Home Microwave-assisted reactions: Efficient and versatile one-step synthesis of 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones under controlled microwave heating
Article Open Access

Microwave-assisted reactions: Efficient and versatile one-step synthesis of 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones under controlled microwave heating

  • Ramadan Ahmed Mekheimer , Alaa M. Hayallah , Moustafa Sherief Moustafa , Saleh Mohammed Al-Mousawi EMAIL logo , Mohamed Abd-Elmonem , Sara M. Mostafa , Fatma A. Abo Elsoud and Kamal Usef Sadek EMAIL logo
Published/Copyright: March 12, 2021
Download Article (PDF)
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Green Processing and Synthesis
From the journal Green Processing and Synthesis Volume 10 Issue 1

Abstract

We report herein a simple and efficient one-step synthesis of 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones via reaction of 1,3-dimethyl-5,6-diaminouracil 1 with activated double bond systems 2 assisted by controlled microwave irradiation. The obtained heterocycles are privileged biologically relevant scaffolds.

Graphical abstract

A green, simple one-pot microwave-assisted synthesis of xanthines and pyrimidopetridines was developed with a high EcoScale and yields.

Keywords: 8-substituted xanthines; pyrimidopetridines; 5,6-diaminouracil; green synthesis

1 Introduction

Uracil derivatives are interesting heterocycles which possess a wide spectrum of biological and pharmaceutical importance [1,2,3,4,5,6]. Among uracil derivatives, xanthines, pteridines, and pyrimidopteridines have attracted great attention for their unique promising biological activities. Polyfunctionally substituted xanthines are privileged heterocycles acting as adenosine receptor antagonists via four different specific G protein-coupled receptors (A1, A2A, A2B, A3) [7,8]. Activity of such receptors proceeds via inhibition or stimulation of adenylate cyclase [9,10,11,12]. Although nature offers the necessary needs for human being, naturally occurring xanthines (e.g. caffeine, theophylline) (Figure 1) are weak non-selective alpha 2D-adrenoceptors antagonists [13,14]. It is well documented that replacing the hydrogen atom at C-8 in xanthine with a large substituent and a suitable N-substitution resulted in increasing both affinity and selectivity toward ARs as antagonists [15]. Xanthines have shown a wide range of bioactivities that include treatment of bronchial asthma [16], cardiovascular problems [17], anticancer and anticancer adjuvants [18,19], kidney protectives, anti-fibrotic, antiglaucoma, and neuroprotective agents [20,21], as well as various biological activities [22].

Figure 1 Caffeine and theophylline as xanthine derivatives.
Figure 1

Caffeine and theophylline as xanthine derivatives.

Naturally occurring or synthesized pteridine derivatives have structural affinity to coenzymes and ability of chemical transformations [23]. They have been reported to possess a wide range of biological activities such as anti-fungal [24], anti-microbial [25], anti-allergic [26], immune-suppressive [27], anti-inflammatory [28], anti-tumor [29], antiproliferative [30], and anti-bacterial [31]. Moreover, several naturally occurring pteridines act as pigments, vitamins, and alkaloids [24,32]. Examples of biologically active xanthines and pteridines are illustrated in Figure 2.

Figure 2 Biologically active xanthines and pteridines.
Figure 2

Biologically active xanthines and pteridines.

Despite wide pharmaceutical applications and belongingness to purine family, xanthine-based research has not taken up full pace resulting in very few synthesized xanthine-based molecules. The most prominent reason for this is unfavorable synthesis methodologies such as ring closure synthetic mechanism and classical condensation route for the generation of new derivatives [12,33,34,35,36].

A number of synthetic routes for the synthesis of 8-substituted xanthines have focused on a two-step protocol through the reaction of N-mono or dialkylated 5,6-diaminouracil with aldehydes in EtOH/AcOH under reflux for several hours and subsequent oxidative cyclization of the formed imines[5-(arylidene or alkylidene-amino)-6-aminouracil] precursors utilizing a variety of catalysts such as SOCl2 or FeCl3 under refluxing conditions from 12 h to 2 days, meta-chloroperoxybenzoic acid in MeOH or (bromodimethyl)sulfonium bromide (BDMS) [9,37,38,39].

An alternative route for the synthesis of 8-substituted xanthines has been developed that relied on the coupling of diaminouracil derivative with acids utilizing several reagents such as 3-(3-dimethylaminopropyl)-carbodiimide hydrochloride [37], (1-[1-(cyano-2-ethoxy-2-oxoethylideneaminooxyl)-dimethylamino-morpholino]-methylene)methanaminium hexafluorophosphate [15], and subsequent cyclization of the formed 6-amino-5-carboxamidouracil. Several reagents for cyclization step were used such as sodium hydroxide [37] and hexamethyldisilazane in the presence of ammonium sulfate and heating under reflux [38]. Another route involving the activation of the carboxylic acid by conversion to acid chloride was alternatively used, but it possesses several drawbacks such as long reaction times for amide formation, moderate yields, less stability of acid chlorides, and an additional step for conversion of acids to acid chlorides utilizing non-environmentally hazardous chlorinating agents [40].

A one-step synthesis of 8-substituted xanthines has been developed via stoichiometric coupling of aldehydes with 1,3-diaminouracil in acetonitrile catalyzed by 10 mol% of BDMS and heating under reflux for 5 h [39].

A less extensively studied synthesis of 8-substituted xanthine scaffolds involves the reaction of 8-bromoxanthine derivatives with various nucleophiles [41,42,43,44]. Palladium-catalyzed direct alkenylation of 8-unsubstituted xanthine has been recently investigated by Liang et al. [45] utilizing bulky (2-bromoethene-1,1,2-triaryl)tribenzene and as a result of low efficiency of reaction it proceeds only in high boiling point solvent as DMF or diethylene glycol dimethyl ester (diglyme) at 150°C with moderate yields.

To the best of our knowledge, a carful inspection of literature reports has revealed a very few reports for the synthesis of 1,3-dialkyl substituted pteridine derivatives. In 1954, Blicke and Godt [46] have developed the synthesis of 1,3-dimethyllumazine derivatives via the reaction of 1,3-dimethyl-5,6-diaminouracil with glyoxal, oxalic acid, diacetal, and benzil in 30%, 58%, 64%, and 80% yields. Moreover, the corresponding 1,3-dimethyl-7-aminolumazine could be synthesized through reaction of diaminouracil derivatives with formaldehyde and hydrocyanic acid followed by treatment of the produced 5-cyanomethylamino derivative with KOH/MeOH and H2O2. Not very recently, El-Sabbagh et al. [47] have reported a chemoselective reaction of 6-amino-1,3-dimethyl-5-(substituted methylidene)aminouracils with ortho esters. With triethyl orthoformate, the corresponding 6-substituted pteridines were the only isolable products, however, with triethyl orthoacetate or triethyl orthobenzoate, the corresponding xanthines were obtained.

Disadvantage aspects of such protocols are the use of external oxidants, hazardous solvents, expensive catalysts, high temperature, long reaction times, by-product formation, and low yields.

Recently, a convenient one-step synthesis of 8-substituted xanthines has been developed by Kaushik et al. [12] that relied on the reaction of 1,3-dimethyl-5,6-diaminouracil with aryl/cycloaryl/heteroaryl aldehydes in CH3CN/H2O (9:1) promoted with N-bromosuccinimide utilizing catalytic amount of 2,2′-azoisobutyronitrile at ambient temperature.

Taking into consideration such disadvantages and in continuation to our efforts to perform green and efficient one-pot synthesis of biologically relevant heterocycles assisted by controlled microwave heating [48,49,50,51,52], we have developed a one-pot synthesis of 8-substituted xanthines and substituted pyrimidopteridines via reaction of 1,3-dimethyl-5,6-diaminouracil with a variety of electrophilic reagents in pyridine under controlled microwave heating. It has been reported that factors modulating synthetic selectivity are temperature, solvent, catalyst, and type of reaction control [53,54,55,56,57].

2 Materials and methods

All chemicals were purchased from Merck or Aldrich Companies. The 1H NMR (600 MHz) and 13C NMR (150 MHz) were run in a Bruker DPX instrument (δ ppm). Mass spectra were measured by using VG Autospec Q MS 30 and MS 9 (AEI) spectrometer, with EI (70 eV) mode. Melting points were recorded in a Gallenkamp melting point apparatus and are uncorrected. All reactions were monitored by thin layer chromatography (TLC) with 1:1 ethyl acetate/petroleum ether as an eluent and were carried out until starting materials were completely consumed.

2.1 General procedure for the reaction of 1,3-dimethyl-5,6-diaminouracil 1 with arylidene malononitriles and β-nitrostyrenes 2a–e

Equimolar amounts of 1 (1 mmol) and 2 (1 mmol) in pyridine (10 mL) were heated under reflux in a Milestone Microwave Labstation at 120°C for 20 min. The solvent was removed under reduced pressure, and the solid product was isolated by filtration and recrystallized from ethanol to afford analytically pure samples.

2.2 General procedure for the reaction of 1,3-dimethyl-5,6-diaminouracil 1 with phenyl isothiocyanate 6

Equimolar amounts of 1 (1 mmol) and 6 (1 mmol) in acetone (10 mL) were heated under reflux at 70°C under microwave heating for 5 min. The reaction product isolated upon cooling to room temperature was collected by filtration and recrystallized from ethanol.

2.3 General procedure for the reaction of 1,3-dimethyl-5,6-diaminouracil 1 with enaminones 9a–c

Equimolar amounts of 1 (1 mmol) and 9 (1 mmol) in pyridine (10 mL) were heated under reflux in a Milestone Microwave Labstation at 120°C for 20 min. The solvent was removed under reduced pressure, and the solid product was isolated by filtration and recrystallized from ethanol to afford 11 and the rest quantity from DMF to afford 12.

3 Results and discussion

With the initial aim of optimizing the reaction conditions, we began our study by treating 1,3-dimethyl-5,6-diaminouracil 1 with 2-(4-methoxybenzylidene)malononitrile 2a. Under catalyst-free conditions, the reaction did not ensue when water, ethanol, acetonitrile, and dioxane were used as solvents even under reflux for prolonged heating, indicating the crucial role of the catalyst in this reaction. Pyridine was found to be the best reaction medium for this reaction as it has dual role as a solvent and a basic catalyst, which reduces the number of synthetic steps. Thus, heating under reflux the aforementioned mixture in pyridine for 3 h led to the formation of product 3a in 60% yield. In order to increase energy efficiency, the reaction was promoted by microwave irradiation at 120°C for 20 min. We are delighted to obtain 3a in 92% yield (Scheme 1). The structure of 3a could be established based on analytical and spectral data. Mass spectrum of 3a showed [M+] peak at 286.01 (100%). The IR spectrum revealed the absence of NH2 and CN functions. 1H NMR showed a broad singlet at δ = 13.56 ppm due to purine NH proton and two doublets at δ = 8.08 and 7.06 ppm, which were assigned to four aromatic protons, in addition to three singlet signals at δ = 3.32, 3.48, and 3.82 ppm for two N-methyl groups and one methoxy group, respectively. 13C NMR spectrum was compatible with the structure of the reaction product 3a. With this promising result in hand, we investigated the influence of the aryl substrate in arylidene malononitrile 2 on the nature of the reaction product and its rate of formation. Thus, the reaction of 1 with 2b–c under the same experimental reaction conditions afforded the corresponding 8-substituted xanthines 3b–c, in high yields, irrespective of the aryl substrate. Although it has been previously reported [58] that the reaction of 1 with arylidene malononitriles afforded the corresponding pyrimidodiazepines, this is not favored in our case.

Scheme 1 Synthesis of 8-substituted xanthines.
Scheme 1

Synthesis of 8-substituted xanthines.

In order to explore the generality of such a protocol, the reaction of 1 with diversity activated double bond systems was examined. Thus, reaction of 1 with β-nitrostyrene 2d and 2e, under the same experimental conditions, yielded solid products which confirmed to be 3a and 3c, respectively, based on analytical and spectral data.

The reaction was proposed to proceed via Michael addition of electron-rich (C5-NH2) in 1 to the activated double bond in 2a–e producing Michael adduct 4 followed by cyclization through nucleophilic attack of (C6-NH2) lone pair to the positively charged (C1) carbon and malononitrile or nitric acid elimination – as cyclization by elimination is more thermodynamically feasible – and subsequent aromatization (Scheme 1). In support of such mechanism, we performed the reaction of 1 with benzaldehyde under the same experimental reaction conditions, and the corresponding Schiff base was the only isolable product.

We extended the scope of our study to the reaction of 1 with phenyl isothiocyanate 6 and the reaction was promoted by microwave heating in acetone at 70°C for 5 min. A product of molecular formula C13H13N5O2 was obtained and confirmed to be the corresponding xanthine derivative 8. The structure proposed for 8 was established based on analytical and spectral data and detection of H2S liberation (Scheme 1).

On the other hand, the reaction of 1 with enaminones 9 proceeded via unexpected route. Thus, as example, the reaction of 1 with 9a in pyridine promoted by microwave irradiation afforded two reaction products 11 and 12a in 1:4 molar ratios. Compound 11 showed [M+] peak at 303.99 (100%). 1H NMR revealed two singlet signals at δ = 3.59 and 3.32 ppm integrated for four N-methyl functions. 13C NMR revealed four carbonyl functions and four N-methyl groups. Based on these data, the corresponding 1,3,7,9-tetramethylpyrimido[4,5-g]pteridine-2,4,6,8-(1H,3H,7H,9H)-tetraone was established for the product. Compound 11 was suggested to be formed through dimerization of 1 to 10 via elimination of ammonia followed by auto-oxidation, under these reaction conditions. However, the second isolated product 12a resulted from nucleophilic attack of the more reactive NH (no. 5) in 10 to the more electrophilic center in enaminone 9 with elimination of dimethylamine. It is worth mentioning that the formation of dimer 11 was hypothetically proposed previously by Teimouri et al. [59] upon refluxing 1 in EtOH/p-TSA (10 mol%). To the best of our knowledge, this is the first reported isolation of such compound 12 (Scheme 2).

Scheme 2 Synthesis of substituted pyrimidopteridine-2,4,6,8-tetraones.
Scheme 2

Synthesis of substituted pyrimidopteridine-2,4,6,8-tetraones.

To evaluate the greenness of the reaction, we estimated the EcoScale [60] for our protocol concerning the one-step synthesis of 8-substituted xanthines and compared with other recently reported synthetic methods (Table 1).

Table 1

Comparison of ecoscale of literature reported synthesis of xanthines

Procedure Reaction time Yield (%) Ecoscale
Traver et al. [41] 20 min 21 54
KO t Bu/THF/90°C/flow
Nagavelli et al. [42] 6–8 h 77 72.5
CuI/THF
Bashirova et al. [44] 90 min 91 86.5
KOH/H2O/EtOH
Liang et al. [43] 24 h 77 88.5
Pd2/dbal3 (5 mol%)
Nixantphos (10 mol)
t-BuONa (3 eq.)
Our protocol
Pyridine/MW (3a) 20 min 92 92
Pyridine/MW (3b) 20 min 90 90
Pyridine/MW (3c) 20 min 88 88
Acetone/MW (8) 5 min 88 88

4 Conclusion

In summary, the methods described above represent an efficient, simple, and convenient protocols for microwave assisted reaction for the synthesis of various 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones. In some cases, the isolation of the reaction intermediate shed further light as the mechanism of its formation.

Acknowledgement

K. U. Sadek is grateful to the Alexander von Humboldt Foundation for donation of a Milestone START Microwave Labstation. Saleh Al-Mousawi and Moustafa Sherief Moustafa are grateful to the Kuwait Foundation for the Advancement of Science, project number PR18-13SC-01, for supporting this work. Analytical facilities provided by Kuwait University GFS projects No. GS 01/03 and GS 03/08 are greatly appreciated.

  1. Research funding: This study was funded by Project no. PR18-13SC-01.

  2. Author contributions: Ramadan A. Mekheimer: visualization and methodology; Alaa M. Hayallah: methodology and resources; Moustafa M. Moustafa: formal analysis and data curation; Saleh M. Al-Mousawi: funding acquisition and resources; Mohamed Abd-Elmonem: writing – review and editing; Sara M. Mostafa: writing – review and editing; Fatma A. Abo-Elsoud: software and investigation; and Kamal U. Sadek: supervision and writing – original draft.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Supplementary information: The supplementary information file contains characterization data for compounds 3a, 3b, 3c, 8, 11, 12a, 12b, and 12c.

References

[1] Lewandowska M, Ruszkowski P, Baraniak D, Czarnecka A, Kleczewska N, Celewicz L. Synthesis of 3′-azido-2′,3′-dideoxy-5-fluorouridine phosphoramidates and evaluation of their anticancer activity. Eur J Med Chem. 2013;67:188–95.10.1016/j.ejmech.2013.06.047Search in Google Scholar

[2] Evdokimov NM, Van slambrouck S, Heffeter P, Tu L, Le Calvé B, Lamoral-Theys D, et al. Structural simplification of bioactive natural products with multicomponent synthesis. 3. Fused uracil-containing heterocycles as novel topoisomerase-targeting agents. J Med Chem. 2011;54(7):2012–21.10.1021/jm1009428Search in Google Scholar

[3] Solano JD, González-Sánchez I, Cerbón MA, Guzmán Á, Martínez-Urbina MA, Vilchis-Reyes MA, et al. The products of the reaction between 6-amine-1,3-dimethyl uracil and bis-chalcones induce cytotoxicity with massive vacuolation in HeLa cervical cancer cell line. Eur J Med Chem. 2013;60:350–9.10.1016/j.ejmech.2012.12.021Search in Google Scholar

[4] Sun L, Bera H, Chui WK. Synthesis of pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors of thymidine phosphorylase. Eur J Med Chem. 2013;65:1–11.10.1016/j.ejmech.2013.03.063Search in Google Scholar

[5] Tzioumaki N, Manta S, Tsoukala E, Johan VV, Liekens S, Komiotis D, et al. Synthesis and biological evaluation of unsaturated keto and exomethylene d-arabinopyranonucleoside analogs: novel 5-fluorouracil analogs that target thymidylate synthase. Eur J Med Chem. 2011;46(4):993–1005.10.1016/j.ejmech.2011.01.005Search in Google Scholar

[6] Illán-Cabeza NA, García-García AR, Martínez-Martos JM, Ramírez-Expósito MJ, Peña-Ruiz T, Moreno-Carretero MN. A potential antitumor agent, (6-amino-1-methyl-5-nitrosouracilato-N3)-triphenylphosphine-gold(I): structural studies and in vivo biological effects against experimental glioma. Eur J Med Chem. 2013;64:260–72.10.1016/j.ejmech.2013.03.067Search in Google Scholar

[7] Müller CE, Jacobson KA. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta Biomembr. 2011;1808(5):1290–308.10.1016/j.bbamem.2010.12.017Search in Google Scholar

[8] Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE. International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors – an update. Pharmacol Rev. 2011;63(1):1–34.10.1124/pr.110.003285Search in Google Scholar

[9] Daly JW. Adenosine receptors: targets for future drugs. J Med Chem. 1982;25(3):197–207.10.1021/jm00345a001Search in Google Scholar

[10] Meade CJ, Dumont I, Worrall L. Why do asthmatic subjects respond so strongly to inhaled adenosine? Life Sci. 2001;69(11):1225–40.10.1016/S0024-3205(01)01231-0Search in Google Scholar

[11] Feoktistov I, Biaggioni I, Polosa R, Holgate ST. Adenosine A2B receptors: a novel therapeutic target in asthma? Trends Pharmacol Sci. 1998;19(4):148–53.10.1016/S0165-6147(98)01179-1Search in Google Scholar

[12] Bandyopadhyay P, Agrawal SK, Sathe M, Sharma P, Kaushik MP. A facile and rapid one-step synthesis of 8-substituted xanthine derivatives via tandem ring closure at room temperature. Tetrahedron. 2012;68(20):3822–7.10.1016/j.tet.2012.03.050Search in Google Scholar

[13] Nieber K. The impact of coffee on health. Planta Med. 2017;83(16):1256–63.10.1055/s-0043-115007Search in Google Scholar PubMed

[14] Oñatibia-Astibia A, Franco R, Martínez-Pinilla E. Health benefits of methylxanthines in neurodegenerative diseases. Mol Nutr Food Res. 2017;61(6):1600670.10.1002/mnfr.201600670Search in Google Scholar PubMed

[15] Marx D, Wingen LM, Schnakenburg G, Müller CE, Scholz MS. Fast, efficient, and versatile synthesis of 6-amino-5-carboxamidouracils as precursors for 8-substituted xanthines. Front Chem. 2019;7:56.10.3389/fchem.2019.00056Search in Google Scholar PubMed PubMed Central

[16] Roy UK, Pal M, Datta S, Harlalka S. Has oxidative stress any role on mechanisms of aminophylline – induced seizures? An animal study. Kathmandu Univ Med J. 2015;12:269–74.10.3126/kumj.v12i4.13733Search in Google Scholar PubMed

[17] Rutherford JD, Vatner SF, Braunwald E. Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs. Circulation. 1981;63(2):378–87.10.1161/01.CIR.63.2.378Search in Google Scholar PubMed

[18] Abou-Zied HA, Youssif BGM, Mohamed MFA, Hayallah AM, Abdel-Aziz M. EGFR inhibitors and apoptotic inducers: design, synthesis, anticancer activity and docking studies of novel xanthine derivatives carrying chalcone moiety as hybrid molecules. Bioorg Chem. 2019;89:102997.10.1016/j.bioorg.2019.102997Search in Google Scholar PubMed

[19] Hisham M, Youssif BGM, Osman EEA, Hayallah AM, Abdel-Aziz M. Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents. Eur J Med Chem. 2019;176:117–28.10.1016/j.ejmech.2019.05.015Search in Google Scholar PubMed

[20] van den Berge M, Hylkema MN, Versluis M, Postma DS. Role of adenosine receptors in the treatment of asthma and chronic obstructive pulmonary disease. Drugs R D. 2007;8(1):13–23.10.2165/00126839-200708010-00002Search in Google Scholar PubMed

[21] Akkari R, Burbiel J, Hockemeyer J, Muller C. Recent progress in the development of adenosine receptor ligands as antiinflammatory drugs. Curr Top Med Chem. 2006;6(13):1375–99.10.2174/15680266106061375Search in Google Scholar

[22] Singh N, Shreshtha AK, Thakur MS, Patra S. Xanthine scaffold: scope and potential in drug development. Heliyon. 2018;4(10):e00829.10.1016/j.heliyon.2018.e00829Search in Google Scholar

[23] Avendaño C, Menéndez JC. Medicinal chemistry of anticancer drugs. Medicinal chemistry of anticancer drugs. 2nd edn. Amsterdam, Netherlands: Elsevier; 2015.10.1016/B978-0-444-62649-3.00013-2Search in Google Scholar

[24] Voet D, Voet JG. Biochemistry. 3rd edn. New York: John Wiley and Sons; 2004.Search in Google Scholar

[25] Al-Diksin AA, Al-Amood HK. Synthesis and biological activity study of some new pteridine derivatives. Res J Pharm Biol Chem Sci. 2015;6(6):899–904.Search in Google Scholar

[26] Ferrand G, Dumas H, Depin JC, Quentin Y. Synthesis and potential antiallergic activity of new pteridinones and related compounds. Eur J Med Chem. 1996;31(4):273–80.10.1016/0223-5234(96)80364-3Search in Google Scholar

[27] Kokuryo Y, Nakatani T, Kakinuma M, Kabaki M, Kawata K, Kugimiya A, et al. New γ-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immunosuppressive activity. Eur J Med Chem. 2000;35(5):529–34.10.1016/S0223-5234(00)00147-1Search in Google Scholar

[28] Pontiki E, Hadjipavlou-Litina D, Patsilinakos A, Tran TM, Marson CM. Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of lipoxygenase that can possess anti-inflammatory properties. Future Med Chem. 2015;7(14):1937–51.10.4155/fmc.15.104Search in Google Scholar PubMed PubMed Central

[29] Zhang Z, Wu J, Ran F, Guo Y, Tian R, Zhou S, et al. Novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives as dihydrofolate inhibitor: design, synthesis and antifolate activity. Eur J Med Chem. 2009;44(2):764–71.10.1016/j.ejmech.2008.04.017Search in Google Scholar PubMed

[30] Li Z-H, Zhao T-Q, Liu X-Q, Zhao B, Wang C, Geng P-F, et al. Synthesis and preliminary antiproliferative activity of new pteridin-7(8H)-one derivatives. Eur J Med Chem. 2018;143:1396–405.10.1016/j.ejmech.2017.10.037Search in Google Scholar PubMed

[31] Reynolds RC, Srivastava S, Ross LJ, Suling WJ, White EL. A new 2-carbamoyl pteridine that inhibits mycobacterial FtsZ. Bioorg Med Chem Lett. 2004;14(12):3161–4.10.1016/j.bmcl.2004.04.012Search in Google Scholar PubMed

[32] Milstien S, Kapatos G, Levine RA, Shane B. Chemistry and biology of pteridines and folates. Proceedings of the 12th international symposium on pteridines and folates, national institutes of health, Bethesda, Maryland. New York: Springer US; 2002.10.1007/978-1-4615-0945-5Search in Google Scholar

[33] Sakai R, Konno K, Yamamoto Y, Sanae F, Takagi K, Hasegawa T, et al. Effects of alkyl substitutions of xanthine skeleton on bronchodilation. J Med Chem. 1992;35(22):4039–44.10.1021/jm00100a008Search in Google Scholar PubMed

[34] Kim D, Jun H, Lee H, Hong SS, Hong S. Development of new fluorescent xanthines as kinase inhibitors. Org Lett. 2010;12(6):1212–5.10.1021/ol100011nSearch in Google Scholar PubMed

[35] Chen Y, Wang B, Guo Y, Zhou Y, Pan L, Xiong L, et al. Synthesis and biological activities of novel methyl xanthine derivatives. Chem Res Chin Univ. 2014;30(1):98–102.10.1007/s40242-014-3173-4Search in Google Scholar

[36] Lee D, Lee S, Liu KH, Bae JS, Baek DJ, Lee T. Solid-phase synthesis of 1,3,7,8-tetrasubstituted xanthine derivatives on traceless solid support. ACS Comb Sci. 2016;18(1):70–4.10.1021/acscombsci.5b00148Search in Google Scholar PubMed

[37] Holschbach MH, Bier D, Sihver W, Schulze A. Neumaier B. synthesis and pharmacological evaluation of identified and putative metabolites of the A1 adenosine receptor antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX). ChemMedChem. 2017;12(10):770–84.10.1002/cmdc.201600592Search in Google Scholar PubMed

[38] Hayallah AM, Sandoval-Ramírez J, Reith U, Schobert U, Preiss B, Schumacher B, et al. 1,8-disubstituted xanthine derivatives:  synthesis of potent A2B-selective adenosine receptor antagonists. J Med Chem. 2002;45(7):1500–10.10.1021/jm011049ySearch in Google Scholar PubMed

[39] LaBeaume P, Dong M, Sitkovsky M, Jones EV, Thomas R, Sadler S, et al. An efficient route to xanthine based A2A adenosine receptor antagonists and functional derivatives. Org Biomol Chem. 2010;8(18):4155–7.10.1039/c003382kSearch in Google Scholar PubMed

[40] Hockemeyr J, Burbeil JC, Muller CE. Multigram-scale syntheses, stability and photoreactions of A2A adenosine receptor antagonists with 8-styrylxanthine structure: Potential drugs for Parkinson’s disease. J Org Chem. 2004;69(10):3308–18.10.1021/jo0358574Search in Google Scholar PubMed

[41] Czechtzky E, Dedo J, Desai B, Dixon K, Farrant E, Feng Q, et al. Integrated synthesis and testing of substituted xanthine based DPP4 inhibitors: application to drug discovery. ACS Med Chem Lett. 2013;4(8):768–72.10.1021/ml400171bSearch in Google Scholar PubMed PubMed Central

[42] Narsimah S, Battula KS, Ravinder M, Reddy YN, Nagavelli VR. Design synthesis and biological evaluation of novel 1,2,3-triazole-based xanthine derivatives as DPP-4 inhibitors. J Chem Sci. 2020;54(9):891–6.10.1007/s12039-020-1760-0Search in Google Scholar

[43] Liang Y, Zhang X, MacMillan DWC. Decarboxylative Sp3 C-N coupling via dual copper and photoredox catalysis. Nature. 2018;5559(7712):83–8.10.1038/s41586-018-0234-8Search in Google Scholar PubMed PubMed Central

[44] Khaliullin FA, Mamatov ZK, Timirkhanova GA, Bashirova LI. Synthesis, antiaggregant, and antioxidant activity of 2-([1-iso-butyl-3-methyl-7-(thietanyl-3)xanthine-8-yl]thio) acetic acid salts. Pharm Chem J. 2020;54(9):891–6.10.1007/s11094-020-02293-wSearch in Google Scholar

[45] Yao Y-X, Fang D-M, Gao F, Liang X-X. Room temperature palladium catalyzed direct 2-alkenylation of azole derivatives with Alkenyl bromides. Tetrahedron Lett. 2019;60(1):68–71.10.1016/j.tetlet.2018.11.058Search in Google Scholar

[46] Blicke FF, Godt HC. Reactions of 1,3-dimethyl-5,6-diaminouracil. J Am Chem Soc. 1954;76(10):2798–800.10.1021/ja01639a058Search in Google Scholar

[47] El-Sabbagh OI, El-Sadek ME, El-Kalyoubi S, Ismail I. Synthesis, DNA binding and antiviral activity of new uracil, xanthine, and pteridine derivatives. Arch Pharm. 2007;340(1):26–31.10.1002/ardp.200600149Search in Google Scholar PubMed

[48] Sadek KU, Mekheimer RA, Mohamed TM, Moustafa MS, Elnagdi MH. Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating. Beilstein J Org Chem. 2012;8:18–24.10.3762/bjoc.8.3Search in Google Scholar PubMed PubMed Central

[49] Hameed AA, Ahmed EK, Fattah AAA, Andrade CKZ, Sadek KU. Green and efficient synthesis of polyfunctionally substituted cinnolines under controlled microwave irradiation. Res Chem Intermed. 2017;43(10):5523–33.10.1007/s11164-017-2944-1Search in Google Scholar

[50] Dyab AKF, Sadek KU. Microwave assisted one-pot green synthesis of cinnoline derivatives inside natural sporopollenin microcapsules. RSC Adv. 2018;8(41):23241–51.10.1039/C8RA04195DSearch in Google Scholar

[51] Sadek KU, Shaker RM, Elrady MA, Elnagdi MH. A novel method for the synthesis of polysubstituted diaminobenzonitrile derivatives using controlled microwave heating. Tetrahedron Lett. 2010;51(48):6319–21.10.1016/j.tetlet.2010.09.114Search in Google Scholar

[52] El Latif FMA, Barsy MA, Aref AM, Sadek KU. Microwave-assisted reactions: part 2 one-pot synthesis of pyrimido-[1,2-a]pyrimidines. Green Chem. 2002;4(3):196–8.10.1039/b110723mSearch in Google Scholar

[53] Carey FA, Sundberg RJ. Advanced organic chemistry part A: structure and mechanisms. Advanced organic chemistry. 5th edn. New York: Springer; 2007. p. 1171.Search in Google Scholar

[54] Erkkilä A, Majander I, Pihko PM. Iminium catalysis. Chem Rev. 2007;107(12):5416–70.10.1021/cr068388pSearch in Google Scholar PubMed

[55] Laschat S, Becheanu A, Bell T, Baro A. Regioselectivity, stereoselectivity and catalysis in intermolecular Pauson-Khand reactions: teaching an old dog new tricks. Synlett. 2005;2005(17):2547–70.10.1055/s-2005-918922Search in Google Scholar

[56] Kappe CO. Controlled microwave heating in modern organic synthesis. Angew Chem Int Ed. 2004;43(46):6250–84.10.1002/anie.200400655Search in Google Scholar PubMed

[57] De la Hoz A, Díaz-Ortiz Á, Moreno A. Microwaves in organic synthesis. Thermal and non-thermal microwave effects. Chem Soc Rev. 2005;34(2):164–78.10.1039/B411438HSearch in Google Scholar

[58] El-Kalyoubi SA, Fayed EA, Abdel-Razek AS. One pot synthesis, antimicrobial and antioxidant activities of fused uracils: Pyrimidodiazepines, lumazines, triazolouracil and xanthines. Chem Cent J. 2017;11(1):1–13.10.1186/s13065-017-0294-0Search in Google Scholar

[59] Teimouri MB, Meydani A, Panji Z. A one-pot synthesis of 5-(1,3-dimethyl-2,6-dioxo-5-{[(1,e)-arylmethylene]amino}-1,2,3,6-tetrahydropyrimidin-4-yl)-1,3,7,9-tetramethyl-5,10-dihydropyrimido[5,4-g]pteridine-2,4,6,8(1 h ,3 h ,7 h ,9 h)-tetrone via a pseudo four-component domino reaction. Polycyclic Aromat Compd. 2019;39:1–14.10.1080/10406638.2019.1678182Search in Google Scholar

[60] Van Aken K, Strekowski L, Patiny L. EcoScale, a semi-quantitative tool to select an organic preparation based on economical and ecological parameters. Beilstein J Org Chem. 2006;2:3.10.1186/1860-5397-2-3Search in Google Scholar PubMed PubMed Central

Received: 2020-12-07
Revised: 2021-01-19
Accepted: 2021-01-26
Published Online: 2021-03-12

© 2021 Ramadan Ahmed Mekheimer et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. MW irradiation and ionic liquids as green tools in hydrolyses and alcoholyses
  3. Effect of CaO on catalytic combustion of semi-coke
  4. Studies of Penicillium species associated with blue mold disease of grapes and management through plant essential oils as non-hazardous botanical fungicides
  5. Development of leftover rice/gelatin interpenetrating polymer network films for food packaging
  6. Potent antibacterial action of phycosynthesized selenium nanoparticles using Spirulina platensis extract
  7. Green synthesized silver and copper nanoparticles induced changes in biomass parameters, secondary metabolites production, and antioxidant activity in callus cultures of Artemisia absinthium L.
  8. Gold nanoparticles from Celastrus hindsii and HAuCl4: Green synthesis, characteristics, and their cytotoxic effects on HeLa cells
  9. Green synthesis of silver nanoparticles using Tropaeolum majus: Phytochemical screening and antibacterial studies
  10. One-step preparation of metal-free phthalocyanine with controllable crystal form
  11. In vitro and in vivo applications of Euphorbia wallichii shoot extract-mediated gold nanospheres
  12. Fabrication of green ZnO nanoparticles using walnut leaf extract to develop an antibacterial film based on polyethylene–starch–ZnO NPs
  13. Preparation of Zn-MOFs by microwave-assisted ball milling for removal of tetracycline hydrochloride and Congo red from wastewater
  14. Feasibility of fly ash as fluxing agent in mid- and low-grade phosphate rock carbothermal reduction and its reaction kinetics
  15. Three combined pretreatments for reactive gasification feedstock from wet coffee grounds waste
  16. Biosynthesis and antioxidation of nano-selenium using lemon juice as a reducing agent
  17. Combustion and gasification characteristics of low-temperature pyrolytic semi-coke prepared through atmosphere rich in CH4 and H2
  18. Microwave-assisted reactions: Efficient and versatile one-step synthesis of 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones under controlled microwave heating
  19. New approach in process intensification based on subcritical water, as green solvent, in propolis oil in water nanoemulsion preparation
  20. Continuous sulfonation of hexadecylbenzene in a microreactor
  21. Synthesis, characterization, biological activities, and catalytic applications of alcoholic extract of saffron (Crocus sativus) flower stigma-based gold nanoparticles
  22. Foliar applications of plant-based titanium dioxide nanoparticles to improve agronomic and physiological attributes of wheat (Triticum aestivum L.) plants under salinity stress
  23. Simultaneous leaching of rare earth elements and phosphorus from a Chinese phosphate ore using H3PO4
  24. Silica extraction from bauxite reaction residue and synthesis water glass
  25. Metal–organic framework-derived nanoporous titanium dioxide–heteropoly acid composites and its application in esterification
  26. Highly Cr(vi)-tolerant Staphylococcus simulans assisting chromate evacuation from tannery effluent
  27. A green method for the preparation of phoxim based on high-boiling nitrite
  28. Silver nanoparticles elicited physiological, biochemical, and antioxidant modifications in rice plants to control Aspergillus flavus
  29. Mixed gel electrolytes: Synthesis, characterization, and gas release on PbSb electrode
  30. Supported on mesoporous silica nanospheres, molecularly imprinted polymer for selective adsorption of dichlorophen
  31. Synthesis of zeolite from fly ash and its adsorption of phosphorus in wastewater
  32. Development of a continuous PET depolymerization process as a basis for a back-to-monomer recycling method
  33. Green synthesis of ZnS nanoparticles and fabrication of ZnS–chitosan nanocomposites for the removal of Cr(vi) ion from wastewater
  34. Synthesis, surface modification, and characterization of Fe3O4@SiO2 core@shell nanostructure
  35. Antioxidant potential of bulk and nanoparticles of naringenin against cadmium-induced oxidative stress in Nile tilapia, Oreochromis niloticus
  36. Variability and improvement of optical and antimicrobial performances for CQDs/mesoporous SiO2/Ag NPs composites via in situ synthesis
  37. Green synthesis of silver nanoparticles: Characterization and its potential biomedical applications
  38. Green synthesis, characterization, and antimicrobial activity of silver nanoparticles prepared using Trigonella foenum-graecum L. leaves grown in Saudi Arabia
  39. Intensification process in thyme essential oil nanoemulsion preparation based on subcritical water as green solvent and six different emulsifiers
  40. Synthesis and biological activities of alcohol extract of black cumin seeds (Bunium persicum)-based gold nanoparticles and their catalytic applications
  41. Digera muricata (L.) Mart. mediated synthesis of antimicrobial and enzymatic inhibitory zinc oxide bionanoparticles
  42. Aqueous synthesis of Nb-modified SnO2 quantum dots for efficient photocatalytic degradation of polyethylene for in situ agricultural waste treatment
  43. Study on the effect of microwave roasting pretreatment on nickel extraction from nickel-containing residue using sulfuric acid
  44. Green nanotechnology synthesized silver nanoparticles: Characterization and testing its antibacterial activity
  45. Phyto-fabrication of selenium nanorods using extract of pomegranate rind wastes and their potentialities for inhibiting fish-borne pathogens
  46. Hydrophilic modification of PVDF membranes by in situ synthesis of nano-Ag with nano-ZrO2
  47. Paracrine study of adipose tissue-derived mesenchymal stem cells (ADMSCs) in a self-assembling nano-polypeptide hydrogel environment
  48. Study of the corrosion-inhibiting activity of the green materials of the Posidonia oceanica leaves’ ethanolic extract based on PVP in corrosive media (1 M of HCl)
  49. Callus-mediated biosynthesis of Ag and ZnO nanoparticles using aqueous callus extract of Cannabis sativa: Their cytotoxic potential and clinical potential against human pathogenic bacteria and fungi
  50. Ionic liquids as capping agents of silver nanoparticles. Part II: Antimicrobial and cytotoxic study
  51. CO2 hydrogenation to dimethyl ether over In2O3 catalysts supported on aluminosilicate halloysite nanotubes
  52. Corylus avellana leaf extract-mediated green synthesis of antifungal silver nanoparticles using microwave irradiation and assessment of their properties
  53. Novel design and combination strategy of minocycline and OECs-loaded CeO2 nanoparticles with SF for the treatment of spinal cord injury: In vitro and in vivo evaluations
  54. Fe3+ and Ce3+ modified nano-TiO2 for degradation of exhaust gas in tunnels
  55. Analysis of enzyme activity and microbial community structure changes in the anaerobic digestion process of cattle manure at sub-mesophilic temperatures
  56. Synthesis of greener silver nanoparticle-based chitosan nanocomposites and their potential antimicrobial activity against oral pathogens
  57. Baeyer–Villiger co-oxidation of cyclohexanone with Fe–Sn–O catalysts in an O2/benzaldehyde system
  58. Increased flexibility to improve the catalytic performance of carbon-based solid acid catalysts
  59. Study on titanium dioxide nanoparticles as MALDI MS matrix for the determination of lipids in the brain
  60. Green-synthesized silver nanoparticles with aqueous extract of green algae Chaetomorpha ligustica and its anticancer potential
  61. Curcumin-removed turmeric oleoresin nano-emulsion as a novel botanical fungicide to control anthracnose (Colletotrichum gloeosporioides) in litchi
  62. Antibacterial greener silver nanoparticles synthesized using Marsilea quadrifolia extract and their eco-friendly evaluation against Zika virus vector, Aedes aegypti
  63. Optimization for simultaneous removal of NH3-N and COD from coking wastewater via a three-dimensional electrode system with coal-based electrode materials by RSM method
  64. Effect of Cu doping on the optical property of green synthesised l-cystein-capped CdSe quantum dots
  65. Anticandidal potentiality of biosynthesized and decorated nanometals with fucoidan
  66. Biosynthesis of silver nanoparticles using leaves of Mentha pulegium, their characterization, and antifungal properties
  67. A study on the coordination of cyclohexanocucurbit[6]uril with copper, zinc, and magnesium ions
  68. Ultrasound-assisted l-cysteine whole-cell bioconversion by recombinant Escherichia coli with tryptophan synthase
  69. Green synthesis of silver nanoparticles using aqueous extract of Citrus sinensis peels and evaluation of their antibacterial efficacy
  70. Preparation and characterization of sodium alginate/acrylic acid composite hydrogels conjugated to silver nanoparticles as an antibiotic delivery system
  71. Synthesis of tert-amylbenzene for side-chain alkylation of cumene catalyzed by a solid superbase
  72. Punica granatum peel extracts mediated the green synthesis of gold nanoparticles and their detailed in vivo biological activities
  73. Simulation and improvement of the separation process of synthesizing vinyl acetate by acetylene gas-phase method
  74. Review Articles
  75. Carbon dots: Discovery, structure, fluorescent properties, and applications
  76. Potential applications of biogenic selenium nanoparticles in alleviating biotic and abiotic stresses in plants: A comprehensive insight on the mechanistic approach and future perspectives
  77. Review on functionalized magnetic nanoparticles for the pretreatment of organophosphorus pesticides
  78. Extraction and modification of hemicellulose from lignocellulosic biomass: A review
  79. Topical Issue: Recent advances in deep eutectic solvents: Fundamentals and applications (Guest Editors: Santiago Aparicio and Mert Atilhan)
  80. Delignification of unbleached pulp by ternary deep eutectic solvents
  81. Removal of thiophene from model oil by polyethylene glycol via forming deep eutectic solvents
  82. Valorization of birch bark using a low transition temperature mixture composed of choline chloride and lactic acid
  83. Topical Issue: Flow chemistry and microreaction technologies for circular processes (Guest Editor: Gianvito Vilé)
  84. Stille, Heck, and Sonogashira coupling and hydrogenation catalyzed by porous-silica-gel-supported palladium in batch and flow
  85. In-flow enantioselective homogeneous organic synthesis
https://doi.org/10.1515/gps-2021-0014
Keywords for this article
8-substituted xanthines; pyrimidopetridines; 5,6-diaminouracil; green synthesis
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. MW irradiation and ionic liquids as green tools in hydrolyses and alcoholyses
  3. Effect of CaO on catalytic combustion of semi-coke
  4. Studies of Penicillium species associated with blue mold disease of grapes and management through plant essential oils as non-hazardous botanical fungicides
  5. Development of leftover rice/gelatin interpenetrating polymer network films for food packaging
  6. Potent antibacterial action of phycosynthesized selenium nanoparticles using Spirulina platensis extract
  7. Green synthesized silver and copper nanoparticles induced changes in biomass parameters, secondary metabolites production, and antioxidant activity in callus cultures of Artemisia absinthium L.
  8. Gold nanoparticles from Celastrus hindsii and HAuCl4: Green synthesis, characteristics, and their cytotoxic effects on HeLa cells
  9. Green synthesis of silver nanoparticles using Tropaeolum majus: Phytochemical screening and antibacterial studies
  10. One-step preparation of metal-free phthalocyanine with controllable crystal form
  11. In vitro and in vivo applications of Euphorbia wallichii shoot extract-mediated gold nanospheres
  12. Fabrication of green ZnO nanoparticles using walnut leaf extract to develop an antibacterial film based on polyethylene–starch–ZnO NPs
  13. Preparation of Zn-MOFs by microwave-assisted ball milling for removal of tetracycline hydrochloride and Congo red from wastewater
  14. Feasibility of fly ash as fluxing agent in mid- and low-grade phosphate rock carbothermal reduction and its reaction kinetics
  15. Three combined pretreatments for reactive gasification feedstock from wet coffee grounds waste
  16. Biosynthesis and antioxidation of nano-selenium using lemon juice as a reducing agent
  17. Combustion and gasification characteristics of low-temperature pyrolytic semi-coke prepared through atmosphere rich in CH4 and H2
  18. Microwave-assisted reactions: Efficient and versatile one-step synthesis of 8-substituted xanthines and substituted pyrimidopteridine-2,4,6,8-tetraones under controlled microwave heating
  19. New approach in process intensification based on subcritical water, as green solvent, in propolis oil in water nanoemulsion preparation
  20. Continuous sulfonation of hexadecylbenzene in a microreactor
  21. Synthesis, characterization, biological activities, and catalytic applications of alcoholic extract of saffron (Crocus sativus) flower stigma-based gold nanoparticles
  22. Foliar applications of plant-based titanium dioxide nanoparticles to improve agronomic and physiological attributes of wheat (Triticum aestivum L.) plants under salinity stress
  23. Simultaneous leaching of rare earth elements and phosphorus from a Chinese phosphate ore using H3PO4
  24. Silica extraction from bauxite reaction residue and synthesis water glass
  25. Metal–organic framework-derived nanoporous titanium dioxide–heteropoly acid composites and its application in esterification
  26. Highly Cr(vi)-tolerant Staphylococcus simulans assisting chromate evacuation from tannery effluent
  27. A green method for the preparation of phoxim based on high-boiling nitrite
  28. Silver nanoparticles elicited physiological, biochemical, and antioxidant modifications in rice plants to control Aspergillus flavus
  29. Mixed gel electrolytes: Synthesis, characterization, and gas release on PbSb electrode
  30. Supported on mesoporous silica nanospheres, molecularly imprinted polymer for selective adsorption of dichlorophen
  31. Synthesis of zeolite from fly ash and its adsorption of phosphorus in wastewater
  32. Development of a continuous PET depolymerization process as a basis for a back-to-monomer recycling method
  33. Green synthesis of ZnS nanoparticles and fabrication of ZnS–chitosan nanocomposites for the removal of Cr(vi) ion from wastewater
  34. Synthesis, surface modification, and characterization of Fe3O4@SiO2 core@shell nanostructure
  35. Antioxidant potential of bulk and nanoparticles of naringenin against cadmium-induced oxidative stress in Nile tilapia, Oreochromis niloticus
  36. Variability and improvement of optical and antimicrobial performances for CQDs/mesoporous SiO2/Ag NPs composites via in situ synthesis
  37. Green synthesis of silver nanoparticles: Characterization and its potential biomedical applications
  38. Green synthesis, characterization, and antimicrobial activity of silver nanoparticles prepared using Trigonella foenum-graecum L. leaves grown in Saudi Arabia
  39. Intensification process in thyme essential oil nanoemulsion preparation based on subcritical water as green solvent and six different emulsifiers
  40. Synthesis and biological activities of alcohol extract of black cumin seeds (Bunium persicum)-based gold nanoparticles and their catalytic applications
  41. Digera muricata (L.) Mart. mediated synthesis of antimicrobial and enzymatic inhibitory zinc oxide bionanoparticles
  42. Aqueous synthesis of Nb-modified SnO2 quantum dots for efficient photocatalytic degradation of polyethylene for in situ agricultural waste treatment
  43. Study on the effect of microwave roasting pretreatment on nickel extraction from nickel-containing residue using sulfuric acid
  44. Green nanotechnology synthesized silver nanoparticles: Characterization and testing its antibacterial activity
  45. Phyto-fabrication of selenium nanorods using extract of pomegranate rind wastes and their potentialities for inhibiting fish-borne pathogens
  46. Hydrophilic modification of PVDF membranes by in situ synthesis of nano-Ag with nano-ZrO2
  47. Paracrine study of adipose tissue-derived mesenchymal stem cells (ADMSCs) in a self-assembling nano-polypeptide hydrogel environment
  48. Study of the corrosion-inhibiting activity of the green materials of the Posidonia oceanica leaves’ ethanolic extract based on PVP in corrosive media (1 M of HCl)
  49. Callus-mediated biosynthesis of Ag and ZnO nanoparticles using aqueous callus extract of Cannabis sativa: Their cytotoxic potential and clinical potential against human pathogenic bacteria and fungi
  50. Ionic liquids as capping agents of silver nanoparticles. Part II: Antimicrobial and cytotoxic study
  51. CO2 hydrogenation to dimethyl ether over In2O3 catalysts supported on aluminosilicate halloysite nanotubes
  52. Corylus avellana leaf extract-mediated green synthesis of antifungal silver nanoparticles using microwave irradiation and assessment of their properties
  53. Novel design and combination strategy of minocycline and OECs-loaded CeO2 nanoparticles with SF for the treatment of spinal cord injury: In vitro and in vivo evaluations
  54. Fe3+ and Ce3+ modified nano-TiO2 for degradation of exhaust gas in tunnels
  55. Analysis of enzyme activity and microbial community structure changes in the anaerobic digestion process of cattle manure at sub-mesophilic temperatures
  56. Synthesis of greener silver nanoparticle-based chitosan nanocomposites and their potential antimicrobial activity against oral pathogens
  57. Baeyer–Villiger co-oxidation of cyclohexanone with Fe–Sn–O catalysts in an O2/benzaldehyde system
  58. Increased flexibility to improve the catalytic performance of carbon-based solid acid catalysts
  59. Study on titanium dioxide nanoparticles as MALDI MS matrix for the determination of lipids in the brain
  60. Green-synthesized silver nanoparticles with aqueous extract of green algae Chaetomorpha ligustica and its anticancer potential
  61. Curcumin-removed turmeric oleoresin nano-emulsion as a novel botanical fungicide to control anthracnose (Colletotrichum gloeosporioides) in litchi
  62. Antibacterial greener silver nanoparticles synthesized using Marsilea quadrifolia extract and their eco-friendly evaluation against Zika virus vector, Aedes aegypti
  63. Optimization for simultaneous removal of NH3-N and COD from coking wastewater via a three-dimensional electrode system with coal-based electrode materials by RSM method
  64. Effect of Cu doping on the optical property of green synthesised l-cystein-capped CdSe quantum dots
  65. Anticandidal potentiality of biosynthesized and decorated nanometals with fucoidan
  66. Biosynthesis of silver nanoparticles using leaves of Mentha pulegium, their characterization, and antifungal properties
  67. A study on the coordination of cyclohexanocucurbit[6]uril with copper, zinc, and magnesium ions
  68. Ultrasound-assisted l-cysteine whole-cell bioconversion by recombinant Escherichia coli with tryptophan synthase
  69. Green synthesis of silver nanoparticles using aqueous extract of Citrus sinensis peels and evaluation of their antibacterial efficacy
  70. Preparation and characterization of sodium alginate/acrylic acid composite hydrogels conjugated to silver nanoparticles as an antibiotic delivery system
  71. Synthesis of tert-amylbenzene for side-chain alkylation of cumene catalyzed by a solid superbase
  72. Punica granatum peel extracts mediated the green synthesis of gold nanoparticles and their detailed in vivo biological activities
  73. Simulation and improvement of the separation process of synthesizing vinyl acetate by acetylene gas-phase method
  74. Review Articles
  75. Carbon dots: Discovery, structure, fluorescent properties, and applications
  76. Potential applications of biogenic selenium nanoparticles in alleviating biotic and abiotic stresses in plants: A comprehensive insight on the mechanistic approach and future perspectives
  77. Review on functionalized magnetic nanoparticles for the pretreatment of organophosphorus pesticides
  78. Extraction and modification of hemicellulose from lignocellulosic biomass: A review
  79. Topical Issue: Recent advances in deep eutectic solvents: Fundamentals and applications (Guest Editors: Santiago Aparicio and Mert Atilhan)
  80. Delignification of unbleached pulp by ternary deep eutectic solvents
  81. Removal of thiophene from model oil by polyethylene glycol via forming deep eutectic solvents
  82. Valorization of birch bark using a low transition temperature mixture composed of choline chloride and lactic acid
  83. Topical Issue: Flow chemistry and microreaction technologies for circular processes (Guest Editor: Gianvito Vilé)
  84. Stille, Heck, and Sonogashira coupling and hydrogenation catalyzed by porous-silica-gel-supported palladium in batch and flow
  85. In-flow enantioselective homogeneous organic synthesis
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/gps-2021-0014/html
Scroll to top button