Journal of Organic and Pharmaceutical Chemistry最新文献

{"title":"The Selection of “Green” Conditions for Components Identification in a Combined Medicine by TLC/HPTLC Methods","authors":"O. V. Rudakova, S. Gubar, N. Smielova, A. Kriukova, N. Bevz, V. Georgiyants","doi":"10.24959/ophcj.22.259691","DOIUrl":"https://doi.org/10.24959/ophcj.22.259691","url":null,"abstract":"Aim. To select “green conditions” for identifying components in a combined medicine for the treatment of alcohol intoxication.Materials and methods. Thin-layer chromatography and high performance thin-layer chromatography methods were used. An analytical GREEnness calculator was applied to assess the environmental friendliness of the analytical procedure.Results and discussion. The choice of mobile and stationary phases that comply with the principles of “green chemistry” and can be used to detect glutamic acid and glycine in the composition of a combined medicine has been substantiated. It has been determined that by the indicators Rf, Rs, ΔRf, α, N, H the most effective for the division is the ethanol (96 per cent) – water (70:30) mobile phase (the length of the solvent front is 10 cm, the application volume is 5 μL), which allows, in addition to amino acids, to determine another prescription component – ascorbic acid. The conditions for identification of substances by the high-performance thin-layer chromatography method (the length of the solvent front is 7 cm, the application volume is 2 μL) have been selected. It has been found that to detect chromatographic zones, it is optimal to use ninhydrin solution R1 with further heating of the plate at a temperature of 100-105°С for 5 min. The specificity of determination of glutamic acid, glycine and ascorbic acid in comparison with solutions of standard substances has been proven. While studying the robustness of the method the influence of chromatographic conditions on the final result (the impact of the stationary phase type, chamber saturation, application volume, distance from the “start line” to the “finish line”, the effect of the detection solution, stability of solutions for application) has been researched. The precision of the method on one and three plates of the same type has been studied; the intermediate precision has been researched. The calculated assessment of greenness of the analytical procedure is 0.66.Conclusions. As a result of the studies conducted, “green conditions” for identifying amino acids (glutamic acid, glycine), as well as ascorbic acid in a combined medicine by thin-layer chromatography and high-performance thin-layer chromatography methods have been selected. The validation characteristics of the method (specificity, robustness and precision) have been studied.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75091734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bianka Tchoubar: A Revolutionary in French Organic Chemistry","authors":"R.-I. Martyniak","doi":"10.24959/ophcj.22.255945","DOIUrl":"https://doi.org/10.24959/ophcj.22.255945","url":null,"abstract":"Virtually unknown in her homeland, Bianka Tchoubar, born in 1910 in Kharkiv, brought about a true paradigm shift in French organic chemistry of the 20th century. Originality of research ideas, scientific rigor and legendary perseverance earned her respect and recognition in the world scientific community. This eccentric Parisian of Ukrainian origin became the first woman to enter the French National Center for Scientific Research (Centre National de la Recherche Scientifique, CNRS) upon its creation in 1939. Bianka Tchoubar’s contribution to the study of reaction mechanisms and salt effects in organic chemistry were of paramount importance, and so were her efforts to present these novel scientific concepts to the audience of French organic chemists through the clear and concise expression of her books. The name of this great Ukrainian researcher may be found in the pages of French organic chemistry textbooks, where the Demjanov ring expansion reaction is called the Demjanov–Tiffeneau–Tchoubar rearrangement. This article aims at presenting the outstanding scientific legacy and turbulent life path of this researcher to the world scientific community.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91208739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and the Antimicrobial Activity of Salt Carbenoid Compounds","authors":"G. Rayenko, Olexandr S. Avksentiev, V. Saberov, A. Ryabitsky, Vasil I. Yenya, O. Komarovska-Porokhnyavets, V. Lubenets, N. Korotkikh","doi":"10.24959/ophcj.22.258880","DOIUrl":"https://doi.org/10.24959/ophcj.22.258880","url":null,"abstract":"Aim. To synthesize aliphatic and aromatic derivatives of salt carbenoid compounds of the series of imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole containing fluorophenyl, cetyl or adamantyl substituents, and study their antimicrobial (antibacterial and antifungal) activities.Results and discussion. New derivatives of heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents were synthesized. For this purpose, reactions of cyclization of the corresponding diimines with ethoxymethyl chloride (imidazolium salts), quaternization of the corresponding azoles with cetyl bromide or 1-adamantyl bromide in organic solvents (benzimidazolium, pyridinium and 1,3,4-oxadiazolium salts), cyclization of di(1-adamantylamino)alkanes hydrobromides with the orthoformic ester (4,5-dihydroimidazolium and tetrahydropyridinium salts) were used. Zwitterionic compounds were obtained by the reaction of the corresponding azolium salts with phenyl isothiocyanate in the presence of potassium carbonate. Some macrocyclic and adamantyl substituted heterocyclic compounds showed antifungal and antibacterial activities.Experimental part. The structure of the compounds synthesized was proven by 1H and 13C NMR spectroscopy methods. The antimicrobial activity was studied out by the agar diffusion method to determine diameters of the growth inhibition zones of microorganisms (bacteria and fungi) and by the method of serial dilutions to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentrations.Conclusions. The synthesis of new heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents has been performed. Compounds of macrocyclic and adamantyl heterocyclic series with antifungal and antibacterial activities have been found. 1,3-Dicetylimidazolium bromide, macrocyclic bis(decylenebenzimidazolium) bromides, azolium-N-phenylthiocarboximides have been proven to be the most active.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76018909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of the extraction frequency of green tea leaves by the antioxidant method","authors":"O. Maslov, M. Komisarenko, S. Kolisnyk, M. Golik, Yevhen O. Tsapko, E. Akhmedov","doi":"10.24959/ophcj.22.252320","DOIUrl":"https://doi.org/10.24959/ophcj.22.252320","url":null,"abstract":"Aim. To determine the optimal extraction frequency of green tea leaves with 60 % ethanol by the antioxidant method.Materials and methods. Chun Myn green tea leaves were the object of the study, the raw material was collected in Anhui province (China) from March to April. Dry green tea leaves were standardized according to the European Pharmacopeia 9.0. Spectrophotometry was used to quantify biologically active substances. The antioxidant activity was determined by the potentiometric method. Potentiometric measurements were performed on a HANNA 2550 pH meter (Germany) with a combined platinum EZDO 50 PO electrode (Taiwan). A UV-1000 spectrophotometer (China) was used to measure the optical density.Results and discussion. The total content of phenolic compounds was 9.60 ± 0.17, 1.30 ± 0.03 and 0.12 ± 0.002 %, catechins – 9.20 ± 0.18, 1.20 ± 0.02 and 0.07 ± 0.002 %, flavonoids – 0.27 ± 0.005, 0.04 ± 0.001, 0.005 ± 0.001, hydroxycinnamic acids – 0.49 ± 0.01, 0.07 ± 0.002 and 0.007 ± 0.001 %, dry residue – 10.75 ± 0.11, 1.59 ± 0.02 and 0.15 ± 0.002 %, the antioxidant activity was 474.08 ± 9.48, 67.70 ± 1.35 and 7.01 ± 0.14 mmol-equiv mdry res-1 for the first, second and third extraction, respectively. According to the results obtained, the optimal number of extractions of the raw material with 60 % ethanol was found to be two.Conclusions. The dynamic of extractions of biologically active substances of green tea leaves has been studied by triple extraction of the raw material to find the optimal extraction frequency; for the first time, a method for determining the extraction frequency based on the antioxidant activity of the extracts has been developed and proposed. It has been found that the optimal extraction rate is 2 times. The results obtained will be used in the further production of herbal medicines, dietary supplements, and cosmetic products with a green tea extract.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81501485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The quantitative content determination of main groups of biologically active substances in batches of Viburnum opulus fruits","authors":"O. Khvorost, B. Leontiiev, Yu. A. Fedchenkova, K. Skrebtsova","doi":"10.24959/ophcj.22.255893","DOIUrl":"https://doi.org/10.24959/ophcj.22.255893","url":null,"abstract":"Aim. To determine the quantitative content of the main groups of biologically active substances (BAS) in batches of Viburnum opulus fruits using pharmacopeial methods for their subsequent use in the standardization of the plant raw material.Materials and methods. For the study, 6 batches of air-dried Viburnum opulus fruits crushed to a particle size of 1 – 2 mm and harvested in different regions of Ukraine in the mass fruiting phase in October-November 2020 were used. The quantitative determination of polyphenols and tannins was performed using the spectrophotometric method at a wavelength of 760 nm calculated with reference to pyrogallol and dried substance. The total amount of hydroxycinnamic acids was determined according to the method of the SPhU (State Pharmacopoeia of Ukraine) 2.0 described in the monograph “Kidney TeaN” calculated with reference to rosemary acid. The total amount of organic acids was determined by the titrimetric method according to the method of the monograph of the SPhU 2.1 “Rose hipsN” calculated with reference to malic acid.Results and discussion. The quantitative content of polyphenols (calculated with reference to pyrogallol and dried substance) in batches of Viburnum opulus fruits varied by about 1.4 times from 1.74 ± 0.01 % to 2.36 ± 0.01 %. According to the results obtained, the quantitative content of tannins (calculated with reference to pyrogallol and dried substance) in batches of Viburnum opulus fruits varied by 1.7 times from 0.73 ± 0.01 % to 1.23 ± 0.01 %. The quantitative content of the total amount of hydroxycinnamic acids calculated with reference to rosemary acid in batches of Viburnum opulus fruits ranged by 1.2 times from 3.96 ± 0.01 % to 4.73 ± 0.01 %. The quantitative content of the total amount of organic acids calculated with reference to malic acid in batches of Viburnum opulus fruits fluctuated more than 1.3 times from 6.80 ± 0.01 % to 9.08 ± 0.01 %.Conclusions. The quantitative content of the main groups of biologically active substances has been determined in 6 batches of Viburnum opulus fruits harvested in different regions of Ukraine using pharmacopoeial methods: polyphenols (varied by 1.4 times), tannins (varied by 1.7 times), the total amount of hydroxycinnamic (varied by 1.2 times), and the total amount of organic acids (varied by 1.3 times) calculated with reference to dried substance. The content of the groups of biologically active substances in batches of Viburnum opulus fruits slightly correlates with the place of the raw material harvesting. Thus, the selected methods of the SPhU 2.0 are quite suitable for determining the quantitative content of polyphenols, tannins and of the total amount of hydroxycinnamic and organic acids in batches of Viburnum opulus fruits; they can be used in further studies to standardize the raw material.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90326843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The allelopathic activity of water-soluble biologically active substances from Hyssopus officinalis L. of Marquis varieties and their effect on the root growth of Lepidium sativum L.","authors":"Yevheniia S. Tkachova, Mychailo I. Fedorchuk, O. Kovalenko","doi":"10.24959/ophcj.22.253471","DOIUrl":"https://doi.org/10.24959/ophcj.22.253471","url":null,"abstract":"Aim. To study the effect of secretions of bioactive water-soluble compounds from leaves, stems, flowers, and the root system of Hyssopus officinalis L. on the root growth of the test sample (Lepidium sativum L.).Materials and methods. To determine the effect of biologically active water-soluble compounds released by hyssop plants, a series of biotests was conducted; the allelopathic activity of leaves, stems, and flowers of H. officinalis L. and its root system were determined. The preparation of extracts of physiologically active substances was carried out according to the method of A. M. Grodzinsky. The allelopathic effect of H. officinalis L. was assessed by the effect of the water extracts of various concentrations (100 %, 50 % and 10 %) on the root length of seedlings of L. sativum L. test objects. The inhibition index was determined by Williamson method.Results and discussion. According to the results of the research, it was found that the allelopathic activity of water-soluble compounds of common hyssop affected the germination and length of seed roots of L. sativum L. as it changed with the age of the plant :  in the first year of vegetation, the stimulating effect of aqueous solutions of hyssop on seed germination was observed, in the second year, the stimulating effect decreased, and in the third year of vegetation, the inhibitory effect on seed germination of the test object was observed. Thus, the index of the allelopathic activity also changed.Conclusions. It was found that the highest allelopathic activity of biologically active water-soluble compounds of root secretions, leaves, stems and flowers of H. officinalis L. was during the flowering phase in concentrations of 100 %, 50 % and 10 %, affecting the length of the roots of seedlings of L. sativum L. test objects. At the same time, the maximum stimulating effect on the length of the roots of the test object was in the variant using an aqueous extract of plant flowers of the second year of vegetation in a 10 % concentration. The use of aqueous solutions of plants of the third year of vegetation had an inhibitory effect on the root length of L. sativum L seedlings.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72845939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the enzymatic method for the quantitative determination of dequalinium chloride in lozenges","authors":"M. Blazheyevskіy, O. Koval’ska","doi":"10.24959/ophcj.22.252499","DOIUrl":"https://doi.org/10.24959/ophcj.22.252499","url":null,"abstract":"Aim. To develop a new kinetic spectrophotometric enzymatic method suitable for the quantitative determination of dequalinium chloride in lozenges.Materials and methods. An enzymatic kinetic spectrophotometric method for the quantitative determination of dequalinium chloride in lozenges  has been proposed. It is based on the ability of dequalinium chloride to inhibit the enzymatic hydrolysis reaction of acetylcholine by cholinesterase in the presence of the acetylcholine (AСh) excess and H2O2. The degree of inhibition was determined by the kinetic method using two conjugated reactions: ACh perhydrolysis (interaction with an excess of hydrogen peroxide) followed by oxidation with the peroxyacid formed. Peracetic acid formed in situ by the reaction between unreacted ACh and H2O2 interacts with p-phenetidine forming a product, which absorbs at λmax = 354 nm, in the phosphate buffer solution with pH 8.3 at room temperature.Results and discussion. The linear dependence of the calibration graph for the quantitative determination of dequalinium chloride was in the concentration range of 0.2 – 0.8 μg mL–1 (r = 0.999). LOD and LOQ were 0.01 × 10–6 and 0.03 × 10–6 mol L–1, respectively. For the quantitative determination of dequalinium chloride in lozenges, RSD ≤ 2.65 % (accuracy, δ = -1.10…+1.78 %).Conclusions. A new enzymatic kinetic spectrophotometric method has been developed, and its applicability to the quantitative determination of dequalinium chloride in lozenges has been shown. It does not require a complicated treatment of the analyte and a tedious extraction procedure. The method proposed is sensitive enough to determine a small amount of the active pharmaceutical ingredient. These advantages encourage the application of the method proposed in routine quality control of the drugs studied in analytical laboratories.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77657072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative study of the effect of phenothiazine derivatives and their S-oxides on cholinesterase investigated by a new kinetic spectrophotometric method","authors":"Vladyslav Kovalenko, M. Blazheyevskiy, S. Merzlikin","doi":"10.24959/ophcj.22.252351","DOIUrl":"https://doi.org/10.24959/ophcj.22.252351","url":null,"abstract":"Aim. To develop a new kinetic spectrophotometric method for determining acetylcholinesterase (AChE) inhibitors – phenothiazine antipsychotic drugs (PhT) and their sulfoxide metabolites (S-oxides) without adding an exogenous catalyst to obtain a chromogenic agent.Materials and methods. The bases of S-oxides of promethazine (PMZ), chlorpromazine (CPM) and thioridazine (THZ) were obtained by oxidizing the corresponding PhT hydrochlorides with diperoxyadipic acid. The structure of the S-oxides of the corresponding PhT synthesized was proven by melting points, spectral characteristics (1H NMR and IR methods) and oscillopolarography results. 1H NMR spectra were recorded on a Varian XL-200 spectrometer. IR spectra were recorded within the range of 4000-400 cm–1 on a SPECORD M-80 spectrometer (Zeiss, Jena, Germany). To register polarograms, a “PO 03 CLA” oscillopolarograph with a three-electrode cell was used. The purity of S-oxides was determined by the high-performance liquid chromatography method on a Zorbax SB, C-18 (250 × 4.6) mm column. Measurements of absorbance of solutions were performed in a 1 cm cuvette on an Evolution 60S UV-Visible Thermo-Scientific Spectrophotometer (USA) (λ = 358 nm).Results and discussion. Acetylcholine (ACh) was found to mimic the activity of peroxidase; based on it, a spectrophotometric system containing ACh–H2O2–p-Ph for a sensitive and selective assessment of the AChE activity and determination of its inhibitors was developed. According to the plots of inhibition efficiency vs inhibitors concentration, the inhibiting ability of chlorpromazine, promethazine and thioridazine and their S-oxides was determined. The IC50 values of CPM, PMZ and THZ and their metabolites in relation to the AChE activity were estimated as 11 ng mL−1 (CPM) and 1.8 ng mL−1 (CPM S-oxide), 17 ng mL−1 (PMZ) and 2.5 ng mL−1 (PMZ S-oxide) and 27 ng mL−1 (THZ 2S,5S-dioxide). The results obtained indicate that S-oxides of the corresponding PhT are selective and potent inhibitors of AChE. The values of the inhibition efficiency obtained for S-oxides of PhT derivatives were an order of magnitude lower than those of the corresponding PhT derivatives.Conclusions. The spectrophotometric method proposed without the addition of other exogenous catalysts holds promise for the on-site determination of PhT antipsychotics and can be additionally used for sensory applications in areas related to environmental protection and food safety, as well as in the chemical-toxicological analysis.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76421996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New phosphorus-containing polycycles with a spiroamine group","authors":"Grygorii M. Koidan, A. Marchenko, Anastasiia M. Hurieva, Aleksandr M. Kostyuk","doi":"10.24959/ophcj.22.252844","DOIUrl":"https://doi.org/10.24959/ophcj.22.252844","url":null,"abstract":"Aim. To synthesize hexahydrospiro[cyclopropane-1,10’-pyrido[1,2-c]quinazoline] and 2-λ5-benzo[f][1,4,2]diazaphosphepine derivatives – new N-P containing heterocyclic compounds with the 6-azaspiro[2.5]octane fragment.Results and discussion. A new analog of the powerful electrophilic reagent – “Alder dimer” ‒ was obtained from the interaction of triflic anhydride and spiro(4-cyclopropane) piperidinyl formamide, and further used to synthesize new Nʹ-PV- and PIII-substituted Νʹ-phenyl, Νʹʹ-hexahydro(azaspiro)octylformamidinium salts – precursors of acyclic N-phosphorylated diamino carbenes with a spiroamine group. It has been shown that acyclic N-phosphorylated diaminocarbenes are transient species affording various products. The structure of the final product is primarily determined by nature of the phosphorus-bearing substituent, namely a phosphoryl or phosphino-group. N-PV-substituted carbene undergoes a 1,2-phosphorus shift with the formation of (selenophosphoryl)formamidine in a high yield. For N-PIII-substituted carbene a compatible 1,3-H shift also occurs with the formation of an intermediate azomethine ylide converted into a new heterocyclic system – hexahydrospirocyclopropane -1,10’-pyrido[1,2-c]quinazoline. Under the action of acid an unexpected further expansion of the 6-member ring occurs with the formation of a diazepine derivative.Experimental part. The reaction of Alder reagent with N-PV-seleno phosphoryl arylamides afforded N-phosphorus substituted formamidinium salts, which are easily reduced to PIII analogues. In addition to the corresponding formamidines, the new N-phosphorylated spiroamine-containing polycyclic system was isolated from the reaction mixture formed by the deprotonation of such salts with a strong non-nucleophilic base.Conclusions. The Alder reagent approach allows synthesizing precursors of acyclic formamidine carbenes with the spiroamine group. Such carbenes are unstable. By converting these compounds N-PIII-substituted tetrahydropyrimidine and diazaphosphepine derivatives with the 6-azaspiro[2.5]octane fragment have been obtained for the first time.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"55 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91508930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The synthesis and the anticonvulsant activity screening of new 5-substituted 2-imino-4-thiazolidinone derivatives","authors":"Ivan A. Sydorenko, Marija V. Mishchenko, S. Shtrygol’, Andriy V. Lozynskyy, I. I. Soronovych, S. Holota, R. Lesyk","doi":"10.24959/ophcj.22.248784","DOIUrl":"https://doi.org/10.24959/ophcj.22.248784","url":null,"abstract":"Aim. To synthesize 5-ene-4-thiazolidinones containing heterocyclic rings in the molecule as potential anticonvulsants, and screen their anticonvulsant activity on a model of pentylenetetrazole (PTZ) seizures.Results and discussion. A straightforward and convenient synthesis of novel 5-ene-derivatives of thiazol/oxazole-bearing 4-thiazolidinones as possible anticonvulsant agents was performed. Compounds were characterized using methods of spectral analysis (1H NMR and LC-MS). 5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde underwent the aminolysis on a chlorine atom by a molecule of monoethanolamine (MEA) in the Knoevenagel reaction with thiazole/oxazole-bearing 4-thiazolidinones. The preliminary screening of the anticonvulsant activity was performed for the compounds synthesized on the model of PTZ-induced seizures, and active derivatives were identified.Experimental part. Commercially available 2-aminothiazole and 5-methylisoxazol-3-amine were used as starting compounds for the synthesis of 2-chloro-N-(hetaryl)acetamides. The latter were transformed into thiazole/oxazole-bearing 4-thiazolidinones by the treatment with ammonium isothiocyanate. Modification at C5 position of the heterocycles synthesized was performed by the Knoevenagel reaction with aromatic/heteroaromatic aldehydes and MEA as a catalyst (either equimolar or 0.1 mol% amount) in the ethanol medium. The structure of novel derivatives was confirmed by 1H NMR and LC-MS spectra. The anticonvulsant activity of all derivatives synthesized was studied in vivo on the model of PTZ-induced seizures. Latency of the seizures, the number of clonic-tonic seizures in one mouse, the percent of animals with clonic and tonic seizures, the duration of the seizure period, and the lifetime of the animals before death were evaluated and calculated.Conclusions. The results obtained are promising for further design of potential anticonvulsants among oxazole-bearing 4-thiazolidones with the possible mechanism of the anticonvulsant action through the GABA-ergic impact and inhibition of the prostaglandin and leukotriene synthesis.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81317563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}