlation spectroscopy 1H-1H (COZY), and 1H-13C (HMBC, HSQC). The values of chemical shifts, multiplicity and integral intensity of 1H and 13C signals in one-dimensional NMR spectra are determined. Bioscreening of new 4-lupinylbenzaldehydes and azomethines was carried out, among which substances with high antimicrobial activity were identified. The antimicrobial activity of all the presented samples was studied on reference test microorganisms: facultative anaerobic gram-positive cocci of Staphylococcus aureus ATCC 6538, aerobic gram-positive spore-forming Bacillus subtilis ATCC 6633, gram-negative rods facultative anaerobes of Escherichia coli ATCC 25922 aerobic Pseudomonas aeruginosa ATCC 27853 and yeast fungus Candida albicans ATCC 10231 by diffusion into agar (wells).

The article presents results on the synthesis and investigation of the structural features of a number of 1,4-disubstituted 1H-1,2,3-triazole derivatives of the alkaloid lupinine. Lupinine modification reactions have been carried out at the hydroxymethylene group in the C-1 position of the quinolysine backbone. It has been shown that (octahydro-2H-quinolysine-1-ylmethyl)methanesulfonate in high yield (93%) is formed by the in-teraction of lupinine with methanesulfonyl chloride in methylene chloride. Subsequent treatment of this com-pound with sodium azide in dimethylformamide on heating leads to the formation of 1-(azidomethyl)octahydro-2H-quinolysine in 61% yield. It has been found that the reaction of a new azide with terminal alkynes of various nature in the presence of aqueous СuSO4 and sodium ascorbate in dimethylfor-mamide can form the corresponding 4-substituted (1S,9aR)-1-[(1,2,3-triazol-1-yl)methyl]octahydro-1H-quinolysines. New 1,2,3-triazole derivatives of lupinine containing various aryl substituents at the C-4 posi-tion of the triazole ring have been obtained. The high selectivity of the reaction is explained by the action mechanism of the Sharpless catalyst. The spatial structure of the molecules of lupinine methanesulfonate, 4-aryltriazolylmethyl-octahydroquinolysines has been established by X-ray diffraction analysis. X-ray structur-al analysis data of new compounds have been deposited in the form of CIF files at the Cambridge Crystallo-graphic Data Center

Lupinine is an elementary representative of a large quinolizidine alkaloid group. Referring to a pharmacological action, lupinin has the bactericidal and low sedative effects. It also possesses the short-term anthelmintic and hypotensive properties. The curent research aimed to investigate synthesis methods and study of the hemorological, antimicrobial and cytotoxic activities of lupinine quinolizine alkaloid. The chemical modifications of lupinine molecules were performed with introduction of 1,2,3-triazole substituents for the hydroxymethylene group at C-1 position of quinolizine skeleton. Structure of the obtained compounds was determined by 1Н and 13С NMR spectroscopy. The various correlation approaches of 1H-1H (COSY) and 1H-13C (HMBC and HSQC) spectroscopy were used for it. The evaluation results of the hemorheological, antimicrobial and cytotoxic activities of the obtained (1S,9aR)-1Н-1,2,3-triazol-1-yl)methyl)octahydro-1H-quinolizine derivatives were demonstrated. Some compounds were identified and they are able to affect deformability of red blood cells and aggregation properties of blood. Patterns of the antimicrobial and cytotoxic activities depending on the structural features of the synthesized compounds were determined.

The synthesis of some cytisine derivatives was carried out in the work. The article provides the data of quantum-chemical calculation and virtual screening of the alkaloid cytisine derivatives synthesized. At the same time, the reaction centers of the cytisine derivatives molecules were determined. In order to study the reactivity of the derivatives obtained (namely cinnamoylcytisine, lipoylcytisine, and cytisinylisoalantholactone) the quantum-chemical calculations were conducted to determine the energy and charge characteristics of the molecules. The results indicate a sufficient thermodynamic stability of the cinnamoylcytisine and lipoylcytisine molecules. The cytisinylisoalantholactone molecule is not stable according to the results of quantum chemical calculations. The data on the energy values of the frontier molecular orbitals show that, in general, all molecules exhibit electrophilic properties. A bioprediction was implemented using PASS (Prediction of Activity Spectra for Substances) as one of the most efficient and well-known computer program with the aim of detailed study and the probable establishment of the biological activity of the synthesized cytisine derivatives. Based on the results of virtual screening, promising types of alkaloid cytisine derivatives were identified, which are potential sources of original drugs.

The article presents data on the synthesis and study of the structure of thiourea derivatives of functionally substituted pyridines. New thiourea derivatives containing a pharmacologically active pyridine moiety in their structure were obtained. As the starting synton, 2-amino-5-bromopyridine, 2-amino-3-hydroxypyridine and 2-aminomethylpyridine were selected. It was shown that the interaction of 2-amino-5-bromopyridine, 2-amino-3-hydroxypyridine and 2-aminomethylpyridine with ethyl and phenylisothiocyanates in ethanol leads to the formation of the corresponding pyridine-containing thioureas. The synthesis of the initial isothiocyanates was carriedout in situ from the corresponding acidic chlorides (benzoyl chloride and p-brombenzoyl chloride) by heating them with potassium thiocyanate in acetone. The structure of the synthe-sized compounds was studied by 1H and 13C NMR spectroscopy, as well as by the data of two-dimensional spectra of COSY (1H-1H) and HMQC (1H-13C). The values of chemical shifts, multiplicity, and integrated in-tensity of 1H and 13C signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (1Н-1Н) and HMQC (1Н-13С), homo-and heteronuclear interactions were established, confirming the structure of the studied compounds.

This review has been summarized the data on the synthesis of new hybrid derivatives based on alkaloid molecules. At the same time, there have been analyzed methods for obtaining hybrid structures containing fragments of natural compounds molecules in combination with other biologically active plant metabolites, as leading compounds for the development of new pharmacologically valuable agents, with the aim of creating new original drugs. The combination of pharmacophoric residues in one molecule, namely various aromatic and heterocyclic substituents in the nucleoside position of natural alkaloids, opens up new possibilities for both the subsequent chemical modification of the polyfunctional derivatives obtained and their new diverse biological activity. Effective methods of synthesis have been developed on the basis of directed transformations of these compounds (or their precursors). A wide range of pharmaco-logical properties of combined compounds of these series with a combination of low toxicity is promising. Considering that the preparation of combined derivatives based on alkaloid molecules has been insufficiently studied, the targeted synthesis of new com-pounds is of interest both in terms of new medicinespreparation and the development of new methods of organic synthesis, as well as the molecules stereochemistry determination of a new series of compounds.

The modification of the quinolysin alkaloid lupinine was carried out with the intro-duction of 1,2,3-triazolyl substituents for the hydroxymethylene group in the C-1 position of the quinolysin backbone. The reaction of lupinine with methanesulfochloride in the presence of triethylamine smoothly led to lupinine methanesulfonate, whose further reaction with sodium azide in DMFA led to lupinilazide. 1,3-Dipolar [4+2]-cycloaddition of the resulting azide to alkynes produced more stable 1,2,3-triazole compounds. The interaction of lupinilazide with 2-ethinylpyridine and with alcohols containing a terminal acetylene group (propargyl alcohol, 2-methylbut-3-in -2-ol or hex-5-in -1-ol) proceeded smoothly in the DMFA medium. The reactions were carried out in the presence of an aqueous solution of CuSO4 and sodium ascorbate in DMFA and allowed the corresponding 4-substituted (1S,9aR)-1H-1,2,3-triazol-1-yl to be synthesized with good yields)methyl)octahydro-1H-quinolysins. The results of studying the structural features of synthesized compounds by 1H - and 13C - NMR spectroscopy, as well as data from the two-dimensional COSY (1H-1H) and HMQC (1H-13C) spectra are presented. The values of chemical shifts, multiplicity and integral intensity of 1H and 13C signals in one-dimensional NMR spectra are determined. In the spectra of all synthesized new quinolizi-dinotriazoles, there is a peak of the fragmentary C10H17N ion (150-151 cu), corresponding to the cleavage of the molecule by the C-10 atom of the quinolizidine backbone.

This work presents the results of studies on the chemical transformation of the alkaloids molecules cytisine and anabazine to obtain their N-cinnamoyl derivatives, as well as possible ways for their further modification. The optimal conditions for the preparation of N-cinnamoylcytisine and N-cinnamoylanabazine in the acylation reactions of alkaloids with cinnamoyl chloride are considered. Hydrazinolysis of the resulting N-cinnamoylcytisine and N-cinnamoylanabazine was carried out. It was shown that the interaction of acrylamide derivatives of alkaloids with hydrazine hydrate in ethanol leads to the formation of the corresponding pyrazole derivatives resulting from the intramolecular cyclocondensation of hydrazones of N-cinnamoyl derivatives. By the interaction of cinnamoylisothiocyanate with the above alkaloids, new thiourea derivatives are synthesized. The structures of the synthesized compounds were studied by( 1)H and C-13 NMR spectroscopy, as well as by the data of two-dimensional spectra of COSY (H-1-H-1) and HMQC (H-1-C-13). The values of chemical shifts, multiplicity, and integrated intensity of H-1 and C-13 signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (H-1-H-1) and HMQC (H-1-C-13), homo- and heteronuclear interactions were established, confirming the structure of the studied compounds.

В результате изучения взаимодействия хлорлупинина с фталимидом калия найдены оптимальные условия синтеза N-лупинилфталимида в рамках метода Габриэля. Для N-лупинилфталимида методом РСА впервые определена кристаллическая структура. Методом квантовой химии рассчитаны энергетические характеристики. Установлено, что конформер с конформациями кресло циклов с аксиальной ориентацией фталимидного заместителя более устойчив, чем с экваториальной.

For the first time, synthesis of 8-formylharmine by the Vilsmeier reaction was carried out. 8-Formylharmine was obtained by treating alkaloid harmine with dichloromethoxymethane in the presence of SnCl4.The yield of the target product was 64 %. The structure of the obtained compound was established on the basis of 1H and 13C NMR spectroscopy as well as mass-spectrometry data. The crystalline structure of 8-formylharmine was determined by X-ray diffraction. It has been shown that the replacement of the hydrogen atom in the harmine molecule with a formyl group occurs at the C8 atom. It was revealed that the methoxy group at the C7 atom changes its orientation to the opposite one as compared to the orientation in the harmine molecule and its salts due to the mutual Van der Waals repulsion of the methoxy and formyl groups. A weak intramolecular hydrogen bond was found in the crystal between the O2 atom of the formyl group and the hydrogen atom of the secondary amino group. It was shown that molecules in the crystal form an intermolecular hydrogen bond between the same atoms (О2 and НN9A), as a result of which dimers are formed.

Acylation of the alkaloid lupinine produced O-cinnamoyllupinine and O-lipoyllupinine. The structure of O-cinnamoyllupinine was established by an X-ray crystal structure analysis.

The reactions of the cytisine and anabasine alkaloids with cinnamic acid chloride have been studied, and hydrazinolysis of the resulting N-cinnamoylcytisine and N-cinnamoylanabazine has been carried out. The reaction of cinnamoyl isothiocyanate with alkaloids has afforded the corresponding thiourea derivatives. Antimicrobial and cytotoxic activity of cinnamoyl-containing derivatives of these alkaloids has been evaluated.