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Mini-Reviews in Organic Chemistry

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ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

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Review Article

Developments in Synthesis Strategies of Spiro-Barbiturate Compounds: A Classified Study

Author(s): Devanshi Magoo*, Anju Srivastava*, Shruti Gupta, Reena Jain, Soma Mondal Ghorai, Yashna Dawer, Sumedha Sengupta and Soni Rani

Volume 21, Issue 2, 2024

Published on: 22 June, 2023

Page: [246 - 270] Pages: 25

DOI: 10.2174/1570193X20666230428112212

Price: $65

Abstract

Spiro compounds being multi-cyclic systems linked by a single atom, have distinct three dimensionalities, and prominently hold a position of interest in the fields of synthetic and medicinal chemistry, pharmacology, material sciences and physics. Spirobarbiturate compounds which incorporate barbituric ring derivatives into spirocyclic structures have emerged as attractive synthetic targets for drug discovery as they are known to exhibit far-ranging pharmacological applications. In this review, we aim to bring to light the extensive, contemporary research applied to the synthesis of different spirobarbiturates having varied ring sizes (3, 5, 6 and 7 membered) in a classified manner. It presents the reported methods of synthesis along with their mechanistic pathways as well as the pharmacological activities of some of these synthesized biologically significant motifs.

Keywords: Spirobarbiturates, multi-component reactions, green synthesis, pharmacological applications, one-pot domino reactions, GABA receptors.

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[1]
Galati, E.M.; Monforte, M.T.; Miceli, N.; Raneri, E. Anticonvulsant and sedative effects of some 5-substituted bromopyrazolinic spirobarbiturates. Farmaco, 2001, 56(5-7), 459-461.
[http://dx.doi.org/10.1016/S0014-827X(01)01062-X] [PMID: 11482778]
[2]
a) King, S.B.; Stratford, E.S.; Craig, C.R.; Fifer, E.K. Synthesis and pharmacological evaluation of spiro-analogues of 5-benzyl-5-ethyl barbituric acid. Pharm. Res., 1995, 12(8), 1240-1243.
[http://dx.doi.org/10.1023/A:1016236615559] [PMID: 7494841];
b) Zimmerman, H.E.; Cutshall, T.W. The stereochemistry of ketonization. VI. Decarboxylation of 2-phenylcyclohexane-1,1-dicarboxylic acid. J. Am. Chem. Soc., 1958, 80(11), 2893-2896.
[http://dx.doi.org/10.1021/ja01544a074];
c) Hathaway, B.A.; Nichols, D.E.; Nichols, M.B.; Yim, G.K.W. A new, potent, conformationally-restricted analog of amphetamine: 2-amino-1,2-dihydronaphthalene. J. Med. Chem., 1982, 25(5), 535-538.
[http://dx.doi.org/10.1021/jm00347a011] [PMID: 6123601]
[3]
Lee, W.C. Comparative depression of several short acting barbiturates and spiro-barbiturates. Jpn. J. Pharmacol., 1952, 2(2), 123-126.
[http://dx.doi.org/10.1254/jjp.2.123] [PMID: 13084308]
[4]
Barakat, A.; Islam, M.S.; Al-Majid, A.M.; Ghabbour, H.A.; Fun, H.K.; Javed, K.; Imad, R.; Yousuf, S.; Choudhary, M.I.; Wadood, A. Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives. Bioorg. Med. Chem., 2015, 23(20), 6740-6748.
[http://dx.doi.org/10.1016/j.bmc.2015.09.001] [PMID: 26381063]
[5]
Fraser, W.; Suckling, C.J.; Wood, H.C.S. Latent inhibitors. Part 7. Inhibition of dihydro-orotate dehydrogenase by spirocyclopropanobarbiturates. J. Chem. Soc., Perkin Trans. 1, 1990, 1(11), 3137-3144.
[http://dx.doi.org/10.1039/p19900003137]
[6]
Kim, S.H.; Pudzianowski, A.T.; Leavitt, K.J.; Barbosa, J.; McDonnell, P.A.; Metzler, W.J.; Rankin, B.M.; Liu, R.; Vaccaro, W.; Pitts, W. Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg. Med. Chem. Lett., 2005, 15(4), 1101-1106.
[http://dx.doi.org/10.1016/j.bmcl.2004.12.016] [PMID: 15686921]
[7]
Bagherinejad, A.; Alizadeh, A. A review of the synthetic strategies toward spirobarbiturate-fused 3- to 7-membered rings. Org. Biomol. Chem., 2022, 20(36), 7188-7215.
[http://dx.doi.org/10.1039/D2OB01326F] [PMID: 36070341]
[8]
Dorofeeva, E.O.; Elinson, M.N.; Vereshchagin, A.N.; Stepanov, N.O.; Bushmarinov, I.S.; Belyakov, P.A.; Sokolova, O.O.; Nikishin, G.I. Electrocatalysis in MIRC reaction strategy: Facile stereoselective approach to medicinally relevant spirocyclopropylbarbiturates from barbituric acids and activated olefins. RSC Advances, 2012, 2(10), 4444-4452.
[http://dx.doi.org/10.1039/c2ra20078c]
[9]
Wang, X.; Lee, Y.R. Efficient synthesis of spirobarbiturates and spirothiobarbiturates bearing cyclopropane rings by Rhodium(II)-catalyzed reactions of cyclic diazo compounds. Bull. Korean Chem. Soc., 2013, 34(6), 1735-1740.
[http://dx.doi.org/10.5012/bkcs.2013.34.6.1735]
[10]
Mukherjee, P.; Das, A.R. Spirocyclopropanes from intramolecular cyclopropanation of pyranopyrazoles and pyranopyrimidine-diones and lewis acid mediated (3 + 2) cycloadditions of spirocyclopropylpyrazolones. J. Org. Chem., 2017, 82(5), 2794-2802.
[http://dx.doi.org/10.1021/acs.joc.7b00089] [PMID: 28182406]
[11]
Song, X.; Chang, J.; Zhu, Y.; Zhao, S.; Zhang, M. Diastereoselective synthesis of spirobarbiturate-cyclopropanes through organobase-mediated spirocyclopropanation of barbiturate-based olefins with benzyl chloride. Synthesis, 2019, 51(4), 899-906.
[http://dx.doi.org/10.1055/s-0037-1609637]
[12]
Yan, X.; Shao, P.; Song, X.; Zhang, C.; Lu, C.; Liu, S.; Li, Y. Chemoselective syntheses of spirodihydrofuryl and spirocyclopropyl barbiturates via cascade reactions of barbiturate-based olefins and acetylacetone. Org. Biomol. Chem., 2019, 17(10), 2684-2690.
[http://dx.doi.org/10.1039/C9OB00004F] [PMID: 30768085]
[13]
Chande, M.S.; Sudgare, V.V. Novel synthesis of fused ring [l,4]benzothiazines/[1,4]benzoxazines and related heterocycles. Indian J. Chem., 2000, 39B, 65-67.
[14]
Singh, P.; Paul, K. A practical approach for spiro- and 5-monoalkylated barbituric acids. J. Chem., 2009, 43, 607-612.
[15]
Kotha, S.; Deb, A.C. Design and synthesis of spiro-heterocycles by ring-closing metathesis. Indian J. Chem., 2008, 47B, 1120-1134.
[16]
Liu, Y.; Yang, W.; Wu, Y.; Mao, B.; Gao, X.; Liu, H.; Sun, Z.; Xiao, Y.; Guo, H. Asymmetric construction of highly functionalized spirobarbiturate-cyclopentenes through chiral phosphine-catalyzed [3+2] annulation of morita-baylis-hillman carbonates with barbiturate-derived alkenes. Adv. Synth. Catal., 2016, 358(18), 2867-2872.
[http://dx.doi.org/10.1002/adsc.201600450]
[17]
Lomlim, L.; Einsiedel, J.; Heinemann, F.W.; Meyer, K.; Gmeiner, P. Proline derived spirobarbiturates as highly effective β-turn mimetics incorporating polar and functionalizable constraint elements. J. Org. Chem., 2008, 73(9), 3608-3611.
[http://dx.doi.org/10.1021/jo702573z] [PMID: 18363364]
[18]
Krasnov, K.A.; Khrustalev, V.N. Diastereoselective T-Reaction of 1-Alkyl-5-(5-nitro-2- N -morpholino-benzylidene)barbituric acids in the solid state: Synthesis of 1-Alkyl-2,4,6-trioxoperhydro-pyrimidino-5- spiro -10′-(7′-nitro-1′3′4′9′10′10a′-hexahydro-2′-oxa)-4a′-azaphenanthrenes and their 2′-thia analogues. Cryst. Growth Des., 2014, 14(8), 3975-3982.
[http://dx.doi.org/10.1021/cg500570u]
[19]
Girgis, A.S.; Farag, H.; Ismail, N.S.M.; George, R.F. Synthesis, hypnotic properties and molecular modeling studies of 1,2,7,9-tetraaza-spiro[4.5]dec-2-ene-6,8,10-triones. Eur. J. Med. Chem., 2011, 46(10), 4964-4969.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.058] [PMID: 21872366]
[20]
Teimouri, M.B.; Akbari-Moghaddam, P.; Motaghinezhad, M. Urotropine–bromine promoted synthesis of functionalized oxaspirotricyclic furopyrimidines via a domino Knoevenagel condensation/Michael addition/α-bromination/Williamson cycloetherification sequence in water. Tetrahedron, 2013, 69(33), 6804-6809.
[http://dx.doi.org/10.1016/j.tet.2013.06.030]
[21]
Kotha, S.; Ali, R. Diversity oriented approach to spirobarbituric acid derivatives via a [2+2+2] Cycloaddition and diels‒alder reaction as key steps. Heterocycles, 2014, 88(1), 789-797.
[http://dx.doi.org/10.3987/COM-13-S(S)48]
[22]
a) Soleimani, E.; Yazdani, H.; Saei, P. Synthesis of spiro 3-bromo-4,5-dihydroisoxazoles via [1,3]dipolar cycloaddition reactions. Tetrahedron Lett., 2015, 56(13), 1635-1637.
[http://dx.doi.org/10.1016/j.tetlet.2015.02.006];
b) Rohloff, J.C.; Robinson, J., III; Gardner, J.O. Bromonitrile oxide [3+2] cycloadditions in water. Tetrahedron Lett., 1992, 33(22), 3113-3116.
[http://dx.doi.org/10.1016/S0040-4039(00)79827-3]
[23]
Hosseini, Y.; Rastgar, S.; Heren, Z.; Büyükgüngörc, O.; Pesyan, N.N. One-pot new barbituric acid derivatives derived from the reaction of barbituric acids with brcn and ketones. J. Chin. Chem. Soc., 2011, 58(3), 309-318.
[http://dx.doi.org/10.1002/jccs.201190031]
[24]
a) Kato, S.; Poling, M.; Van der Helm, D.; Dryhurst, G. Electrochemical synthesis and structure of a new cyclic barbiturate. J. Am. Chem. Soc., 1974, 96(16), 5255-5257.
[http://dx.doi.org/10.1021/ja00823a043] [PMID: 4851811];
b) Kato, S.; Dryhurst, G. Electrochemical oxidation of barbituric acids at low pH in the presence of chloride ion. J. Electroanal. Chem. Interfacial Electrochem., 1975, 62(2), 415-431.
[http://dx.doi.org/10.1016/0022-0728(75)80010-6];
c) Poling, M.; Van der Helm, D. 5,6-Dihydro-1,3-dimethyl-5,6-bis[1′3′-dimethyl-2′4′6′-trioxopyrimid(5,5′)yl]furo[2,3- d]uracil. Acta Crystallogr. B, 1976, 32(12), 3349-3351.
[http://dx.doi.org/10.1107/S0567740876010327]
[25]
Jalilzadeh, M. Noroozi Pesyan, N.; Rezaee, F.; Rastgar, S.; Hosseini, Y.; Şahin, E. New one-pot synthesis of spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]pentaones and their sulfur analogues. Mol. Divers., 2011, 15(3), 721-731.
[http://dx.doi.org/10.1007/s11030-011-9302-9] [PMID: 21279439]
[26]
Jalilzadeh, M.; Pesyan, N.N. One-pot four component reaction of unsymmetrical 1-methylbarbituric acid with brcn and various aldehydes in the presence of et3n and/or pyridine. J. Korean Chem. Society, 2011, 55(6), 940-951.
[http://dx.doi.org/10.5012/jkcs.2011.55.6.940]
[27]
Shahvirdi, S.; Rashidnejad, H.; Noroozi Pesyan, N. The organocatalytic role of L-(+)-tartaric acid in the synthesis of 5-aryl-1,1′- and 5-aryl-3,1′-dimethyl-1H,1′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]2,2′4,4′6′(3H,3′H,5H)-pentaones. J. Indian Chem. Soc., 2021, 18(2), 457-465.
[http://dx.doi.org/10.1007/s13738-020-02041-7]
[28]
Noroozi Pesyan, N.; Shokr, A.; Gharib, A.; Tunç, T.; Sahin, E. Regioselective one-pot synthesis of new unsymmetric spiro dihydrofurans in the reaction of mixed two different cyclic β-dicarbonyl compounds with BrCN and aldehydes in the presence of Et3N. J. Chin. Chem. Soc., 2015, 62(3), 234-242.
[http://dx.doi.org/10.1002/jccs.201400224]
[29]
Gao, X.; Li, Z.; Yang, W.; Liu, Y.; Chen, W.; Zhang, C.; Zheng, L.; Guo, H. Phosphine-catalyzed [3 + 2] and [4 + 2] annulation reactions of ynones with barbiturate-derived alkenes. Org. Biomol. Chem., 2017, 15(25), 5298-5307.
[http://dx.doi.org/10.1039/C7OB01034F] [PMID: 28598480]
[30]
Gupta, S.; Aggarwal, K.; Khurana, J.M. Synthesis of novel functionalized Triphenylphosphanylidene-Spirobarbiturates through a three-component reaction. ChemistrySelect, 2018, 3(15), 4110-4113.
[http://dx.doi.org/10.1002/slct.201800264]
[31]
Pakravan, N.; Shayani-Jam, H.; Beiginejad, H.; Tavafi, H.; Paziresh, S. A green method for the synthesis of novel spiro compounds: Enhancement of antibacterial properties of caffeic acid through electrooxidation in the presence of barbituric acid derivatives. J. Electroanal. Chem., 2019, 848, 113286.
[http://dx.doi.org/10.1016/j.jelechem.2019.113286]
[32]
Nagaraju, S.; Sathish, K.; Paplal, B.; Kashinath, D. “On-water” catalyst-free, one-pot synthesis of quaternary centered and spiro-tetrahydrothiophene-barbiturate hybrids. Tetrahedron Lett., 2017, 58(29), 2865-2871.
[http://dx.doi.org/10.1016/j.tetlet.2017.06.029]
[33]
Gopal Hegde, S.; Koodlur, L.; Narayanarao, M. Regioselective synthesis and biological evaluation of novel dispiropyrrolidine derivatives via one-pot four-component reaction. Synth. Commun., 2019, 49(24), 3453-3464.
[http://dx.doi.org/10.1080/00397911.2019.1672746]
[34]
Wang, C.C.; Zhou, J.; Ma, Z.W.; Chen, X.P.; Chen, Y.J. Synthesis of spirobarbiturate-pyrrolidinones via a domino aza-Michael/S N 2 cyclization of barbiturate-derived alkenes with N -alkoxy α-haloamides. Org. Biomol. Chem., 2019, 17(41), 9200-9208.
[http://dx.doi.org/10.1039/C9OB01992H] [PMID: 31596301]
[35]
Liu, S.; Shao, P.; Li, Y.; Wang, D.; Hou, D.; Qu, C.; Song, X.; Yan, X. Regioselective synthesis of spirobarbiturate-dihydrofurans and dihydrofuro[2,3-d]pyrimidines via one-pot cascade reaction of barbiturate-based olefins and ethyl acetoacetate. Tetrahedron, 2021, 79, 131859.
[http://dx.doi.org/10.1016/j.tet.2020.131859]
[36]
Alizadeh, A.; Bagherinejad, A.; Kayanian, J.; Vianello, R. An experimental and computational study of new spiro-barbituric acid pyrazoline scaffolds: restricted rotation vs. annular tautomerism. New J. Chem., 2022, 46(15), 7242-7252.
[http://dx.doi.org/10.1039/D1NJ06208E]
[37]
Renard, A.; Lhomme, J.; Kotera, M. Synthesis and properties of spiro nucleosides containing the barbituric acid moiety. J. Org. Chem., 2002, 67(4), 1302-1307.
[http://dx.doi.org/10.1021/jo016194y] [PMID: 11846678]
[38]
Ingle, V.N.; Gaidhane, P.K.; Dutta, S.S.; Naha, P.P.; Sengupta, M.S. Synthesis of novel galactopyranosyl‐derived spiro barbiturates. J. Carbohydr. Chem., 2006, 25(8-9), 661-671.
[http://dx.doi.org/10.1080/07328300601039328]
[39]
Gaidhane, P.K.; Gaidhane, M.K.; Kharkate, S.K. Synthesis of novel spiro barbiturates and their glycosides. Int. J. Res. Stud. Biosci., Agric. Technol., 2015, 180-192.
[40]
a) Xu, H.; Huang, R.L.; Shu, Z.; Hong, R.; Zhang, Z. Chemoselective synthesis of 5,4′-imidazolinyl spirobarbiturates via NBS-promoted cyclization of unsaturated barbiturates and amidines. Org. Biomol. Chem., 2021, 19(22), 4978-4985.
[http://dx.doi.org/10.1039/D1OB00508A] [PMID: 34008679];
b) Xu, H.; Chen, K.; Liu, H.W.; Wang, G.W. Solvent-free N -iodosuccinimide-promoted synthesis of spiroimidazolines from alkenes and amidines under ball-milling conditions. Org. Chem. Front., 2018, 5(19), 2864-2869.
[http://dx.doi.org/10.1039/C8QO00723C]
[41]
Goel, B.; Sharma, S.; Bajaj, K.; Bansal, D.; Singh, T.; Malik, N.; Lata, S.; Tyagi, C.; Panwar, H.; Agarwal, A.; Kumar, A. Synthesis and CNS depressant activities of newer Spiro-barbiturates. Indian J. Pharm. Sci., 2005, 67, 194-199.
[42]
Bhuyan, D.; Sarma, R.; Prajapati, D. Microwave-assisted efficient synthesis of spiroquinoline derivatives via a catalyst- and solvent-free aza-Diels–Alder reaction. Tetrahedron Lett., 2012, 53(47), 6460-6463.
[http://dx.doi.org/10.1016/j.tetlet.2012.09.081]
[43]
Borah, P.; Bhuyan, P.J. Synthesis of some novel spiro substituted pyrido[2,3-c]coumarins by exploring ‘tertiary amino effect’ reaction strategy. Tetrahedron Lett., 2013, 54(50), 6949-6951.
[http://dx.doi.org/10.1016/j.tetlet.2013.10.055]
[44]
Ziarani, G.M.; Asadi, S.; Faramarzi, S.; Amanlou, M. Green synthesis and urease inhibitory activity of spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives. Iran. J. Pharm. Res., 2015, 14, 1105-1114.
[45]
Pesyan, N.N. Noori, S.; Poorhassan, S.; Şahin, E. New spiro (thio) barbiturates based on cyclohexanone and bicyclo [3.1.1]heptan-6-one by nonconcerted [1+5] cycloaddition reaction and their conformational structures. Bull. Chem. Soc. Ethiop., 2014, 28, 423-440.
[http://dx.doi.org/10.4314/bcse.v28i3.12]
[46]
Aggarwal, K.; Vij, K.; Khurana, J.M. An efficient catalyst free synthesis of nitrogen containing spiro heterocycles via [5 + 1] double Michael addition reaction. RSC Advances, 2014, 4(26), 13313-13321.
[http://dx.doi.org/10.1039/c4ra00521j]
[47]
Bhaskarachar, R.K.; Revanasiddappa, V.G.; Hegde, S.; Balakrishna, J.P.; Reddy, S.Y. Design, synthesis and anticancer activity of functionalized spiro-quinolines with barbituric and thiobarbituric acids. Med. Chem. Res., 2015, 24(9), 3516-3528.
[http://dx.doi.org/10.1007/s00044-015-1408-7]
[48]
De Crescentini, L.; Attanasi, O.A.; Campisi, L.A.; Favi, G.; Lillini, S.; Ursini, F.; Mantellini, F. Double Michael addition/aza-cyclization: A valuable sequence for the construction of symmetrical and unsymmetrical spirobarbiturate-pyridines. Tetrahedron, 2015, 71(39), 7282-7292.
[http://dx.doi.org/10.1016/j.tet.2015.04.004]
[49]
Liu, H.; Liu, Y.; Yuan, C.; Wang, G.P.; Zhu, S.F.; Wu, Y.; Wang, B.; Sun, Z.; Xiao, Y.; Zhou, Q.L.; Guo, H. Enantioselective synthesis of spirobarbiturate-Cyclohexenes through phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. Org. Lett., 2016, 18(6), 1302-1305.
[http://dx.doi.org/10.1021/acs.orglett.6b00239] [PMID: 26937706]
[50]
Krasnov, K.A.; Dorovatovskii, P.V.; Zubavichus, Y.V.; Timofeeva, T.V.; Khrustalev, V.N. Hydride transfer reactions of 5-(2-alkohybenzylidene) barbituric acids: Synthesis of 2,4,6-trioxoperhydropyrimidine-5-spiro-3′-chromanes. Tetrahedron, 2017, 73(5), 542-549.
[http://dx.doi.org/10.1016/j.tet.2016.12.045]
[51]
Yu, M.; Wu, Y.; Peng, X.; Han, J.; Chen, J.; Kan, Y.; Deng, H.; Shao, M.; Zhang, H.; Cao, W. First diastereoselective synthesis of perfluoroalkylated cis-spiropyrido[2,1-a]isoquinoline-1,5′-pyrimidines. J. Fluor. Chem., 2018, 216, 33-42.
[http://dx.doi.org/10.1016/j.jfluchem.2018.09.007]
[52]
Huo, M.; Zhou, J.; Bai, L.; Xu, Q.; Zhou, Z.; Zhou, H.; Liang, G. High diastereoselective synthesis of spiro-barbituratechromans via domino oxa-Michael/1,6-addition reactions of ortho-hydroxyphenylsubstituted para-quinone methides with barbiturate-based olefins. Tetrahedron, 2019, 75(51), 130752.
[http://dx.doi.org/10.1016/j.tet.2019.130752]
[53]
Liu, X.; Wang, C.; Wang, X.; Ma, Z.; Meng, L.; Ding, D.; Liu, J.; Chen, Y. Synthesis of spirobarbiturate Piperidin-2-one derivatives via Cascade Aza-Michael/Michael cyclization reaction. Youji Huaxue, 2021, 41(11), 4450-4458.
[http://dx.doi.org/10.6023/cjoc202105045]
[54]
Kesharwani, S.; Sahu, N.K.; Kohli, D.V. Synthesis and biological evaluation of some new spiro derivatives of barbituric acid. Pharm. Chem. J., 2009, 43(6), 315-319.
[http://dx.doi.org/10.1007/s11094-009-0298-8]
[55]
Gao, X.; Zhu, D.; Chen, Y.; Deng, H.; Jiang, F.; Wang, W.; Wu, Y.; Guo, H. Palladium-Catalyzed [5 + 2] annulation of vinylethylene carbonates with barbiturate-derived alkenes. Org. Lett., 2020, 22(18), 7158-7163.
[http://dx.doi.org/10.1021/acs.orglett.0c02508] [PMID: 32883084]

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