The synthesis of polyfluoroalkyl substituted pyrroles as building blocks for obtaining fluorinated pyrrolidine-containing alkaloids

Authors

  • Anton A. Klipkov V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine; National University of “Kyiv-Mohyla Academy, Ukraine
  • Alexander E. Sorochinsky V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine
  • Karen V. Tarasenko V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine
  • Igor I. Gerus V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0001-5086-9466

DOI:

https://doi.org/10.24959/ophcj.20.199953

Keywords:

enones, amino acids, enaminones, cyclization, polyfluoroalkyl pyrroles

Abstract

Aim. To study the synthetic potential of cyclization of N-(β-polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines into polyfluoroalkyl pyrroles, which are useful intermediates to fluorinated pyrrolidine alkaloids.

Results and discussion. N-(β-Polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines have been obtained and transformed to polyfluoroalkyl-containing pyrroles using acetic or trifluoroacetic anhydride.

Experimental part. N-(β-Polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines were obtained from β-alkoxyvinyl polyfluoroalkyl ketones and the corresponding amino acids. The enaminones so obtained were transformed to polyfluoroalkyl-containing pyrroles with acetic or trifluoroacetic anhydride. The structure and composition of the compounds synthesized were proven by the data of 1Н and 19F NMR spectroscopy and elemental analysis.

Conclusions. It has been shown that an increase of steric hindrance in N-(β-polyfluoroacyl)vinyl derivatives of proline (the perfluoroethyl group instead of the trifluoromethyl group) and N-substituted glycines (replacement of the N-methyl group with the N-benzyl group) gives mainly polyfluoroacyl pyrrolyl acetates when heating in acetic anhydride. Polyfluoroalkyl-containing pyrroles have been obtained by treatment of N-(β-polyfluoroacyl)vinyl derivatives of proline and glycine with trifluoroacetic anhydride.

Received: 01.04.2020
Revised: 05.05.2020
Accepted: 29.05.2020

Supporting Agencies

  • The project of the NAS of Ukraine and Belarus
  • No 0120U101627
  • the theme of the NAS of Ukraine
  • No 0119U100611

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References

  1. Tamariz, J.; Burgueño-Tapia, E.; Vázquez, M. A.; Delgado, F., Chapter One – Pyrrolizidine Alkaloids. In The Alkaloids: Chemistry and Biology; Knölker, H.-J., Ed.; Academic Press: Oxford, 2018; Vol. 80, pp 1–314. https://doi.org/10.1016/bs.alkal.2018.03.001.
  2. Schramm, S.; Köhler, N.; Rozhon, W. Pyrrolizidine Alkaloids: Biosynthesis, Biological Activities and Occurrence in Crop Plants. Molecules 2019, 24, 498. https://doi.org/10.3390/molecules24030498.
  3. Robertson, J.; Stevens, K. Pyrrolizidine alkaloids: occurrence, biology, and chemical synthesis. Nat. Prod. Rep. 2017, 34 (1), 62–89. https://doi.org/10.1039/C5NP00076A.
  4. Nájera, C.; Sansano, J. M. Synthesis of pyrrolizidines and indolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides. Pure Appl. Chem. 2019, 91 (4), 575–596. https://doi.org/10.1515/pac-2018-0710.
  5. Kalaitzakis, D.; Triantafyllakis, M.; Sofiadis, M.; Noutsias, D.; Vassilikogiannakis, G. Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds. Angew. Chem., Int. Ed. Engl. 2016, 55 (14), 4605–4609. https://doi.org/10.1002/anie.201600988.
  6. Ye, L.; Lo, K.-Y.; Gu, Q.; Yang, D. Pd-Catalyzed Intramolecular Aminoalkylation of Unactivated Alkenes: Access to Diverse N-Heterocycles. Org. Lett. 2017, 19 (2), 308–311. https://doi.org/10.1021/acs.orglett.6b03295.
  7. Gouverneur, V.; Seppelt, K. Introduction: Fluorine Chemistry. Chem. Rev. 2015, 115 (2), 563–565. https://doi.org/10.1021/cr500686k.
  8. Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II – III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas. Chem. Rev. 2016, 116 (2), 422–518. https://doi.org/10.1021/acs.chemrev.5b00392.
  9. Huang, Y.; Suzuki, S.; Liu, G.; Tokunaga, E.; Shiro, M.; Shibata, N. Asymmetric synthesis of chiral trifluoromethylated heliotridane via highly catalytic asymmetric Friedel – Crafts alkylation with β-trifluoromethylated acrylates and pyrroles. New J. Chem. 2011, 35 (11), 2614–2621. https://doi.org/10.1039/C1NJ20550A.
  10. Toma, Y.; Kunigami, M.; Watanabe, K. j.; Higashi, M.; Arimitsu, S. One-pot synthesis and theoretical calculation for trifluoromethylated pyrrolizidines by 1,3-dipolar cycloaddition with azomethine ylides and β-trifluoromethyl acrylamides. J. Fluorine Chem. 2016, 189, 22–32. https://doi.org/10.1016/j.jfluchem.2016.07.013.
  11. Klipkov, A. A.; Sorochinsky, A. E.; Tarasenko, K. V.; Rusanova, J. A.; Gerus, I. I. Synthesis of trifluoromethyl and trifluoroacetyl substituted dihydropyrrolizines and tetrahydroindolizines. Tetrahedron Lett. 2020, 61 (12), 151633. https://doi.org/10.1016/j.tetlet.2020.151633.
  12. Gorbunova, M. G.; Gerus, I. I.; Galushko, S. V.; Kukhar, V. P. 4-Ethoxy-1,1,1-trifluoro-3-buten-2-one as a New Protecting Reagent in Peptide Synthesis. Synthesis 1991, 1991 (03), 207–209. https://doi.org/10.1055/s-1991-26420.
  13. Kacharova, L. M.; Gerus, I. I.; Kacharov, A. D. Reaction of α-halogen substituted β-ethoxyvinyl trifluoromethyl ketones with 2-aminopyridine: new route to trifluoroacetyl-containing heterocycles. J. Fluorine Chem. 2002, 117 (2), 193–197. https://doi.org/10.1016/S0022-1139(02)00190-2.
  14. Wöjcik, J.; Domalewski, W.; Kamieńska-Trela, K.; Stefaniak, L.; Vdovienko, S. I.; Gerus, I. I.; Gorbunova, M. G. Conformational behaviour of some trifluoroenaminones by multinuclear magnetic resonance. Magn. Reson. Chem. 1993, 31 (9), 808–814. https://doi.org/10.1002/mrc.1260310904.
  15. Vdovenko, S. I.; Gerus, I. I.; Fedorenko, E. A. The conformational analysis of push – pull enaminoketones using Fourier transform IR and NMR spectroscopy, and quantum chemical calculations: II. β-Dimethylaminoacrolein. Spectrochim. Acta, Part A 2009, 74 (5), 1010–1015. https://doi.org/10.1016/j.saa.2009.08.034.
  16. Shaitanova, E. N.; Gerus, I. I.; Kukhar, V. P. A new synthetic route to 3-polyfluoroalkyl-containing pyrroles. Tetrahedron Lett. 2008, 49 (7), 1184–1187. https://doi.org/10.1016/j.tetlet.2007.12.048.

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Published

2020-06-18

How to Cite

(1)
Klipkov, A. A.; Sorochinsky, A. E.; Tarasenko, K. V.; Gerus, I. I. The Synthesis of Polyfluoroalkyl Substituted Pyrroles As Building Blocks for Obtaining Fluorinated Pyrrolidine-Containing Alkaloids. J. Org. Pharm. Chem. 2020, 18, 23-31.

Issue

Vol. 18 No. 2(70) (2020)

Section

Original Researches

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