Login Register Cart 0
Generic placeholder image

Current Organocatalysis

Editor-in-Chief

ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Mandelic Acid: An Efficient Organo-catalyst for the Synthesis of 3-substituted-3- Hydroxy-indolin-2-ones and Related Derivatives in Aqueous Ethanol at Room Temperature

Author(s): Gurpreet Kaur, Rajat Kumar, Shivam Saroch, Vivek Kumar Gupta and Bubun Banerjee*

Volume 8, Issue 1, 2021

Published on: 13 July, 2020

Page: [147 - 159] Pages: 13

DOI: 10.2174/2213337207999200713145440

Price: $65

Abstract

Background: Indoles and various indolyl derivatives are very common in naturally occurring biologically active compounds. Many methods are being developed for the synthesis of various bioactive indole derivatives.

Objective: Synthesis of biologically promising structurally diverse indole derivatives under mild and environmentally benign conditions.

Methods: Synthesis of 3-hydroxy-3-(5-(trifluoromethoxy)-1H-indol-3-yl)indolin-2-one was achieved by the reaction of an equimolar mixture of isatin and 3-(trifluoromethoxy)-1H-indol using 20 mol% of mandelic acid as catalyst in aqueous ethanol at room temperature. Under the same optimized reaction conditions, synthesis of 3-(3-hydroxy-2-oxoindolin-3-yl)chroman-2,4-diones was accomplished via the reactions of substituted isatins and 4-hydroxycoumarin. On the other hand, 2-hydroxy-2-(indol-3-yl)- indene-1,3-diones and 10-hydroxy-10-(5-methoxy-1H-indol-3- yl)phenanthren-9(10H)-one were synthesized from the reactions of indoles and ninhydrin or 9,10-phenanthrenequinone respectively using the same 20 mol% of mandelic acid as an efficient organo-catalyst in aqueous ethanol at room temperature.

Results: Mild, safe and clean reaction profiles, energy efficiency, high atom-economy, use of naturally occurring non-toxic organo-catalyst, easy isolation procedure by avoiding column chromatographic purification and gram scale production are some the major advantages of this developed protocol.

Conclusion: A simple, straightforward and eco-friendly protocol has been developed for the efficient synthesis of biologically promising novel 3-hydroxy-3-(5-(trifluoromethoxy)-1H-indol- 3-yl)indolin-2- one, 3-(3-hydroxy-2-oxoindolin-3-yl)chroman-2,4-diones, 2-hydroxy-2-(indol-3- yl)-indene-1,3-diones and 10-hydroxy-10-(5-methoxy-1H-indol-3-yl)phenanthren-9(10H)-one using a catalytic amount of mandelic acid in aqueous ethanol at room temperature.

Keywords: Indole, isatin, mandelic acid, organocatalysis, sustainable synthesis, aqueous ethanol.

« Previous Next »
Graphical Abstract

[1]
Zhang, Y-C.; Jiang, F.; Shi, F. Organocatalytic asymmetric synthesis of indole-based chiral heterocycles: strategies, reactions, and outreach. Acc. Chem. Res., 2020, 53(2), 425-446.
[http://dx.doi.org/10.1021/acs.accounts.9b00549 ] [PMID: 31820922]
[2]
Brahmachari, G.; Banerjee, B. Facile and one-pot access of 3,3-bis(indol-3-yl)indolin-2-ones and 2,2-bis(indol-3-yl)acenaphthylen-1(2H)-one derivatives via an eco-friendly pseudo-multicomponent reaction at room temperature using sulfamic acid as an organo-catalyst. ACS Sustain. Chem.& Eng., 2014, 2, 2802-2812.
[http://dx.doi.org/10.1021/sc500575h]
[3]
Vicente, R. Recent advances in indole syntheses: new routes for a classic target. Org. Biomol. Chem., 2011, 9(19), 6469-6480.
[http://dx.doi.org/10.1039/c1ob05750b ] [PMID: 21779596]
[4]
Lounasmaa, M.; Tolvanen, A. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat. Prod. Rep., 2000, 17(2), 175-191.
[http://dx.doi.org/10.1039/a809402k ] [PMID: 10821112]
[5]
Hibino, S.; Choshi, T. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat. Prod. Rep., 2001, 18(1), 66-87.
[http://dx.doi.org/10.1039/b004055j ] [PMID: 11245401]
[6]
Wu, Y.J. New indole-containing medicinal compounds. Top. Heterocycl. Chem., 2010, 26, 1-29.
[http://dx.doi.org/10.1007/7081_2010_37]
[7]
Nakamura, T.; Shirokawa, S.; Hosokawa, S.; Nakazaki, A.; Kobayashi, S. Enantioselective total synthesis of convolutamydines B and E. Org. Lett., 2006, 8(4), 677-679.
[http://dx.doi.org/10.1021/ol052871p ] [PMID: 16468740]
[8]
Tang, Y.Q.; Sattler, I.; Thiericke, R.; Grabley, S. Feng, X.Z. Maremycins C and D, New diketopiperazines, and Maremycins E and F, novel polycyclic spiro-indole metabolites isolated from Streptomyces sp. Eur. J. Org. Chem., 2001, 2001, 261-267.
[http://dx.doi.org/10.1002/1099-0690(200101)2001:2<261:AID-EJOC261>3.0.CO;2-6]
[9]
Rasmussen, H.B.; MacLeod, J.K. Total synthesis of donaxaridine. J. Nat. Prod., 1997, 60, 1152-1154.
[http://dx.doi.org/10.1021/np970246q]
[10]
Khuzhaev, V.U.; Zhalolov, I.; Turgunov, K.K.; Tashkhodzhaev, B.; Levkovich, M.G.; Aripova, S.F.; Shashkov, A.S. Alkaloids from Arundo donax. XVII. Structure of the dimeric indole alkaloid arundaphine. Chem. Nat. Compd., 2004, 40, 269-272.
[http://dx.doi.org/10.1023/B:CONC.0000039139.30391.2c]
[11]
Kagata, T.; Saito, S.; Shigemori, H.; Ohsaki, A.; Ishiyama, H.; Kubota, T.; Kobayashi, J. Paratunamides A-D, oxindole alkaloids from Cinnamodendron axillare. J. Nat. Prod., 2006, 69(10), 1517-1521.
[http://dx.doi.org/10.1021/np0602968 ] [PMID: 17067176]
[12]
Jimenez, J.I.; Huber, U.; Moore, R.E.; Patterson, G.M. Oxidized welwitindolinones from terrestrial fischerella spp. J. Nat. Prod., 1999, 62(4), 569-572.
[http://dx.doi.org/10.1021/np980485t ] [PMID: 10217710]
[13]
Suzuki, H.; Morita, H.; Shiro, M.; Kobayashi, J. Celogentin K, a new cyclic peptide from the seeds of Celosia argentea and X-ray structure of moroidin. Tetrahedron, 2004, 60, 2489-2495.
[http://dx.doi.org/10.1016/j.tet.2004.01.053]
[14]
Singh, S.B.; Jayasuriya, H.; Salituro, G.M.; Zink, D.L.; Shafiee, A.; Heimbuch, B.; Silverman, K.C.; Lingham, R.B.; Genilloud, O.; Teran, A.; Vilella, D.; Felock, P.; Hazuda, D. The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I. J. Nat. Prod., 2001, 64(7), 874-882.
[http://dx.doi.org/10.1021/np000632z ] [PMID: 11473415]
[15]
Lin, S.; Yang, Z.Q.; Kwok, B.H.B.; Koldobskiy, M.; Crews, C.M.; Danishefsky, S.J. Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR. J. Am. Chem. Soc., 2004, 126(20), 6347-6355.
[http://dx.doi.org/10.1021/ja049821k ] [PMID: 15149232]
[16]
Komakine, N.; Takaishi, Y.; Honda, G.; Ito, M.; Takeda, Y.; Kodzhimatov, O.K.; Ahurmetov, O. Indole alkaloids from Rheum maximowiczii. Nat. Med., 2005, 59, 45-48.
[17]
Takao, T.; Kitatani, F.; Watanabe, N.; Tagi, A.; Sakata, K. A simple screening method for antioxidants and isolation of several antioxidants produced by marine bacteria from fish and shellfish. Biosci. Biotechnol. Biochem., 1994, 58, 1780-1783.
[http://dx.doi.org/10.1271/bbb.58.1780]
[18]
Hewawasam, P.; Meanwell, N.A.; Gribkoff, V.K.; Dworetzky, S.I.; Boissard, C.G. Discovery of a novel class of BK channel openers: enantiospecific synthesis and bk channel opening activity of 3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trifluoromethyl)-2H-indol-2-one. Bioorg. Med. Chem. Lett., 1997, 7, 1255-1260.
[http://dx.doi.org/10.1016/S0960-894X(97)00202-3]
[19]
Tokunaga, T.; Hume, W.E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Hourai, S.; Nagamine, J.; Seki, H.; Taiji, M.; Noguchi, H.; Nagata, R. Oxindole derivatives as orally active potent growth hormone secretagogues. J. Med. Chem., 2001, 44(26), 4641-4649.
[http://dx.doi.org/10.1021/jm0103763 ] [PMID: 11741481]
[20]
Boechat, N.; Kover, W.B.; Bongertz, V.; Bastos, M.M.; Romeiro, N.C.; Azevedo, M.L.; Wollinger, W. Design, synthesis and pharmacological evaluation of HIV-1 reverse transcriptase inhibition of new indolin-2-ones. Med. Chem., 2007, 3(6), 533-542.
[http://dx.doi.org/10.2174/157340607782360326 ] [PMID: 18045202]
[21]
Sai Prathima, P.; Rajesh, P.; Venkateswara Rao, J.; Sai Kailash, U.; Sridhar, B.; Mohan Rao, M. “On water” expedient synthesis of 3- indolyl-3-hydroxy oxindole derivatives and their anticancer activity in vitro. Eur. J. Med. Chem., 2014, 84, 155-159..
[http://dx.doi.org/10.1016/j.ejmech.2014.07.004] [PMID: 25016373]
[22]
Ziarani, G.M.; Moradi, R.; Badiei, A.; Lashgari, N.; Moradi, B.; Soorki, A.A. Efficient green synthesis of 3,3-di(indolyl)indolin-2-ones using sulfonic acid functionalized nanoporous SBA-Pr-SO3H and study of their antimicrobial properties. J. Taibah Uni. Sci, 2015, 9, 555-563.
[http://dx.doi.org/10.1016/j.jtusci.2014.11.009]
[23]
Zhang, H.H.; Zhu, Z.Q.; Fan, T.; Liang, J.; Shi, F. Intermediate-dependent unusual [4+3], [3+2] and cascade reactions of 3-indolylmethanols: controllable chemodivergent and stereoselective synthesis of diverse indole derivatives. Adv. Synth. Catal., 2016, 358, 1259-1288.
[http://dx.doi.org/10.1002/adsc.201501063]
[24]
Jiang, F.; Zhang, Y.C.; Yang, X.; Zhu, Q.N.; Shi, F. Catalytic asymmetric cascade dearomatization of tryptamines with indol-3-ylmethanols: diastereo- and enantioselective synthesis of structurally complex indole derivatives. Synlett, 2016, 27, 575-580.
[25]
Tan, W.; Li, X.; Gong, Y.X.; Ge, M.D.; Shi, F. Highly diastereo- and enantioselective construction of a spiro[cyclopenta[b]indole-1,3′-oxindole] scaffold via catalytic asymmetric formal [3+2] cycloadditions. Chem. Commun. (Camb.), 2014, 50(100), 15901-15904.
[http://dx.doi.org/10.1039/C4CC07246D ] [PMID: 25380514]
[26]
Shi, F.; Zhang, H.H.; Sun, X.X.; Liang, J.; Fan, T.; Tu, S.J. Organocatalytic asymmetric cascade reactions of 7-vinylindoles: diastereo- and enantioselective synthesis of C7-functionalized indoles. Chemistry, 2015, 21(8), 3465-3471.
[http://dx.doi.org/10.1002/chem.201405245 ] [PMID: 25521722]
[27]
Shi, F.; Zhu, R.Y.; Dai, W.; Wang, C.S.; Tu, S.J. Catalytic asymmetric formal [3+3] cycloaddition of an azomethine ylide with 3-indolylmethanol: enantioselective construction of a six-membered piperidine framework. Chemistry, 2014, 20(9), 2597-2604.
[http://dx.doi.org/10.1002/chem.201304187 ] [PMID: 24488673]
[28]
Dai, W.; Lu, H.; Li, X.; Shi, F.; Tu, S.J. Diastereo- and enantioselective construction of a bispirooxindole scaffold containing a tetrahydro-β-carboline moiety through an organocatalytic asymmetric cascade reaction. Chemistry, 2014, 20(36), 11382-11389.
[http://dx.doi.org/10.1002/chem.201402485 ] [PMID: 25056997]
[29]
Hao, W.J.; Wang, J.Q.; Xu, X.P.; Zhang, S.L.; Wang, S.Y.; Ji, S.J.I. I2/O2-promoted domino reactions of isatins or 3-hydroxyindolin-2-one derivatives with enaminones. J. Org. Chem., 2013, 78(24), 12362-12373.
[http://dx.doi.org/10.1021/jo401773j ] [PMID: 24295532]
[30]
Song, J.; Guo, C.; Adele, A.; Yin, H.; Gong, L.Z. Enantioselective organocatalytic construction of hexahydropyrroloindole by means of α-alkylation of aldehydes leading to the total synthesis of (+)-gliocladin C. Chemistry, 2013, 19(10), 3319-3323.
[http://dx.doi.org/10.1002/chem.201204522 ] [PMID: 23401076]
[31]
Kinthada, L.K.; Medisetty, S.R.; Parida, A.; Babu, K.N.; Bisai, A. Kinthada, S.R.; Medisetty, A.; Parida, K.N.; Babu, A. Bisai, FeCl3- catalyzed allylation reactions onto 3-hydroxy-2-oxindoles: formal total syntheses of bis-cyclotryptamine alkaloids, (±)- Chimonanthine, and (±)-Folicanthine. J. Org. Chem., 2017, 82(16), 8548-8567..
[http://dx.doi.org/10.1021/acs.joc.7b01232] [PMID: 28718647]
[32]
Wang, S.Y.; Ji, S.J. Facile synthesis of 3,3-di(heteroaryl)indolin-2-one derivatives catalyzed by ceric ammonium nitrate (CAN) under ultrasound irradiation. Tetrahedron, 2006, 62, 1527-1535.
[http://dx.doi.org/10.1016/j.tet.2005.11.011]
[33]
Chauhan, P.; Chimni, S.S. Asymmetric addition of indoles to isatins catalysed by bifunctional modified cinchona alkaloid catalysts. Chemistry, 2010, 16(26), 7709-7713.
[http://dx.doi.org/10.1002/chem.201000846 ] [PMID: 20533467]
[34]
Shanthi, G.; Lakshmi, N.V.; Perumal, P.T. A simple and eco-friendly synthesis of 3-indolyl-3-hydroxy oxindoles and 11-indolyl-11H-indeno[1,2-b]quinoxalin-11-ols in aqueous media. ARKIVOC, 2009, 2009, 121-130.
[35]
Rad-Moghadam, K.; Sharifi-Kiasaraie, M.; Taheri-Amlashi, H. Synthesis of symmetrical and unsymmetrical 3,3-di(indolyl)indolin-2-ones under controlled catalysis of ionic liquids. Tetrahedron, 2010, 66(13), 2316-2321.
[http://dx.doi.org/10.1016/j.tet.2010.02.017 ] [PMID: 32287419]
[36]
Rad-Moghadam, K.; Gholizadeh, S. Selective and efficient synthesis of 3-indolyl-2-oxindoles under catalysis of LiClO4. Iran. J. Catal, 2014, 4, 41-47.
[37]
Kumar, V.P.; Reddy, V.P.; Sridhar, R.; Srinivas, B.; Narender, M.; Rao, K.R. Supramolecular synthesis of 3-indolyl-3-hydroxy oxindoles under neutral conditions in water. J. Org. Chem., 2008, 73(4), 1646-1648.
[http://dx.doi.org/10.1021/jo702496s ] [PMID: 18211093]
[38]
Hosseini-Sarvari, M.; Tavakolian, M. Preparation, characterization, and catalysis application of nano-rods zinc oxide in the synthesis of 3-indolyl-3-hydroxy oxindoles in water. Appl. Catal. A Gen., 2012, 441-442, 65-71.
[http://dx.doi.org/10.1016/j.apcata.2012.07.009]
[39]
Deng, J.; Zhang, S.; Ding, P.; Jiang, H.; Wang, W.; Li, J. Facile creation of 3-indolyl-3-hydroxy-2-oxindoles by an organocatalytic enantioselective Friedel-Crafts reaction of indoles with isatins. Adv. Synth. Catal., 2010, 352, 833-838.
[http://dx.doi.org/10.1002/adsc.200900851]
[40]
Vuram, P.K.; Kabilan, C.; Chadha, A. Catalyst and solvent-free microwave assisted expeditious synthesis of 3-indolyl-3-hydroxy oxindoles and unsymmetrical 3,3-di(indolyl)indolin-2-ones. Int. J. Org. Chem. (Irvine), 2015, 5, 108-118.
[http://dx.doi.org/10.4236/ijoc.2015.52012]
[41]
Hanhan, N.V.; Sahin, A.H.; Chang, T.W.; Fettinger, J.C.; Franz, A.K. Catalytic asymmetric synthesis of substituted 3-hydroxy-2-oxindoles. Angew. Chem. Int. Ed. Engl., 2010, 49(4), 744-747.
[http://dx.doi.org/10.1002/anie.200904393 ] [PMID: 20029857]
[42]
Berens, U.; Brown, J.M.; Long, J.; Seike, R. Synthesis and resolution of 2,2′-bis-diphenylphosphino [3,3′]biindolyl; A new atropisomeric ligand for transition metal catalysis. Tetrahedron Asymmetry, 1996, 7, 285-292.
[http://dx.doi.org/10.1016/0957-4166(95)00447-5]
[43]
Meshram, H.M.; Kumar, D.A.; Goud, P.R.; Reddy, B.C. Triton B-assisted, efficient, and convenient synthesis of 3-indolyl-3-hydroxy oxindoles in aqueous medium. Synth. Commun., 2010, 40, 39-45.
[http://dx.doi.org/10.1080/00397910902916072]
[44]
Nikoofar, K.; Haghighi, M.; Khademi, Z. Preparation, characterization, and catalytic application of metallic nanocrystalline MgAl2O4 in the synthesis of 3-hydroxy-3-indolyl-indolin-2-ones, symmetrical and unsymmetrical 3,3′-bis(indolyl)indolin-2-ones, and 3,3′-bis(indolyl)methanes. Arab. J. Chem., 2019, 12, 3776-3784.
[http://dx.doi.org/10.1016/j.arabjc.2016.01.013]
[45]
Rad-Moghadam, K.; Dehghan, N. Application of cellulose/chitosan grafted nano-magnetites as efficient and recyclable catalysts for selective synthesis of 3-indolylindolin-2-ones. J. Mol. Catal. Chem., 2014, 392, 97-104.
[http://dx.doi.org/10.1016/j.molcata.2014.05.005]
[46]
Liu, G.; Zhuo, M.; An, D.; Zhang, G.; Qin, X.; Gao, J.; Fan, Y.; Zhang, S. Highly enantioselective Friedel-Crafts reactions of indoles with isatins catalyzed by chiral imidodiphosphoric acids. Asian J. Org. Chem., 2017, 6, 807-811.
[http://dx.doi.org/10.1002/ajoc.201700175]
[47]
Srihari, G.; Murthy, M.M. Kaolin/KOH is an efficient heterogeneous catalyst for the synthesis of 3-hydroxy-3-indolyl oxindoles. Synth. Commun., 2011, 41, 2684-2692.
[http://dx.doi.org/10.1080/00397911.2010.515342]
[48]
Kumar, A.; Shukla, R.D.; Yadav, D.; Gupta, L.P. Friedel-Crafts alkylation of indoles in deep eutectic solvent. RSC Advances, 2015, 5, 52062-52065.
[http://dx.doi.org/10.1039/C5RA08038J]
[49]
Brahmachari, G.; Banerjee, B. Facile and one-pot access to diverse and densely functionalized 2-amino-3-cyano-4H-pyrans and pyran-annulated heterocyclic scaffolds via an eco-friendly multicomponent reaction at room temperature using urea as a novel organo-catalyst. ACS Sustain. Chem.& Eng., 2014, 2, 411-422.
[http://dx.doi.org/10.1021/sc400312n]
[50]
Banerjee, B.; Brahmachari, G. Room temperature metal-free synthesis of aryl/heteroaryl-substituted bis(6-aminouracil-5-yl)methanes using sulfamic acid (NH2SO3H) as an efficient and eco-friendly organo-catalyst. Curr. Organocatal., 2016, 3, 125-132.
[http://dx.doi.org/10.2174/2213337202666150812231130]
[51]
Brahmachari, G.; Banerjee, B. Sulfamic acid-catalyzed carbon-carbon and carbon-heteroatom bond forming reactions: An overview. Curr. Organocatal., 2016, 3, 93-124.
[http://dx.doi.org/10.2174/2213337202666150812230830]
[52]
Oliveira, V.G.; Cardoso, M.F.C.; Forezi, L.S.M. Organocatalysis: A brief overview on its evolution and applications. Catalysts, 2018, 8, 605.
[http://dx.doi.org/10.3390/catal8120605]
[53]
Banerjee, B.; Bhardwaj, V.; Kaur, A.; Kaur, G.; Singh, A. Catalytic applications of saccharin and its derivatives in organic synthesis. Curr. Org. Chem., 2019, 23, 3191-3205.
[http://dx.doi.org/10.2174/1385272823666191121144758]
[54]
Banerjee, B. Recent developments on organo-bicyclo-bases catalyzed multicomponent synthesis of biologically relevant heterocycles. Curr. Org. Chem., 2018, 22, 208-233.
[http://dx.doi.org/10.2174/1385272821666170703123129]
[55]
Kaur, G.; Bala, K.; Devi, S.; Banerjee, B. Camphorsulfonic Acid (CSA): An efficient organocatalyst for the synthesis or derivatization of heterocycles with biologically promising activities. Curr. Green Chem., 2018, 5, 150-167.
[http://dx.doi.org/10.2174/2213346105666181001113413]
[56]
Kaur, G.; Thakur, S.; Kaundal, P.; Chandel, K.; Banerjee, B. p-Dodecylbenzenesulfonic acid: An efficient Brønsted acid-surfactant-combined catalyst to carry out diverse organic transformations in aqueous medium. ChemistrySelect, 2018, 3, 12918-12936.
[http://dx.doi.org/10.1002/slct.201802824]
[57]
Kaur, G.; Singh, A.; Bala, K.; Devi, M.; Kumari, A.; Devi, S.; Devi, R.; Gupta, V.K.; Banerjee, B. Naturally occurring organic acid-catalyzed facile diastereoselective synthesis of biologically active (E)-3-(arylimino)indolin-2-one derivatives in water at room temperature. Curr. Org. Chem., 2019, 23, 1778-1788.
[http://dx.doi.org/10.2174/1385272822666190924182538]
[58]
Kaur, G.; Shamim, M.; Bhardwaj, V.; Gupta, V.K.; Banerjee, B. Mandelic acid catalyzed one-pot three-component synthesis of α-aminonitriles and α-aminophosphonates under solvent-free conditions at room temperature. Synth. Commun., 2020, 50, 1545-1560.
[http://dx.doi.org/10.1080/00397911.2020.1745844]
[59]
Singh, A.; Kaur, G.; Kaur, A.; Gupta, V.K.; Banerjee, B. A general method for the synthesis of 3,3-bis(indol-3-yl)indolin-2-ones, bis(indol-3-yl)(aryl)methanes and tris(indol-3-yl)methanes using naturally occurring mandelic acid as an efficient organo-catalyst in aqueous ethanol at room temperature. Curr. Green Chem., 2020, 7, 128-140.
[http://dx.doi.org/10.2174/2213346107666200228125715]

Rights & Permissions Print Cite
Article Metrics
17
© 2025 Bentham Science Publishers | Privacy Policy