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Synthesis
DOI: 10.1055/a-2788-9051
Paper

Controlled Conversion of C3-Ketoxime Triterpenoids to A-Lactam or A-seco-Nitrile Scaffolds

Authors

  • Catherine Bergeron

    1   Faculty of Pharmacy, Université Laval, Québec, Canada (Ringgold ID: RIN4440)
    2   Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
    3   Centre de recherche en infectiologie, Université Laval, Québec, Canada

  • Christopher Bérubé

    1   Faculty of Pharmacy, Université Laval, Québec, Canada (Ringgold ID: RIN4440)
    2   Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
    3   Centre de recherche en infectiologie, Université Laval, Québec, Canada

  • Maxime Del Mistro

    1   Faculty of Pharmacy, Université Laval, Québec, Canada (Ringgold ID: RIN4440)
    2   Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
    3   Centre de recherche en infectiologie, Université Laval, Québec, Canada

  • Simon Côté

    4   Research and Development, Matrix Innovation Inc., Québec, Canada

  • Dave Richard

    2   Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
    3   Centre de recherche en infectiologie, Université Laval, Québec, Canada
    5   Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université Laval, Québec, Canada (Ringgold ID: RIN4440)

  • Eric Biron 

    1   Faculty of Pharmacy, Université Laval, Québec, Canada (Ringgold ID: RIN4440)
    2   Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
    3   Centre de recherche en infectiologie, Université Laval, Québec, Canada

Natural Sciences and Engineering Research Council of Canada (NSERC) # ALLRP 567473-21
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Graphical Abstract

Abstract

In this work, we report the investigation of several Beckmann rearrangement conditions to selectively produce seven-membered A-lactam and A-seco-nitrile derivatives from triterpenoids. Using C3-oxime–C28-acetate betulin as a model substrate, the presence of zinc chloride in the reaction gave the best yields of either the amide or the ring-opened nitrile products, but the preference between the Beckmann rearrangement versus fragmentation was dictated by the solvent used. The scope of the reaction was extended to other triterpenoids such as lupeol, betulinic acid, and oleanolic acid. Convenient and safe, the reported method was performed on scales up to 20 g, employs cost-effective reagents, and allows the rapid generation of attractive triterpenoid scaffolds and potentially bioactive molecules.

Keywords

Triterpenes - Beckmann rearrangement - Beckmann fragmentation - Lactam-triterpenoids - A-seco-triterpenoids - Lupanes - Oleanes

Supplementary Material



Publication History

Received: 14 November 2025

Accepted after revision: 14 January 2026

Accepted Manuscript online:
14 January 2026

Article published online:
26 January 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Amiri S, Dastghaib S, Ahmadi M. et al. Biotechnol Adv 2020; 38: 39
    Search in Google Scholar
  • 2 Krasutsky PA. Nat Prod Rep 2006; 23: 919-942
    Search in Google Scholar
  • 3 Liu WJ, Li QS, Hu JH, Wang HX, Xu FB, Bian Q. Bioorg Med Chem 2019; 27: 8-15
    Search in Google Scholar
  • 4 Baas WJ. Phytochem 1985; 24: 1875-1889
    Search in Google Scholar
  • 5 Chen IH, Du Y-C, Lu M-C. et al. J Nat Prod 2008; 71: 1352-1357
    Search in Google Scholar
  • 6 Shernyukov AV, Salakhutdinov NF, Tolstikov GA. Russ Chem Bull 2013; 62: 878-895
    Search in Google Scholar
  • 7 Kazakova OB, Medvedeva NI, Tolstikov GA. et al. Mendeleev Commun 2010; 20: 234-236
    Search in Google Scholar
  • 8 Deng Y, Snyder JK. J Org Chem 2002; 67: 2864-2873
    Search in Google Scholar
  • 9 Roy K, Roy R, Raj K, Bhaduri AP. Indian J Chem 1998; 37: 865-867
    Search in Google Scholar
  • 10 Petrova AV, Kazakova OB, Nazarov IS, Csuk R, Heise NV. Chem Biodivers 2023; 20
  • 11 Wei Y, Ma C-M, Hattori M. Eur J Med Chem 2009; 44: 4112-4120
    Search in Google Scholar
  • 12 Tolmacheva IA, Igosheva EV, Savinova OV, Boreko EI, Grishko VV. Chem Nat Compd 2014; 49: 1050-1058
    Search in Google Scholar
  • 13 Romero-Estrada A, Boto A, González-Christen J. et al. J Nat Prod 2022; 85: 787-803
    Search in Google Scholar
  • 14 He X-F, Wang X-N, Yin S, Dong L, Yue J-M. Bioorg Med Chem Lett 2011; 21: 125-129
    Search in Google Scholar
  • 15 Kuczynska K, Bonczak B, Rarova L. et al. J Mol Struct 2022; 1250
  • 16 Huang R, Zhao Y, Wang Y, Zhou L, Chen YF, Wang JF. J Asian Nat Prod Res 2018; 20: 860-866
    Search in Google Scholar
  • 17 Urban M, Sarek J, Klinot J, Korinkova G, Hajduch M. J Nat Prod 2004; 67: 1100-1105
    Search in Google Scholar
  • 18 Kumar S, Misra N, Raj K, Srivastava K, Puri SK. Nat Prod Res 2008; 22: 305-319
    Search in Google Scholar
  • 19 Kazakova OB, Lopatina TV, Baikova IP, Zileeva ZR, Vakhitova YV, Suponitsky KY. Med Chem Res 2020; 29: 1507-1519
    Search in Google Scholar
  • 20 Haavikko R, Nasereddin A, Sacerdoti-Sierra N. et al. Med Chem Commun 2014; 5: 445-451
    Search in Google Scholar
  • 21 Hase T. Acta Chem Scand 1970; 24: 364-365
    Search in Google Scholar
  • 22 Bednarczyk-Cwynar B, Zaprutko L, Froelich AJ. Mol Stuct 2013; 1053: 115-121
    Search in Google Scholar
  • 23 Sundararamaiah T, Ramraj SK, Rao KL, Bai VV. J Indian Chem Soc 1976; 53: 664
    Search in Google Scholar
  • 24 Lopatina TV, Medvedeva NI, Baikova IP, Iskhakov AS, Kazakova OB. Russ J Bioorg Chem 2019; 45: 292-301
    Search in Google Scholar
  • 25 Mazumdar W, Driver TG. Synthesis 2021; 53: 1734-1748
    Search in Google Scholar
  • 26 Smith M. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 7th ed. Hoboken, New Jersey: Wiley; 2013
    Search in Google Scholar
  • 27 Surendra K, Corey EJ. J Am Chem Soc 2009; 131: 13928-13929
    Search in Google Scholar
  • 28 Dehaen W, Mashentseva AA, Seitembetov TS. Molecules 2011; 16: 2443-2466
    Search in Google Scholar
  • 29 Kazakova O, Petrova A, Terekhova A, Vakhitova Y, Polovyanenko D, Bagryanskaya I. ChemistrySelect 2024; 9: e202402593
    Search in Google Scholar
  • 30 Ulici A, Milan A, Mioc M, Ghiulai R, Racoviceanu R, Șoica C. Timiș Med J 2021; 2020: 1
    Search in Google Scholar
  • 31 Kazakova O, Racoviceanu R, Petrova A. et al. Int J Mol Sci 2021; 22: 12542
    Search in Google Scholar
  • 32 Hordyjewska A, Ostapiuk A, Horecka A, Kurzepa J. Phytochem Rev 2019; 18: 929-951
    Search in Google Scholar
  • 33 Augustine JK, Kumar R, Bombrun A, Mandal AB. Tetrahedron Lett 2011; 52: 1074-1077
    Search in Google Scholar
  • 34 Xiao L-F, Xia C-G, Chen J. Tetrahedron Lett 2007; 48: 7218-7221
    Search in Google Scholar
  • 35 Li J-T, Meng X-T, Yin Y. Synth Commun 2010; 40: 1445-1452
    Search in Google Scholar
  • 36 Wiemann J, Heller L, Perl V, Kluge R, Ströhl D, Csuk R. Eur J Med Chem 2015; 106: 194-210
    Search in Google Scholar
  • 37 Gauthier C, Legault J, Lebrun M, Dufour P, Pichette A. Bioorg Med Chem 2006; 14: 6713-6725
    Search in Google Scholar
  • 38 Sun F, Zhu P, Yao H, Wu X, Xu J. J Chem Res 2012; 36: 254-257
    Search in Google Scholar
  • 39 Zhu C, Tang P, Yu B. J Am Chem Soc 2008; 130: 5872-5873
    Search in Google Scholar
  • 40 Carman RM, Cowley DE. Tetrahedron Lett 1964; 5: 627-629
    Search in Google Scholar