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One-pot synthesis of substituted pyrrole–imidazole derivatives with anticancer activity

  • Ming Zhang
  • Yong Ding
  • Hong-Xia Qin
  • Zhi-Gang Xu
  • Hai-Tao LanEmail author
  • Dong-Lin YangEmail author
  • Cheng YiEmail author
Original Article

Abstract

A facile and efficient method to synthesize pyrrole–imidazole was developed via a post-Ugi cascade reaction followed by one purification procedure. Synthesized pyrrole–imidazole was collected by performing a mild reaction and a simple procedure, which could be applicable to a broad scope of functionalized anilines. The screening results demonstrated that compound 7e exhibited a high potency of anticancer activity in human pancreatic cancer cell lines PANC and ASPC-1. Our work shed light on the potential of post-Ugi cascade reaction in combinatorial and medicinal chemistry.

Graphic abstract

Keywords

Pyrrole–imidazole MCRs Microwave irradiation One pot Anticancer activity 

Notes

Acknowledgements

The authors would like to thank the Sichuan Provincial Science and Technology (2017fz0084), the Sichuan Province medical association (s15074), Chongqing Research Program of Basic Research and Frontier Technology (cstc2016jcyjA0534 and cstc2018jcyjAX0219) and the Scientific Research Foundation of the Chongqing University of Arts and Sciences (R2013XY01, R2015BX03, 2017ZBX05 and 2017ZBX10). We would also like to thank Ms H.Z. Liu for obtaining the LC/MS and NMR data.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

11030_2019_9982_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1844 kb)

References

  1. 1.
    Grube A, Köck M (2007) Structural assignment of tetrabromostyloguanidine: does the relative configuration of the palau’amines need revision? Angew Chem Int Ed 46:2320–2324.  https://doi.org/10.1002/anie.200604076 CrossRefGoogle Scholar
  2. 2.
    Lanman BA, Overman LE, Paulini R, White NS (2007) On the structure of palau’amine: evidence for the revised relative configuration from chemical synthesis. J Am Chem Soc 129:12896–12900.  https://doi.org/10.1021/ja074939x CrossRefGoogle Scholar
  3. 3.
    Iwata M, Kamijoh Y, Yamamoto E, Yamanaka M, Nagasawa K (2017) Total synthesis of pyrrole-imidazole alkaloid (+)-cylindradine B. Org Lett 19:420–423.  https://doi.org/10.1021/acs.orglett.6b03722 CrossRefGoogle Scholar
  4. 4.
    Dal Ben D, Antonini I, Buccioni M, Lambertucci C, Marucci G, Thomas A, Volpini R, Cristalli G (2011) Neuropeptide S receptor: recent updates on nonpeptide antagonist discovery. ChemMedChem 6:1163–1171.  https://doi.org/10.1002/cmdc.201100038 CrossRefGoogle Scholar
  5. 5.
    Voss ME, Carter PH, Tebben AJ, Scherle PA, Brown GD, Thompson LA, Xu M, Lo YC, Yang G, Liu R-Q, Strzemienski P, Gerry Everlof J, Trzaskos JM, Decicco CP (2003) Both 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones and 3-thioxo-2,3-dihydro-1H-imidazo[1,5-α]indol-1-ones are light-dependent tumor necrosis factor-α antagonists. Bioorg Med Chem Lett 13:533–538.  https://doi.org/10.1016/S0960-894X(02)00941-1 CrossRefGoogle Scholar
  6. 6.
    Zhang Y, Zheng J, Cui S (2014) Rh(III)-catalyzed C–H activation/cyclization of indoles and pyrroles: divergent synthesis of heterocycles. J Org Chem 79:6490–6500.  https://doi.org/10.1021/jo500902n CrossRefGoogle Scholar
  7. 7.
    Yamawaki I, Matsushita Y, Asaka N, Ohmori K, Nomura N, Ogawa K (1993) Synthesis and aldose reductase inhibitory activity of acetic acid derivatives of pyrrolo[1,2-c]imidazole. Eur J Med Chem 28:481–498.  https://doi.org/10.1016/0223-5234(93)90016-8 CrossRefGoogle Scholar
  8. 8.
    Van-Gelder JM, Klein JY, Basel Y, Reizelman A, Tchilibon S, Mouallem O (2006) Preparation of rhodanine derivatives and analogs thereof as rigidified compounds for modulating heparanase activity. WO2006072953 A2Google Scholar
  9. 9.
    Mishriky N, Asaad FM, Ibrahim YA, Girgis AS (1998) Synthetic approaches towards 1H-pyrrolo[1,2-c]imidazoles. Pharmazie 53:607–611.  https://doi.org/10.1002/chin.199850147 Google Scholar
  10. 10.
    Sharp PP, Banwell MG, Renner J, Lohmann K, Willis AC (2013) Consecutive gold(I)-catalyzed cyclization reactions of o-(Buta-1,3-diyn-1-yl-)-substituted N-Aryl ureas: a one-pot synthesis of pyrimido[1,6-α]indol-1(2H)-ones and related systems. Org Lett 15:2616–2619.  https://doi.org/10.1021/ol4007986 CrossRefGoogle Scholar
  11. 11.
    Fu S, Yang H, Li G, Deng Y, Jiang H, Zeng W (2015) Copper(II)-catalyzed enantioselective intramolecular cyclization of N-alkenylureas. Org Lett 17:1018–1021.  https://doi.org/10.1021/acs.orglett.5b00131 CrossRefGoogle Scholar
  12. 12.
    Katritzky AR, Singh SK, Bobrov S (2004) Novel synthesis of bicycles with fused pyrrole, indole, oxazole, and imidazole rings. J Org Chem 69:9313–9315.  https://doi.org/10.1021/jo0485334 CrossRefGoogle Scholar
  13. 13.
    Wang T, Shi S, Pflästerer D, Rettenmeier E, Rudolph M, Rominger F, Hashmi ASK (2014) Synthesis of polycyclic indole skeletons by a gold(I)-catalyzed cascade reaction. Chem Eur J 20:292–296.  https://doi.org/10.1002/chem.201303539 CrossRefGoogle Scholar
  14. 14.
    Kong W-J, Chen X, Wang M, Dai H-X, Yu J-Q (2018) Rapid syntheses of heteroaryl-substituted imidazo[1,5-α]indole and pyrrolo[1,2-c]imidazole via aerobic C2–H functionalizations. Org Lett 20:284–287.  https://doi.org/10.1021/acs.orglett.7b03596 CrossRefGoogle Scholar
  15. 15.
    Rajesh M, Puri S, Kant R, Reddy MS (2017) Ag-catalyzed intramolecular sequential vicinal diamination of alkynes with isocyanates: synthesis of fused indole-cyclic urea derivatives. J Org Chem 82:5169–5177.  https://doi.org/10.1021/acs.joc.7b00417 CrossRefGoogle Scholar
  16. 16.
    Lei J, Xu Z-G, Li S-Q, Xu J, Zhu J, Chen Z-Z (2016) Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation. Mol Divers 20:859–865.  https://doi.org/10.1007/s11030-016-9679-6 CrossRefGoogle Scholar
  17. 17.
    Li Y, Meng J-P, Lei J, Chen Z-Z, Tang D-Y, Zhu J, Zhang J, Xu Z-G (2017) Efficient synthesis of fused oxazepino-isoquinoline scaffolds via an Ugi, Followed by an intramolecular cyclization. ACS Comb Sci 19:324–330.  https://doi.org/10.1021/acscombsci.7b00002 CrossRefGoogle Scholar
  18. 18.
    Xu Z-G, Ding Y, Meng J-P, Tang D-Y, Li Y, Lei J, Xu C, Chen Z-Z (2018) Facile construction of hydantoin scaffolds via a post-Ugi cascade reaction. Synlett 29:2199–2202.  https://doi.org/10.1055/s-0037-1610234 CrossRefGoogle Scholar
  19. 19.
    McNab H, Tyas RG (2007) A thermal cascade route to pyrroloisoindolone and pyrroloimidazolones. J Org Chem 72:8760–8769.  https://doi.org/10.1021/jo0712502 CrossRefGoogle Scholar
  20. 20.
    Savelli F, Biodo A, Vazzana I, Sparatore F (1987) Tetrahydrocyclopenta[e]pyrido[3,2-b][1,4]diazepine and –cyclopenta[e]pyrido[2,3-b][1,4]diazepine derivatives. J Heterocycl Chem 24:1709–1716.  https://doi.org/10.1002/jhet.5570240641 CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Abdominal Cancer, West China Hospital, West China Clinical Medical SchoolSichuan UniversityChengduChina
  2. 2.Cancer Center, Academy of Medical Sciences and Sichuan Provincial People’s HospitalAffiliated Hospital of University of Electronic Science and Technology of ChinaChengduChina
  3. 3.International Academy of Targeted Therapeutics and InnovationChongqing University of Arts and SciencesChongqingChina

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