Advertisement

Chemistry of Heterocyclic Compounds

, Volume 54, Issue 6, pp 587–589 | Cite as

Open image in new window Recent methods of 4-quinolone synthesis (microreview)

  • Seyed Sajad Sajadikhah
  • Nesa Lotfifar
Article
  • 20 Downloads

This microreview is devoted to recently reported methods for the synthesis of 4-quinolones including activated alkyne-based reactions, K2CO3/DIPEA-catalyzed reaction, Baylis–Hillman reaction, Pd-catalyzed Buchwald–Hartwig amination, intramolecular Houben–Hoesch reaction, tandem acyl transfer – cyclization of o-alkynoylanilines, fused heterocycle synthesis via double heteroannulation, enaminone-directed C–H amidation, and formation of 4-quinolone moiety as a part of natural products. Microreview covers literature from 2013 to 2017.

Introduction Open image in new window

The synthesis of 4-quinolones exhibiting biological and pharmaceutical activity has attracted attention for more than fifty years.1 The 4-quinolone derivatives have found wide application in the biological and medicinal chemistry as HIV integrase inhibitors, snake venom metalloprotease inhibitors, antimalarial, antitumor, and anti-Helicobacter pylori activity-exhibiting compounds, as well as Na+/K+-ATPase inhibitors and hepatitis C virus NS5B polymerase inhibitors.2 Additionally, 4-quinolone moiety is found in some clinically used antibiotics such as norfloxacin, ofloxacin, levofloxacin, and ciprofloxacin, as well as natural products.3

Activated alkyne-based reactions Open image in new window

A facile and efficient strategy has been reported for the synthesis of substituted 4-quinolones 3 via reaction between 2-(N-tosylamido)benzothioates 1 and activated alkynes 2 in the presence of PPh3 as an inexpensive catalyst.4

Huang et al. reported a practical method for the preparation of 4-oxo-1,4-dihydroquinoline-2-carboxylate 6 using aromatic amines 4 and diethyl acetylenedicarboxylate 5 through hydroamination at ambient temperature followed by PPA-catalyzed intramolecular Friedel–Crafts reaction.5

Another effective method for the synthesis of 4-quinolones 9 has been developed by the means of Cu-catalyzed reaction between N-alkyl- or N-arylanilines 7 and activated alkynes 8 in the presence of triflic acid.6

Open image in new window Seyed Sajad Sajadikhah was born in 1982 in Mamasani, Iran. He obtained his BSc in Pure Chemistry from the University of Isfahan, MSc and PhD in Organic Chemistry under supervision of Prof. M. T. Maghsoodlou from the University of Sistan and Baluchestan, Zahedan. Currently he is a faculty member of the Department of Chemistry at the Payame Noor University, Tehran. His research focused on the heterocyclic chemistry, catalysts, and organic synthesis.

Open image in new window Nesa Lotfifar was born in 1988 in Andimeshk, Khuzestan, Iran. She graduated from the Dezful Islamic Azad University in 2011, received her MSc degree in Organic Chemistry from the Payame Noor University, Esfahan in 2013. At present she is a PhD student at the Payame Noor University, Bushehr. Her scientific interest is heterocyclic chemistry and catalysts.

K 2 CO 3 /DIPEA-catalyzed reaction Open image in new window

One-pot two-step condensation of amides 10 and 3-aryl-3-oxopropanoates 12 gave functionalized 4-quinolones 13 via tandem addition–elimination and nucleophilic aromatic substitution (SNAr) reaction through an imine-enamine tautomerization. In the first step, amide 10 is transformed into reactive imidoyl chloride 11 for acceleration of C–C coupling.7

Baylis–Hillman reaction Open image in new window

A series of 4-quinolone derivatives 16 was obtained in the reaction of Baylis–Hillman adduct 14 and amines 15, which involves aza-Michael addition, SNAr cyclization followed by oxidation using 2-iodoxybenzoic acid.8

Pd-catalyzed Buchwald–Hartwig reaction Open image in new window

Wang et al. developed a new protocol for the synthesis of 4-quinolones 19 in moderate to excellent yields via intermolecular Michael addition reaction between aromatic (Z)-β-chlorovinyl ketones 17 and amines 18, followed by a chloride anion elimination to give enamine intermediates, which are transformed into products 19 in Pd-catalyzed Buchwald–Hartwig reaction. Starting ketones 17 were prepared in the reaction of the corresponding acid chlorides and alkynes in the presence of Fe catalysts.9

Intramolecular Houben–Hoesch reaction Open image in new window

Wu et al. applied triflic anhydride in DMF to synthesize a novel type of 4-quinolones 21 via the intramolecular Houben–Hoesch reaction of β-arylamino acrylonitriles 20 in good to high yields. 2-Cyanoprop-2-enoates 20 were obtained in the reaction of the corresponding cyanoacetate, aryl isothiocyanate, and alkyl bromide catalyzed by K2CO3 in DMF.10

Tandem acyl transfer – cyclization of o -alkynoylanilines Open image in new window

N,N-Diacyl-o-alkynoylanilines 23, formed from N-Boc-2-iodoaniline 22 using N-acylation and carbonylative Sonogashira coupling with phenylacetylene, undergo 9-azajulolidine (9-AJ)-catalyzed tandem acyl transfer – regioselective cyclization to afford trisubstituted 4-quinolones 24 in moderate to good yields.11

Fused heterocycles via double heteroannulation Open image in new window

Chemoselective base-assisted amination of ketene S,N-acetals 25 in dioxane leads to 3-aryl-4-quinolones 26, which can be further transformed into benzothieno[2,3-b]-quinolones 27 under radical cyclization conditions.12

Enaminone-directed C–H amidation Open image in new window

An efficient Co(III)-catalyzed enaminone-directed C–H amidation strategy has been reported by Shi et al. for the synthesis of 7-substituted 4-quinolones 31. The reaction of (E)-1-aryl-3-dimethylaminoprop-2-en-1-ones 28 with 3-ethyl-1,4,2-dioxazol-5-one (29) provided enaminones 30. Nucleophilic attack of amine group on the alkene moiety in compound 30 generates the final products 31.13

Natural products synthesis Open image in new window

Abe et al. reported practical multistep synthesis of intervenolin 35, a natural 4-quinolone, which has shown antitumor activity, from 2-methyl-3-oxo-3-(phenylamino)-propanoic acid (32). The key steps include Suzuki–Miyaura coupling with ester 33 and thiocyanate–isothiocyanate rearrangement of the intermediate 34.14

The first total synthesis of natural product haplacutine C 38 has been reported starting from 1-(2-aminophenyl)ethanone (36) and 4-[(4-methoxybenzyl)oxy]hex-5-enoic acid (37). The intramolecular aldol condensation and Stille coupling reactions were used for the generation of 4-quinolone skeleton and side chain elongation, respectively.15

Notes

Financial support from the Research Council of the Payame Noor University is gratefully acknowleged.

References

  1. 1.
    Naeem, A.; Badshah, S. L.; Muska, M.; Ahmad, N.; Khan, K. Molecules 2016, 21, 268.CrossRefGoogle Scholar
  2. 2.
    (a) Arsenyan, P.; Vasiljeva, J.; Shestakova, I.; Domracheva, I.; Belyakov, S. Chem. Heterocycl. Compd. 2014, 49, 1674. [Khim. Geterotsikl. Soedin. 2013, 1804.] (b) Costi, R.; Métifiot, M.; Chung, S.; Crucitti, G. C.; Maddali, K.; Pescatori, L.; Messore, A.; Madia, V. N.; Pupo, G.; Scipione, L.; Tortorella, S.; Di Leva, F. S.; Cosconati, S.; Marinelli, L.; Novellino, E.; Le Grice, S. F. J.; Corona, A.; Pommier, Y.; Marchand, C.; Di Santo, R. J. Med. Chem. 2014, 57, 3223. (c) Baraldi, P. T.; Magro, A. J.; Matioli, F. F.; Marcussi, S.; Lemke, N.; Calderon, L. A.; Stábeli, R. G.; Soares, A. M.; Correa, A. G.; Fontes, M. R. Biochimie 2016, 121, 179. (d) Šeflová, J.; Čechová, P.; Biler, M.; Hradil, P.; Kubala, M. Biochimie 2017, 138, 56. (e) Cheng, Y.; Shen, J.; Peng, R.-Z.; Wang, G.-F.; Zuo, J.-P.; Long, Y.-Q. Bioorg. Med. Chem. Lett. 2016, 26, 2900.Google Scholar
  3. 3.
    (a) Lee, M.-T. G.; Lee, S.-H.; Chang, S.-S.; Lee, S.-H.; Lee, M.; Fang, C.-C.; Chen, S.-C.; Lee, C.-C. Medicine 2014, 93, 304. (b) Jadulco, R. C.; Pond, C. D.; Wagoner, R. M. V.; Koch, M.; Gideon, O. G.; Matainaho, T. K.; Piskaut, P.; Barrows, L. R. J. Nat. Prod. 2014, 77, 183.Google Scholar
  4. 4.
    Khong, S.; Kwon, O. Asian J. Org. Chem. 2014, 3, 453.CrossRefGoogle Scholar
  5. 5.
    Huang, C.; Guo, J.-H.; Fu, H.-M.; Yuan, M.-L.; Yang, L.-J. Tetrahedron Lett. 2015, 56, 3777.CrossRefGoogle Scholar
  6. 6.
    Xu, X.; Zhang, X. Org. Lett. 2017, 19, 4984.CrossRefGoogle Scholar
  7. 7.
    Lin, J.-P.; Long, Y.-Q. Chem. Commun. 2013, 49, 5313.CrossRefGoogle Scholar
  8. 8.
    Victor, N. J.; Muraleedharan, K. M. Adv. Synth. Catal. 2014, 356, 3600.CrossRefGoogle Scholar
  9. 9.
    Wang, Y.; Liang, H.; Chen, C.; Wang, D.; Peng, J. Synthesis 2015, 1851.Google Scholar
  10. 10.
    Wu, C.; Huang, P.; Sun, Z.; Lin, M.; Jiang, Y.; Tong, J.; Ge, C. Tetrahedron 2016, 72, 1461.CrossRefGoogle Scholar
  11. 11.
    Saito, K.; Yoshida, M.; Uekusa, H.; Doi, T. ACS Omega 2017, 2, 4370.CrossRefGoogle Scholar
  12. 12.
    Janni, M.; Arora, S.; Peruncheralathan, S. Org. Biomol. Chem. 2016, 14, 8781.CrossRefGoogle Scholar
  13. 13.
    Shi, P.; Wang, L.; Chen, K.; Wang, J.; Zhu, J. Org. Lett. 2017, 19, 2418.CrossRefGoogle Scholar
  14. 14.
    Abe, H.; Kawada, M.; Inoue, H.; Ohba, S.-I.; Nomoto, A.; Watanabe, T.; Shibasaki, M. Org. Lett. 2013, 15, 2124.CrossRefGoogle Scholar
  15. 15.
    Kutsumura, N.; Numata, K.; Saito, T. Tetrahedron Lett. 2016, 57, 5581.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryPayame Noor UniversityTehranIran

Personalised recommendations