Skip to content
2000
image of Spirooxindole Alkaloids: Recent Progress in Synthesis using Isatin as a Versatile Building Block in Multicomponent Reactions

Abstract

Spirooxindole scaffolds are unique molecular structures with diverse biological activities. These compounds were originally extracted from plants belonging to the and families. The core structure includes an oxindole moiety that acts as both a hydrogen bond donor and acceptor, along with a cycloalkyl group fused at the C-3 position of the indole ring. The spirooxindole framework is commonly found in bioactive natural products and has emerged as a key pharmacophore in modern drug discovery. Over the past decade, researchers have explored spirooxindoles extensively due to their potential as anticancer agents and their ability to interact with various biological targets. The synthesis of these compounds has significantly expanded the chemical space of oxindoles and other heterocycles, attracting strong interest from synthetic and medicinal chemists. This review discusses recent advancements (2014–2024) in the synthesis of spirooxindoles, with a focus on the use of isatin as a key building block in Multi-Component Reactions (MCRs). Noteworthy strategies being explored include 1,3-dipolar cycloadditions and isocyanide-based Multicomponent Reactions (MCRs), alongside isatin-based MCRs, all of which leverage environmentally benign catalytic systems and cutting-edge nanocatalysts. Additionally, these investigations are incorporating advanced techniques such as microwave-assisted synthesis to streamline reaction times, photochemical processes that harness light energy, and flow chemistry for continuous synthesis.

Loading

Article metrics loading...

/content/journals/mroc/10.2174/0118756298401141250910103925
2025-10-08
2025-12-16
Loading full text...

Full text loading...

References

  1. Boddy A.J. Bull J.A. Stereoselective synthesis and applications of spirocyclic oxindoles. Org. Chem. Front. 2021 8 5 1026 1084 10.1039/D0QO01085E
    [Google Scholar]
  2. Sharma Y.B. Sravani S. Hazra A. Synthesis of spiro-oxindoles (spiroindolones) via oxidative ring contraction approach. Curr. Org. Chem. 2023 27 15 1336 1346 10.2174/0113852728253596230920115307
    [Google Scholar]
  3. Gribble G.W. Indole Ring Synthesis: From Natural Products to Drug Discovery Wiley citation 2016 10.1002/9781118695692
    [Google Scholar]
  4. Singh T.P. Singh O.M. Recent progress in biological activities of indole and indole alkaloids. Mini Rev. Med. Chem. 2017 18 1 9 25 10.2174/1389557517666170807123201 28782480
    [Google Scholar]
  5. Liu Z. Zhao F. Zhao B. Yang J. Ferrara J. Sankaran B. Venkataram Prasad B.V. Kundu B.B. Phillips G.N. Gao Y. Hu L. Zhu T. Gao X. Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins. Nat. Commun. 2021 12 1 4158 10.1038/s41467‑021‑24421‑0 34230497
    [Google Scholar]
  6. Nafie M.S. Al-Majid A.M. Ali M. Alayyaf A.A. Haukka M. Ashraf S. Ul-Haq Z. El-Faham A. Barakat A. Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells. Front Chem. 2024 12 1364378 10.3389/fchem.2024.1364378 38487783
    [Google Scholar]
  7. Yu B. Yu D.Q. Liu H.M. Spirooxindoles: Promising scaffolds for anticancer agents. Eur. J. Med. Chem. 2015 97 673 698 10.1016/j.ejmech.2014.06.056 24994707
    [Google Scholar]
  8. Khetmalis Y.M. Shivani M. Murugesan S. Chandra Sekhar K.V.G. Oxindole and its derivatives: A review on recent progress in biological activities. Biomed. Pharmacother. 2021 141 111842 10.1016/j.biopha.2021.111842 34174506
    [Google Scholar]
  9. Nasri S. Bayat M. Mirzaei F. Recent strategies in the synthesis of spiroindole and spirooxindole scaffolds. Top. Curr. Chem. 2021 379 4 25 10.1007/s41061‑021‑00337‑7 34002298
    [Google Scholar]
  10. Borah B. Raju Chowhan L. Recent updates on the stereoselective synthesis of structurally functionalized spiro-oxindoles mediated by isatin N, N´ cyclic azomethine imine 1, 3-dipoles. Tetrahedron Lett. 2022 104 154014 10.1016/j.tetlet.2022.154014
    [Google Scholar]
  11. Mei G.J. Shi F. Catalytic asymmetric synthesis of spirooxindoles: recent developments. Chem. Commun. 2018 54 50 6607 6621 10.1039/C8CC02364F 29770377
    [Google Scholar]
  12. Panda S.S. Girgis S.A. Aziz N.M. Bekheit S.M. Spirooxindole: A versatile biologically active heterocyclic scaffold. Molecules 2023 28 2 618 10.3390/molecules28020618
    [Google Scholar]
  13. Dong H. Song S. Li J. Xu C. Zhang H. Ouyang L. The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation. Bioorg. Med. Chem. Lett. 2015 25 17 3585 3591 10.1016/j.bmcl.2015.06.076 26159483
    [Google Scholar]
  14. Ye N. Chen H. Wold E.A. Shi P.Y. Zhou J. Therapeutic potential of spirooxindoles as antiviral agents. ACS Infect. Dis. 2016 2 6 382 392 10.1021/acsinfecdis.6b00041 27627626
    [Google Scholar]
  15. Islam M.S. Ghawas H.M. El-Senduny F.F. Al-Majid A.M. Elshaier Y.A.M.M. Badria F.A. Barakat A. Synthesis of new thiazolo-pyrrolidine–(spirooxindole) tethered to 3-acylindole as anticancer agents. Bioorg. Chem. 2019 82 423 430 10.1016/j.bioorg.2018.10.036 30508794
    [Google Scholar]
  16. Bora D. Kaushal A. Shankaraiah N. Anticancer potential of spirocompounds in medicinal chemistry: A pentennial expedition. Eur. J. Med. Chem. 2021 215 113263 10.1016/j.ejmech.2021.113263 33601313
    [Google Scholar]
  17. Sharma S. Monga Y. Gupta A. Singh S. 2-Oxindole and related heterocycles: Synthetic methodologies for their natural products and related derivatives. RSC Advances 2023 13 21 14249 14267 10.1039/D3RA02217J 37179999
    [Google Scholar]
  18. Ribeiro C.J.A. Amaral J.D. Rodrigues C.M.P. Moreira R. Santos M.M.M. Synthesis and evaluation of spiroisoxazoline oxindoles as anticancer agents. Bioorg. Med. Chem. 2014 22 1 577 584 10.1016/j.bmc.2013.10.048 24268795
    [Google Scholar]
  19. Sathish M. Sakla A.P. Nachtigall F.M. Santos L.S. Shankaraiah N. TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline. RSC Advances 2021 11 27 16537 16546 10.1039/D1RA02381K 35479130
    [Google Scholar]
  20. Gupta A.K. Bharadwaj M. Kumar A. Mehrotra R. Spiro-oxindoles as a promising class of small molecule inhibitors of p53–MDM2 interaction useful in targeted cancer therapy. Top. Curr. Chem. 2017 375 1 3 10.1007/s41061‑016‑0089‑0 27943171
    [Google Scholar]
  21. Singh G.S. Desta Z.Y. Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chem. Rev. 2012 112 11 6104 6155 10.1021/cr300135y 22950860
    [Google Scholar]
  22. Asif M. Azaz T. Tiwari B. Nasibullah M. Propagative isatin in organic synthesis of spirooxindoles through catalysis. Tetrahedron 2023 134 133308 10.1016/j.tet.2023.133308
    [Google Scholar]
  23. Stucchi M. Lesma G. Meneghetti F. Rainoldi G. Sacchetti A. Silvani A. Organocatalytic asymmetric biginelli-like reaction involving isatin. J. Org. Chem. 2016 81 5 1877 1884 10.1021/acs.joc.5b02680 26836474
    [Google Scholar]
  24. Sharma A. Banerjee B. Multicomponent synthesis of isatin-based bioactive heterocycles. Adv. Heterocycl. Chem. 2024 142 1 70 10.1016/bs.aihch.2023.09.002
    [Google Scholar]
  25. Varun V. Sonam S. Kakkar R. Isatin and its derivatives: A survey of recent syntheses, reactions, and applications. MedChemComm 2019 10 3 351 368 10.1039/C8MD00585K 30996856
    [Google Scholar]
  26. Redkin R. Syumka E.I. Shemchuk L.A. Chernykh V.P. Synthesis and antimicrobial activity of Bis-Derivatives of 3a′ 6a′Dihydro-2'H-Spiro[Indole-3,1'-Pyrrolo[3,4-c]Pyrrole]- 2,4',6'(1H, 3'H, 5'H)-Trione. 2017 7 6 069 078 10.7324/JAPS.2017.70610
    [Google Scholar]
  27. Mondal A. A brief review depending on the chemistry of isatin in single pot technique towards the construction of significant and valuable heterocyclic scaffolds. Lett. Org. Chem. 2024 21 11 929 957 10.2174/0115701786292045240226050222
    [Google Scholar]
  28. Faisca Phillips A.M.M.M., Ed.; Synthetic Approaches to Nonaromatic Nitrogen Heterocycles. 2020 10.1002/9781119708841
    [Google Scholar]
  29. Potuganti G.R. Indukuri D.R. Nanubolu J.B. Alla M. Copper-catalyzed domino addition, hydroamination, and cyclization: A multicomponent approach to spiro oxazolidinone derivatives. J. Org. Chem. 2018 83 24 15186 15194 10.1021/acs.joc.8b02461 30465431
    [Google Scholar]
  30. Liu D. Xu H.C. Electrochemical rearrangement of indoles to spirooxindoles in continuous flow. Eur. J. Org. Chem. 2023 26 1 e202200987 10.1002/ejoc.202200987
    [Google Scholar]
  31. Huang J.R. Sohail M. Taniguchi T. Monde K. Tanaka F. Formal (4+1) cycloaddition and enantioselective michael–henry cascade reactions to synthesize spiro[4,5]decanes and spirooxindole polycycles. Angew. Chem. Int. Ed. 2017 56 21 5853 5857 10.1002/anie.201701049 28397989
    [Google Scholar]
  32. Brandão P. Marques C.S. Carreiro E.P. Pineiro M. Burke A.J. Engaging isatins in multicomponent reactions (mcrs) – easy access to structural diversity. Chem. Rec. 2021 21 4 924 1037 10.1002/tcr.202000167 33599390
    [Google Scholar]
  33. Zhou F. Liu Y.L. Zhou J. Catalytic asymmetric synthesis of oxindoles bearing a tetrasubstituted stereocenter at the c‐3 position. Adv. Synth. Catal. 2010 352 9 1381 1407 10.1002/adsc.201000161
    [Google Scholar]
  34. Tiwari G. Khanna A. Mishra V.K. Sagar R. Recent developments on microwave-assisted organic synthesis of nitrogen- and oxygen-containing preferred heterocyclic scaffolds. RSC Advances 2023 13 47 32858 32892 10.1039/D3RA05986C 37942237
    [Google Scholar]
  35. Jangale A.D. Dalal D.S. Green synthetic approaches for biologically relevant organic compounds. Synth. Commun. 2017 47 23 2139 2173 10.1080/00397911.2017.1369544
    [Google Scholar]
  36. Allais C. Grassot J.M. Rodriguez J. Constantieux T. Metal-free multicomponent syntheses of pyridines. Chem. Rev. 2014 114 21 10829 10868 10.1021/cr500099b 25302420
    [Google Scholar]
  37. Dömling A. Wang W. Wang K. Chemistry and biology of multicomponent reactions. Chem. Rev. 2012 112 6 3083 3135 10.1021/cr100233r 22435608
    [Google Scholar]
  38. Herrera R.P. Marqués-López E., Eds. Multicomponent Reactions: Concepts and Applications for Design and Synthesis 2015 10.1002/9781118863992
    [Google Scholar]
  39. Javahershenas R. Makarem A. Klika K.D. Recent advances in microwave-assisted multicomponent synthesis of spiro heterocycles. RSC Advances 2024 14 8 5547 5565 10.1039/D4RA00056K 38357035
    [Google Scholar]
  40. Zhang M. Yang W. Li K. Sun K. Ding J. Yang L. Zhu C. Facile synthesis of dispiroheterocycles through one-pot [3+2] cycloaddition, and their antiviral activity. Synthesis 2019 51 20 3847 3858 10.1055/s‑0037‑1611900
    [Google Scholar]
  41. Shanmugam P. Viswambharan B. Madhavan S. Synthesis of novel functionalized 3-spiropyrrolizidine and 3-spiropyrrolidine oxindoles from Baylis-Hillman adducts of isatin and heteroaldehydes with azomethine ylides via [3+2]-cycloaddition. Org. Lett. 2007 9 21 4095 4098 10.1021/ol701533d 17877359
    [Google Scholar]
  42. Saravanan P. Pushparaj S. Raghunathan R. An expedient approach for the synthesis of naphthyl dispiro pyrrolidine/pyrrolizidine through 1,3-dipolar cycloaddition reaction. Tetrahedron Lett. 2013 54 26 3449 3452 10.1016/j.tetlet.2013.04.091
    [Google Scholar]
  43. Parthasarathy K. Praveen C. Balachandran C. Senthil kumar, P.; Ignacimuthu, S.; Perumal, P.T. Cu(OTf)2 catalyzed three component reaction: Efficient synthesis of spiro[indoline-3,4′-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines. Bioorg. Med. Chem. Lett. 2013 23 9 2708 2713 10.1016/j.bmcl.2013.02.086 23522833
    [Google Scholar]
  44. Brita John C. Subba Reddy Y. Ravi Chandra M. Selvarajan S. Kaviyarasu K. Kulandai Therese S. Studies on the synthesis of compounds with high pharmacological activity using acenaphthoquinone. Results Chem. 2024 7 101530 10.1016/j.rechem.2024.101530
    [Google Scholar]
  45. Deng J. Mo L.P. Zhao F.Y. Zhang Z.H. Liu S.X. One-pot, three-component synthesis of a library of spirooxindole-pyrimidines catalyzed by magnetic nanoparticle supported dodecyl benzenesulfonic acid in aqueous media. ACS Comb. Sci. 2012 14 5 335 341 10.1021/co3000264 22533528
    [Google Scholar]
  46. Hu Y. Ye L. Chen J. Zhang H. Deng H. Lin J.H. Cao W. An efficient construction of CF3‐substituted spirooxindole‐fused benzo[a]quinolizidines by a three‐component cyclization. Eur. J. Org. Chem. 2021 2021 30 4405 4408 10.1002/ejoc.202100809
    [Google Scholar]
  47. Li J. Wang J. Xu Z. Zhu S. Combinatorial synthesis of functionalized spirooxindole-pyrrolidine/pyrrolizidine/pyrrolothiazole derivatives via three-component 1,3-dipolar cycloaddition reactions. ACS Comb. Sci. 2014 16 9 506 512 10.1021/co500085t 25033950
    [Google Scholar]
  48. Satasia S.P. Kalaria P.N. Avalani J.R. Raval D.K. An efficient approach for the synthesis of spirooxindole derivatives catalyzed by novel sulfated choline based heteropolyanion at room temperature. Tetrahedron 2014 70 35 5763 5767 10.1016/j.tet.2014.06.050
    [Google Scholar]
  49. Arun Y. Saranraj K. Balachandran C. Perumal P.T. Novel spirooxindole–pyrrolidine compounds: Synthesis, anticancer and molecular docking studies. Eur. J. Med. Chem. 2014 74 50 64 10.1016/j.ejmech.2013.12.027 24445312
    [Google Scholar]
  50. Han C. Meng W. Liu H. Liu Y. Tao J. DMAP-catalyzed four-component one-pot synthesis of highly functionalized spirooxindole-1,4-dihydropyridines derivatives in aqueous ethanol. Tetrahedron 2014 70 45 8768 8774 10.1016/j.tet.2014.08.048
    [Google Scholar]
  51. Alizadeh A. Moafi L. An efficient synthesis of spiro‐oxindole derivatives by three‐component reactions in water. Helv. Chim. Acta 2015 98 4 546 551 10.1002/hlca.201400263
    [Google Scholar]
  52. Poomathi N. Mayakrishnan S. Muralidharan D. Srinivasan R. Perumal P.T. Reaction of isatins with 6-amino uracils and isoxazoles: isatin ring-opening vs. annulations and regioselective synthesis of isoxazole fused quinoline scaffolds in water. Green Chem. 2015 17 6 3362 3372 10.1039/C5GC00006H
    [Google Scholar]
  53. Nayak S. Mishra K. Green synthesis of spirooxindole-pyrrolidine/piperidine fused nitrochromane: One pot three component stereo and regioselective cycloaddition. Lett. Org. Chem. 2015 13 1 11 21 10.2174/1570178612666151030213735
    [Google Scholar]
  54. Tailor Y.K. Khandelwal S. Kumari Y. Awasthi K. Kumar M. An efficient one pot three-component nanocatalyzed synthesis of spiroheterocycles using TiO2 nanoparticles as a heterogeneous catalyst. RSC Advances 2015 5 57 46415 46422 10.1039/C5RA04863J
    [Google Scholar]
  55. Brahmachari G. Banerjee B. Facile and chemically sustainable one‐pot synthesis of a wide array of fused O ‐ and N ‐heterocycles catalyzed by trisodium citrate dihydrate under ambient conditions. Asian J. Org. Chem. 2016 5 2 271 286 10.1002/ajoc.201500465
    [Google Scholar]
  56. Dalal K.S. Tayade Y.A. Wagh Y.B. Trivedi D.R. Dalal D.S. Chaudhari B.L. Chaudharia B.L. Bovine serum albumin catalyzed one-pot, three-component synthesis of dihydropyrano[2,3-c]pyrazole derivatives in aqueous ethanol. RSC Advances 2016 6 18 14868 14879 10.1039/C5RA13014J
    [Google Scholar]
  57. Shi R.G. Yan C.G. Three-component reaction for synthesis of functionalized spiro[indoline-3,4′-pyrano[3,2-h]quinolines]. Chin. Chem. Lett. 2016 27 4 575 578 10.1016/j.cclet.2016.02.016
    [Google Scholar]
  58. Tang Z. Liu Z. An Y. Jiang R. Zhang X. Li C. Jia X. Li J. Isocyanide-based multicomponent bicyclization with substituted allenoate and isatin: Synthesis of unusual spirooxindole containing [5.5]-fused heterocycle. J. Org. Chem. 2016 81 19 9158 9166 10.1021/acs.joc.6b01711 27653940
    [Google Scholar]
  59. Khanna G. Aggarwal K. Khurana J.M. Efficient catalyst-free synthesis of diversified bis (spirooxindoles) via one-pot, three-component reaction. Synth. Commun. 2016 46 23 1880 1886 10.1080/00397911.2016.1233437
    [Google Scholar]
  60. Zhang Mo. Fu, Qiu-Yang.; Gao, Ge.; He, He-Ye.; Zhang, Ying.; Wu, Yin-Su.; Zhang, Zhan-Hui. Catalyst-free, visible-light promoted one-pot synthesis of spirooxindole-pyran derivatives in aqueous ethyl lactate. ACS Sustain. Chem. Eng. 2017 5 7 6175 6182 10.1021/acssuschemeng.7b01102
    [Google Scholar]
  61. Zhang M. Liu Y.H. Shang Z.R. Hu H.C. Zhang Z.H. Supported molybdenum on graphene oxide/Fe3O4: An efficient, magnetically separable catalyst for one-pot construction of spiro-oxindole dihydropyridines in deep eutectic solvent under microwave irradiation. Catal. Commun. 2017 88 39 44 10.1016/j.catcom.2016.09.028
    [Google Scholar]
  62. Hassaneen H. Eid E. Eid H. Farghaly T. Mabkhot Y. Facial regioselective synthesis of novel bioactive spiropyrrolidine/pyrrolizine-oxindole derivatives via a three components reaction as potential antimicrobial agents. Molecules 2017 22 3 357 10.3390/molecules22030357 28245641
    [Google Scholar]
  63. Filatov A.S. Knyazev N.A. Molchanov A.P. Panikorovsky T.L. Kostikov R.R. Larina A.G. Boitsov V.M. Stepakov A.V. Synthesis of functionalized 3-spiro[cyclopropa[a]pyrrolizine]- and 3-spiro[3-azabicyclo[3.1.0]hexane]oxindoles from cyclopropenes and azomethine ylides via [3 + 2]-cycloaddition. J. Org. Chem. 2017 82 2 959 975 10.1021/acs.joc.6b02505 28004934
    [Google Scholar]
  64. Moradi L. Ataei Z. Efficient and green pathway for one-pot synthesis of spirooxindoles in the presence of CuO nanoparticles. Green Chem. Lett. Rev. 2017 10 4 380 386 10.1080/17518253.2017.1390611
    [Google Scholar]
  65. Safari E. Maryamabadi A. Hasaninejad A. Highly efficient, one-pot synthesis of novel bis-spirooxindoles with skeletal diversity via sequential multi-component reaction in PEG-400 as a biodegradable solvent. RSC Advances 2017 7 63 39502 39511 10.1039/C7RA06017C
    [Google Scholar]
  66. Ziarani G.M. Mollabaghera H. Lashgaria N. Badiei A. One-pot solvent-free synthesis of pyranonaphthoquinone-fused spirooxindoles catalyzed by SBA-IL. Iran J. Chem. Chem. Eng. 2017 25 6 3295 3304 [IJCCE]. 10.24200/sci.2018.20741
    [Google Scholar]
  67. Sapnakumari M. Narayana B. Shashidhara K.S. Sarojini B.K. Multicomponent synthesis, biological evaluation and molecular docking of new spiro-oxindole derivatives. J. Taibah Univ. Sci. 2017 11 6 1008 1018 10.1016/j.jtusci.2017.04.002
    [Google Scholar]
  68. Esmaeilpour M. Javidi J. Divar M. A green one-pot three-component synthesis of spirooxindoles under conventional heating conditions or microwave irradiation by using Fe3O4@SiO2-imid-PMAn magnetic porous nanospheres as a recyclable catalyst. J. Magn. Magn. Mater. 2017 423 232 240 10.1016/j.jmmm.2016.09.020
    [Google Scholar]
  69. Sachdeva H. Sharma S. Green preparation and structure elucidation of spiro indole derivatives using grindstone technique. 2017 1 5 170 174 10.15406/mojboc.2017.01.00031
  70. Kumar S.V. Rani G.U. Divyalakshmi M. Bhuvanesh N. Muthusubramanian S. Perumal S. Synthesis of benzosuberone-tethered spirooxindoles: 1-3-dipolar cycloaddition of azomethine ylides and arylidene benzosuberones. Mol. Divers. 2019 23 3 669 680 10.1007/s11030‑018‑9901‑9 30535898
    [Google Scholar]
  71. Chouha N. An efficient one-pot multicomponent synthesis of spirooxindole derivatives. J. Chem. Pharm. Res. 2018 10 3 113 117
    [Google Scholar]
  72. Zhang M. Yang W. Qian M. Zhao T. Yang L. Zhu C. Iodine-promoted three-component reaction for the synthesis of spirooxindoles. Tetrahedron 2018 74 9 955 961 10.1016/j.tet.2018.01.001
    [Google Scholar]
  73. Gong Y. Wang G.L. Wei Q.D. Chen L. Liu X.L. Tian M.Y. Yang J. Feng T.T. Zhou Y. Molecular hybridization-guided one-pot multicomponent synthesis of chromanone-fused 3,3′-pyrrolidinyl-dispirooxindoles through a 1,3-dipolar cycloaddition reaction. Synth. Commun. 2018 48 9 1016 1024 10.1080/00397911.2018.1428753
    [Google Scholar]
  74. Lotfy G. El Ashry E.S.H. Said M.M. Tamany E.S.E. Aziz Y.M.A. Al-Dhfyan A. Al-Majid A.M. Barakat A. Regio- and stereoselective synthesis of new spiro-oxindoles via 1,3-dipolar cycloaddition reaction: Anticancer and molecular docking studies. J. Photochem. Photobiol. B 2018 180 98 108 10.1016/j.jphotobiol.2018.01.026 29413708
    [Google Scholar]
  75. Filatov A.S. Wang S. Khoroshilova O.V. Lozovskiy S.V. Larina A.G. Boitsov V.M. Stepakov A.V. A stereo- and regioselective 1,3-dipolar cycloaddition of the stable ninhydrin-derived azomethine ylide to cyclopropenes. Trapping of unstable cyclopropene dipolarophiles. J. Org. Chem. 2019 84 11 7017 7036 10.1021/acs.joc.9b00753 31066276
    [Google Scholar]
  76. Balaboina R. Thirukovela N.S. Kankala S. Balasubramanian S. Bathula S.R. Vadde R. Jonnalagadda S.B. Vasam C.S. Synergistic catalysis of Ag(I) and organo‐ N‐heterocyclic carbenes: one‐pot synthesis of new anticancer spirooxindole‐1,4‐dihydropyridines. ChemistrySelect 2019 4 9 2562 2567 10.1002/slct.201803507
    [Google Scholar]
  77. Divar M. Zomorodian K. Sabet R. Moeini M. Khabnadideh S. An efficient method for synthesis of some novel spirooxindole-4H-pyran derivatives. Polycycl. Aromat. Compd. 2021 41 7 1549 1562 10.1080/10406638.2019.1686405
    [Google Scholar]
  78. Barakat A. Islam M.S. Ghawas H.M. Al-Majid A.M. El-Senduny F.F. Badria F.A. Elshaier Y.A.M.M. Ghabbour H.A. Design and synthesis of new substituted spirooxindoles as potential inhibitors of the MDM2–p53 interaction. Bioorg. Chem. 2019 86 598 608 10.1016/j.bioorg.2019.01.053 30802707
    [Google Scholar]
  79. Bhandari S. Sana S. Sridhar B. Shankaraiah N. Microwave‐Assisted One‐Pot [3+2] cycloaddition of azomethine ylides and 3‐alkenyl oxindoles: A facile approach to pyrrolidine‐fused bis‐spirooxindoles. ChemistrySelect 2019 4 5 1727 1730 10.1002/slct.201802847
    [Google Scholar]
  80. Khojasteh-Khosro S. Shahbazi-Alavi H. Preparation of spirooxindoles catalyzed by nano-Co 3 S 4 under microwave irradiations. J. Chem. Res. 2019 43 3-4 107 111 10.1177/1747519819841791
    [Google Scholar]
  81. Zhang W.H. Chen M.N. Hao Y. Jiang X. Zhou X.L. Zhang Z.H. Choline chloride and lactic acid: A natural deep eutectic solvent for one-pot rapid construction of spiro[indoline-3,4′-pyrazolo[3,4-b]pyridines]. J. Mol. Liq. 2019 278 124 129 10.1016/j.molliq.2019.01.065
    [Google Scholar]
  82. Shi T. Teng S. Wei Y. Guo X. Hu W. Synthesis of spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives via a multi-component cascade reaction of α-diazo esters, water, isatins and malononitrile/ethyl cyanoacetate. Green Chem. 2019 21 18 4936 4940 10.1039/C9GC01751H
    [Google Scholar]
  83. Arvinnezhad H. Ghorbani F. Khosravi H. Jadidi K. Notash B. Naderi S. Exo/endo stereocontrolled synthesis of spiroindoloindolizidines by using classical and microwave conditions via the 1,3‐dipolar cycloaddition reaction. J. Heterocycl. Chem. 2020 57 8 3222 3229 10.1002/jhet.4005
    [Google Scholar]
  84. Wu C. Liu J. Kui D. Lemao Y. Yingjie X. Luo X. Meiyang X. Shen R. Efficient multicomponent synthesis of spirooxindole derivatives catalyzed by copper triflate. Polycycl. Aromat. Compd. 2022 42 1 277 289 10.1080/10406638.2020.1726976
    [Google Scholar]
  85. Ghosh R. Vitor J.B. Mendes E. Paulo A. Acharya P.C. Stereoselective synthesis of spirooxindole derivatives using one-pot multicomponent cycloaddition reaction and evaluation of their antiproliferative efficacy. ACS Omega 2020 5 42 27332 27343 10.1021/acsomega.0c03675 33134696
    [Google Scholar]
  86. Devi T.J. Singh T.P. Singh O.M. The one-pot four-component eco-friendly synthesis of spirooxindoles in deep eutectic solvent. J. Chem. Sci. 2020 132 1 28 10.1007/s12039‑019‑1730‑6
    [Google Scholar]
  87. Nivetha N. Thangamani A. Dispirooxindole-pyrrolothiazoles: Synthesis, anti-cancer activity, molecular docking and green chemistry metrics evaluation. J. Mol. Struct. 2021 1242 130716 10.1016/j.molstruc.2021.130716
    [Google Scholar]
  88. de Silva N.H. Pyreddy S. Blanch E.W. Hügel H.M. Maniam S. Microwave-assisted rapid synthesis of spirooxindole-pyrrolizidine analogues and their activity as anti-amyloidogenic agents. Bioorg. Chem. 2021 114 105128 10.1016/j.bioorg.2021.105128 34225163
    [Google Scholar]
  89. Safaei-Ghomi J. Babaei P. Elyasi Z. Solvothermal Fabrication of NiO/Co3O4 spherical composites modified with n‐doped graphene quantum dots as a catalyst in the microwave‐assisted synthesis of spiro[diindenopyridine‐indoline] triones. ChemistrySelect 2021 6 32 8402 8410 10.1002/slct.202101651
    [Google Scholar]
  90. Mohammadi S. Naeimi H. A synergetic effect of sonication with yolk-shell nanocatalyst for green synthesis of spirooxindoles. Green Chem. Lett. Rev. 2021 14 2 345 357 10.1080/17518253.2021.1921284
    [Google Scholar]
  91. De Silva N.H. Dahdah A. Blanch E.W. Hügel H.M. Maniam S. Regioselective pyrrolizidine bis-spirooxindoles as efficient anti-amyloidogenic agents. Eur. J. Med. Chem. 2022 240 114566 [https://doi.org/10.1016/j.ejmech.2022.114566
    [Google Scholar]
  92. Westphal R. Venturini Filho E. Loureiro L.B. Tormena C.F. Pessoa C. Guimarães C.J. Manso M.P. Fiorot R.G. Campos V.R. Resende J.A.L.C. Medici F. Greco S.J. Green synthesis of spiro compounds with potential anticancer activity through knoevenagel/michael/cyclization multicomponent domino reactions organocatalyzed by ionic liquid and microwave-assisted. Molecules 2022 27 22 8051 10.3390/molecules27228051 36432151
    [Google Scholar]
  93. Benaglia M. Greco S.J. Westphal R. Filho V.E. Medici F. Stereoselective domino reactions in the synthesis of spiro compounds. Synthesis 2022 54 13 2927 2975 10.1055/a‑1771‑0641
    [Google Scholar]
  94. Naglaa F.H.M. Rizk S.A. Galal A.E. Ali A.K. Expeditious microwavable one-pot synthesis and biological exploration of spiro[indoline-3,4′-pyrazolo[3,4-b] pyridine derivatives. J. Indian Chem. Soc. 2022 19 8 3711 3719 10.1007/s13738‑022‑02568‑x
    [Google Scholar]
  95. Sharma R. Yadav L. Nasim A.A. Yadav R.K. Chen R.H. Kumari N. Ruiqi F. Sharon A. Sahu N.K. Ippagunta S.K. Coghi P. Wong V.K.W. Chaudhary S. Chemo-/Regio-selective synthesis of novel functionalized spiro[pyrrolidine-2,3′-oxindoles] under microwave irradiation and their anticancer activity. Molecules 2023 28 18 6503 10.3390/molecules28186503 37764279
    [Google Scholar]
  96. Shi Y. Zhao H. Zhao Y. An efficient synthesis of oxygen-bridged spirooxindoles via microwave-promoted multicomponent reaction. Molecules 2023 28 8 3508 10.3390/molecules28083508 37110742
    [Google Scholar]
  97. Raheja B.K. Dalal D.S. Ammonium acetate mediated simple, rapid, and one-pot multicomponent synthesis of spirooxindole derivatives. Synth. Commun. 2023 53 11 808 822 10.1080/00397911.2023.2199357
    [Google Scholar]
  98. Zhang M. Shi L. Chen L. Liu Z. Zhao T. Zhu C. Yang L. A water mediated multicomponent reaction for the synthesis of novel spirooxindole derivatives and their antifungal activity. Org. Biomol. Chem. 2024 22 17 3459 3467 10.1039/D4OB00256C 38597668
    [Google Scholar]
  99. Mondal N. Singh D. Kumari V. Choudhury L.H. Visible light‐mediated multicomponent synthesis of spirooxindole‐linked fused pyrans: An eco‐friendly one‐pot strategy. ChemistrySelect 2024 9 37 e202402549 10.1002/slct.202402549
    [Google Scholar]
  100. Rávai B. Németh Á.S. Kelemen Z. Bálint E. Microwave‐assisted multicomponent synthesis of spirooxindole dihydropyridine bisphosphonates. Eur. J. Org. Chem. 2025 28 6 e202400873 10.1002/ejoc.202400873
    [Google Scholar]
/content/journals/mroc/10.2174/0118756298401141250910103925
Loading
/content/journals/mroc/10.2174/0118756298401141250910103925
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: multicomponent ; alkaloid ; indole ; isatin ; stereoselective ; Spiro
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test