An efficient solvent-free synthesis of 2-(alkylamino)-2-oxo-1-arylethyl-6,12-dioxo-6,12-dihydroindolo[1,2-b]isoquinoline-11-carboxylate derivatives via four-component reaction

Abstract

A one-pot approach for the synthesis of a new series of 2-(alkylamino)-2-oxo-1-arylethyl-6,12-dioxo-6,12-dihydroindolo[1,2-b]isoquinoline-11-carboxylate derivatives via a four-component reaction using isatin, homophthalic anhydride, cyclohexyl isocyanide and an aldehyde is described. This method has several advantages such as being catalyst- and solvent-free reaction and a high-efficiency process with high to excellent yields.

Graphical abstract

This is a preview of subscription content, log in to check access.

Fig. 1
Scheme 1
Scheme 2
Scheme 3

References

  1. 1.

    Goldbrunner M, Loidl G, Polossek T, Mannschreck A, von Angerer E (1997) Inhibition of tubulin polymerization by 5,6-dihydroindolo[2,1-a]isoquinoline derivatives. J Med Chem 40:3524–3533. https://doi.org/10.1021/jm970177c

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Gastpar R, Goldbrunner M, Marko D, von Angerer E (1998) Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization. J Med Chem 41:4965–4972. https://doi.org/10.1021/jm980228l

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Ambros R, Von Angerer S, Wiegrebe W (1998) C-12-Substituted indolo[2,1-a]isoquinolines as estrogen receptor affinic cytostatic agents. Arch Pharm 321:743–747. https://doi.org/10.1002/ardp.19883211010

    Article  Google Scholar 

  4. 4.

    Polossek T, Ambros R, Von Angerer S, Brandl G, Mannschreck A, Von Angerer E (1992) 6-Alkyl-12-formylindolo[2,1-a]isoquinolines. Syntheses, estrogen receptor binding affinities, and stereospecific cytostatic activity. J Med Chem 35:3537–3547. https://doi.org/10.1021/jm00097a011

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Ambros R, Schneider MR, Von Angerer S (1990) Indolo[2,1-a]isoquinolines. Syntheses, steroid hormone receptor binding affinities, and cytostatic activity. J Med Chem 33:153–160. https://doi.org/10.1021/jm00163a026

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Ambros R, Von Angerer S, Wiegrebe W (1998) Synthesis and antitumor activity of methoxy-indolo[2,1-a]isoquinolines. Arch Pharm 321:481–486. https://doi.org/10.1002/ardp.19883210811

    Article  Google Scholar 

  7. 7.

    Saundane AR, Ranganafh SH, Prayagraj G, Rudresh K, Satyanarayana ND (1998) Synthesis and pharmacological studies of some new 11H-indolo[3,2-c]isoquinolin-5-yl thio)acetyl thiosemicarbazide andits derivatives. Orient J Chem 14:251–267

    CAS  Google Scholar 

  8. 8.

    Ewing J, Hughes GK, Ritchie E, Taylor WC (1952) An alkaloid related to dehydrolaudanosoline. Nature 169:618–619. https://doi.org/10.1038/169618b0

    CAS  Article  Google Scholar 

  9. 9.

    Benington F, Morin RD (1967) Synthesis of (±)-cryptowoline iodide. J Org Chem 32:1050–1053. https://doi.org/10.1021/jo01279a040

    CAS  Article  Google Scholar 

  10. 10.

    Elliott IW Jr (1982) Synthesis of (±)-o-methylcryptaustoline iodide. J Org Chem 47:5398–5400. https://doi.org/10.1021/jo00148a035

    CAS  Article  Google Scholar 

  11. 11.

    Meyers AI, Sielecki TM (1991) Total synthesis of the dibenzopyrrocoline alkaloid S-(+)-cryptaustoline. Revision of absolute configuration due to an unusual inversion in stereochemistry. J Am Chem Soc 113:2789–2790. https://doi.org/10.1021/ja00007a084

    CAS  Article  Google Scholar 

  12. 12.

    Meyers AI, Sielecki TM, Crans DC, Marshman RW, Nguyen TH (1992) (-)-Cryptaustoline: its synthesis, revision of absolute stereochemistry, and mechanism of inversion of stereochemistry. J Am Chem Soc 114:8483–8489. https://doi.org/10.1021/ja00048a020

    CAS  Article  Google Scholar 

  13. 13.

    Cimanga K, Bruyne TD, Pieters L, Vlietinck AJ (1997) In vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinolenta. J Nat Prod 60:688–691. https://doi.org/10.1021/np9605246

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Cimanga K, De Bruyne T, Lasure A, Van Poel B, Pieters L, Claeys M, Berghe DV, Kambu K, Tona L, Vlietinck AJ (1996) In vitro biological activities of alkaloids from Cryptolepis sanguinolenta. Planta Med 62:22–27. https://doi.org/10.1055/s-2006-957789

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Noamesi BK, Bamgbose SO (1983) Studies on cryptolepine. Cryptolepine antagonism of noradrenaline and modification of this effect by calcium ions and prostaglandin E2 on rat isolated mesenteric artery. Planta Med 47:100–102. https://doi.org/10.1055/s-2007-969962

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Noamesi BK, Bamgbose SOA (1984) Studies on cryptolepine. III: effect of cryptolepine on the tone and prostaglandin production in isolated rabbit duodenum. Planta Med 50:98–101. https://doi.org/10.1055/s-2007-969633

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Noamesi BK, Bamgbose SOA (1983) Studies on cryptolepine. III: effect of cryptolepine on smooth muscle contractions and cholinergic nerve transmission of isolated guinea-pig ileum. Planta Med 48:48–51. https://doi.org/10.1055/s-2007-969877

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Van Baelen G, Meyers C, Lemière GLF, Hostyn S, Dommisse R, Maes L, Augustyns K, Haemers A, Pieters L, Maes BUW (2008) Synthesis of 6-methyl-6H-indolo[3,2-c]isoquinoline and 6-methyl-6H-indolo[2,3-c]isoquinoline: two new unnatural isoquinoline isomers of the cryptolepine series. Tetrahedron 64:11802–11809. https://doi.org/10.1016/j.tet.2008.08.116

    CAS  Article  Google Scholar 

  19. 19.

    Lötter ANC, Pathak R, Sello TS, Fernandes MA, van Otterlo WAL, de Koning CB (2007) Synthesis of the dibenzopyrrocoline alkaloid skeleton:indolo[2,1-a]isoquinolines and related analogues. Tetrahedron 63:2263–2274. https://doi.org/10.1016/j.tet.2006.12.063

    CAS  Article  Google Scholar 

  20. 20.

    Gour J, Gatadi S, Nagarsenkar A, Babu BN, Madhavi YV, Nanduri S (2018) Synthesis of indolo[1,2-b]isoquinoline derivatives by Lewis acid-catalyzed intramolecular Friedel-Crafts alkylation reaction. Eur J Org Chem 2018:2817–2821. https://doi.org/10.1002/ejoc.201800162

    CAS  Article  Google Scholar 

  21. 21.

    Nguyen HH, Fettinger JC, Haddadin MJ, Kurth MJ (2015) Expedient one-pot synthesis of indolo[3,2-c]isoquinolines via a base-promoted N-alkylation/tandem cyclization. Tetrahedron Lett 56:5429–5433. https://doi.org/10.1016/j.tetlet.2015.08.006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Xia Y-Q, Dong L (2017) Ruthenium(II)-catalyzed indolo[2,1-a]isoquinolines synthesis by tandem C–H allylation and oxidative cyclization of 2-phenylindoles with allyl carbonates. Org Lett 19:2258–2261. https://doi.org/10.1021/acs.orglett.7b00762

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Fodor L, Csomós P, Csámpai A, Sohár P (2012) Novel indole syntheses by ring transformation of β-lactam-condensed 1,3-benzothiazines into indolo[2,3-b][1, 4]benzothiazepines and indolo[3,2-c]isoquinolines. Tetrahedron 68:851–856. https://doi.org/10.1016/j.tet.2011.11.036

    CAS  Article  Google Scholar 

  24. 24.

    Qu J, Kumar N, Alamgir M, Black DSC (2009) A versatile synthetic route to 11H-indolo[3,2-c]isoquinolines. Tetrahedron Lett 50:5628–5630. https://doi.org/10.1016/j.tetlet.2009.07.107

    CAS  Article  Google Scholar 

  25. 25.

    Orito K, Miyazawa M, Kanbayashi R, Tokuda M, Suginome H (1999) Synthesis of phthalideisoquinoline and protoberberine alkaloids and indolo[2,1-a]isoquinolines in a divergent route involving palladium(0)-catalyzed carbonylation. J Org Chem 64:6583–6596. https://doi.org/10.1021/jo982451w

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Sharma PMV (2017) Novel synthesis of biologically active indolo[3,2-c]isoquinoline derivatives. Arab J Chem 10:746–749. https://doi.org/10.1016/j.arabjc.2014.07.009

    CAS  Article  Google Scholar 

  27. 27.

    Alicea J, Wolfe JP (2014) Synthesis of substituted tetrahydroindoloisoquinoline derivatives via intramolecular Pd-catalyzed alkene carboamination reactions. J Org Chem 79:4212–4217. https://doi.org/10.1021/jo500470m

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Suarez LL, Greaney MF (2011) Tandem indole C–H alkenylation/arylation for tetra-substituted alkene synthesis. Chem Commun 47:7992–7994. https://doi.org/10.1039/c1cc13094c

    CAS  Article  Google Scholar 

  29. 29.

    Sanz R, Ignacio JM, Castroviejo MP, Fañanás FJ (2007) Synthesis of new indolo[1,2-b]isoquinoline derivatives from N-(2-bromobenzyl)indole. ARKIVOC 2007:84–91. https://doi.org/10.3998/ark.5550190.0008.408

    Article  Google Scholar 

  30. 30.

    Bennasar M-L, Roca T, Ferrando F (2004) Intramolecular reactions of 2-indolylacyl radicals: access to 1,2-fused ring indole derivatives. Org Lett 6:759–762. https://doi.org/10.1021/ol036455l

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Erythropel HC, Zimmerman JB, de Winter TM, Petitjean L, Melnikov F, Lam CH, Lounsbury AW, Mellor KE, Janković NZ, Tu Q, Pincus LN, Falinski MM, Shi W, Coish P, Plata DL, Anastas PT (2018) The green ChemisTREE: 20 years after taking root with the 12 principles. Green Chem 20:1929–1961. https://doi.org/10.1039/c8gc00482j

    CAS  Article  Google Scholar 

  32. 32.

    Tanaka K, Toda F (2000) Solvent-free organic synthesis. Chem Rev 100:1025–1074. https://doi.org/10.1021/cr940089p

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Martins MAP, Frizzo CP, Moreira DN, Buriol L, Machado P (2009) Solvent-free heterocyclic synthesis. Chem Rev 109:4140–4182. https://doi.org/10.1021/cr9001098

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Herrera RP, Marqués-López E (2015) Multicomponent reactions: concepts and applications for design and synthesis. Wiley, Hoboken

    Google Scholar 

  35. 35.

    Singh MS, Chowdhury S (2012) Recent developments in solvent-free multicomponent reactions: a perfect synergy for eco-compatible organic synthesis. RSC Adv 2:4547–4592. https://doi.org/10.1039/c2ra01056a

    CAS  Article  Google Scholar 

  36. 36.

    Kazemizadeh AR, Ali Ramazani (2012) Synthetic applications of Passerini reaction. Curr Org Chem 16:418–450. https://doi.org/10.2174/138527212799499868

    CAS  Article  Google Scholar 

  37. 37.

    Rahmati A, Moazzam A, Khalesi Z (2014) A one-pot four-component synthesis of N-arylidene-2-aryl-imidazo[1,2-a]azin-3-amines. Tetrahedron Lett 55:3840–3843. https://doi.org/10.1016/j.tetlet.2014.03.098

    CAS  Article  Google Scholar 

  38. 38.

    Rahmati A, Ahmadi S, Ahmadi-Varzaneh M (2014) One-pot synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1, 4]diazepine and malonamide derivatives using multi-component reactions. Tetrahedron 70:9512–9521. https://doi.org/10.1016/j.tet.2014.10.060

    CAS  Article  Google Scholar 

  39. 39.

    Beyrati M, Forutan M, Hasaninejad A, Rakovský E, Babaei S, Maryamabadi A, Mohebbi G (2017) One-pot, four-component synthesis of spiroindoloquinazoline derivatives as phospholipase inhibitors. Tetrahedron 73:5144–5152. https://doi.org/10.1016/j.tet.2017.07.005

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge financial support from the Research Council of the University of Isfahan.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Abbas Rahmati.

Ethics declarations

Conflict of interest

Tahmineh Kenarkoohi and Abbas Rahmati confirm that this article content has no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 5667 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kenarkoohi, T., Rahmati, A. An efficient solvent-free synthesis of 2-(alkylamino)-2-oxo-1-arylethyl-6,12-dioxo-6,12-dihydroindolo[1,2-b]isoquinoline-11-carboxylate derivatives via four-component reaction. Mol Divers 23, 1011–1018 (2019). https://doi.org/10.1007/s11030-018-09911-6

Download citation

Keywords

  • Passerini-like reaction
  • Dihydroindole
  • Isoquinoline
  • Isocyanide
  • Indoloisoquinoline