Skip to main content
SpringerLink
Log in

A mild and efficient synthesis of monofluorinated α-lactam pseudopeptides via a novel dehydrofluorination of Ugi products

  • Short Communication
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Six novel monofluorinated α-lactam pseudopeptide derivatives were synthesized via Ugi reaction using gem-difluoromethylene-containing isocyanide as a key component, followed by dehydrofluorination of Ugi products in one pot without additional base.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Olson GL, Bolin DR, Bonner MP, Bös M, Cook CM, Fry DC, Graves BJ, Hatada M, Hill DE, Kahn M, Madison VS, Rusiecki VK, Sarabu R, Sepinwall J, Vincent GP, Voss ME (1993) Concepts and progress in the development of peptide mimetics. J Med Chem 36: 3039–3049. doi:10.1021/jm00073a001

    Article  CAS  PubMed  Google Scholar 

  2. Humphrey JM, Chamberlin AR (1997) Chemical synthesis of natural product peptides: coupling methods for the incorporation of noncoded amino acids into peptides. Chem Rev 97: 2243–2266. doi:10.1021/cr950005s

    Article  CAS  PubMed  Google Scholar 

  3. Andronati SA, Karaseva TL, Krysko AA (2004) Peptidomimetics-antagonists of the fibrinogen receptors: molecular design, structures, properties and therapeutic applications. Curr Med Chem 11: 1183–1211. doi:10.2174/0929867043365314

    CAS  PubMed  Google Scholar 

  4. Babine RE, Bender SL (1997) Molecular recognition of protein–ligand complexes: applications to drug design. Chem Rev 97: 1359–1472. doi:10.1021/cr960370z

    Article  CAS  PubMed  Google Scholar 

  5. Qiu X, Meng W, Qing F (2004) Synthesis of fluorinated amino acids. Tetrahedron 60: 6711–6745. doi:10.1016/j.tet.2004.05.051

    Article  CAS  Google Scholar 

  6. Lee HY, Lee KH, Al-Hashimi HM, Marsh ENG (2006) Modulating protein structure with fluorous amino acids: increased stability and native-like structure conferred on a 4-helix bundle protein by hexafluoroleucine. J Am Chem Soc 128: 15556–15557. doi:10.1021/ja0563410

    Article  Google Scholar 

  7. Meng H, Kumar K (2007) Antimicrobial activity and protease stability of peptides containing fluorinated amino acids. J Am Chem Soc 129: 15615–15622. doi:10.1021/ja075373f

    Article  CAS  PubMed  Google Scholar 

  8. Sasaki Y, Yamaguchi K, Tsuji T, Shigenaga A, Fujiib N, Otakaa A (2007) Development of copper-mediated allylation of γ-activated α, β-unsaturated lactam toward peptide mimetic synthesis. Tetrahedron Lett 48: 3221–3224. doi:10.1016/j.tetlet.2007.03.017

    Article  CAS  Google Scholar 

  9. Basak A, Ghosh SC, Dasb AK, Bertolasic V (2005) A novel azetidinyl γ-lactam based peptide with a preference for β-turn conformation. Org Biomol Chem 3: 4050–4052. doi:10.1039/b511029g

    Article  CAS  PubMed  Google Scholar 

  10. Galaud F, Lubell WD (2005) Homoserine-derived cyclic sulfamidate as chiral educt for the diversity-oriented synthesis of lactam-bridged dipeptides. Biopolymers (Pept Sci) 80: 665–674. doi:10.1002/bip.20223

    Article  CAS  Google Scholar 

  11. Miao Y, Gallazzi F, Guo H, Quinn TP (2008) 111In-labeled lactam bridge-cyclized α-melanocyte stimulating hormone peptide analogues for melanoma imaging. Bioconjug Chem 19: 539–547. doi:10.1021/bc700317w

    Article  CAS  PubMed  Google Scholar 

  12. Lung FDT, Chen CH, Liu JH (2005) Development of highly potent and selective dynorphin A analogues as new medicines. J Pept Res 66: 263–276. doi:10.1111/j.1399-3011.2005.00302.x

    Article  CAS  PubMed  Google Scholar 

  13. Elriatil A, Achilles K, Loose J, Otto HH (2007) β-Lactam derivatives as enzyme inhibitors: peptidic derivatives of (R, S)-2-oxo-4-phenylazetidine-1-alkanoic acids. Monatshefte für Chemie 138: 627–634. doi:10.1007/s00706-007-0639-9

    Article  Google Scholar 

  14. Palomo C, Aizpurua JM, Benito A, Miranda JI, Fratila RM, Matute C, Domercq M, Gago F, Martin-Santamaria S, Linden A (2003) Development of a new family of conformationally restricted peptides as potent nucleators of β-turns. Design, synthesis, structure, and biological evaluation of a β-lactam peptide analogue of melanostatin. J Am Chem Soc 125: 16243–16260. doi:10.1021/ja038180a

    Article  CAS  PubMed  Google Scholar 

  15. Alcaide B, Almendros P, Aragoncillo C (2007) β-Lactams: versatile building blocks for the stereoselective synthesis of non-β-lactam products. Chem Rev 107: 4437–4492. doi:10.1021/cr0307300

    Article  CAS  PubMed  Google Scholar 

  16. Maier TC, Podlech J (2004) β-Lactam-containing cyclopeptide analogs. Eur J Org Chem 2004: 4379–4386. doi:10.1002/ejoc.200400295

    Article  Google Scholar 

  17. Talaty ER, Yusoff MM (1998) Regioselectivity in nucleophilic ring-opening of aziridinones. Chem Commun 998: 985–986. doi:10.1039/a800564h

    Article  Google Scholar 

  18. Maran F (1993) Electrochemical and stereochemical investigation on the mechanism of the decay of 2-haloamide anions. The intermediacy of aziridinones. J Am Chem Soc 115: 6557–6563. doi:10.1021/ja00068a012

    Article  CAS  Google Scholar 

  19. Baumgarten HE, Zey RL, Krolls U (1961) Reactions of amines. IX. The rearrangement of N-t-butyl-N-chloroamides. J Am Chem Soc 83: 4469–4470. doi:10.1021/ja01482a041

    Article  CAS  Google Scholar 

  20. Walsh SM, Shah AG, Mond JJ, Lees A, Drabick JJ (2009) Antimicrobial polymer conjugates. http://www.faqs.org/patents/app/20090081180#ixzz0TugMcCde. Accessed 26 Mar 2009

  21. Davies ML, Grunert RR, Haff RF, McGahen JW, Neumayer EM, Paulshock W, Watts JC, IVood TR, Hermann EC, Hoffmann CE (1964) Antiviral activity of 1-adamantanamine (amantadine). Science 144: 862–863. doi:10.1126/science.144.3620.862

    Article  CAS  PubMed  Google Scholar 

  22. Pizzo PA (1993) Management of fever in patients with cancer and treatment induced neutropenia. N Engl J Med 328: 1323–1332

    Article  CAS  PubMed  Google Scholar 

  23. Sheehan JC, Lengyel I (1964) The synthesis and reactions of an α-lactam, 1-t-butyl-3,3-dimethylazirididone. J Am Chem Soc 86: 1356–1359. doi:10.1021/ja01061a018

    Article  CAS  Google Scholar 

  24. Talaty ER, Dupuy AE Jr (1969) Aziridinone derived from 1-aminoadamantane. J Med Chem 12: 195. doi:10.1021/jm00301a062

    Article  CAS  PubMed  Google Scholar 

  25. Cesare V, Lyons TM, Lengyel I (2002) A high-yielding general synthesis of α-lactams. Synthesis 12: 1716–1720. doi:10.1055/s-2002-33652

    Article  Google Scholar 

  26. Liu N, Cao S, Shen L, Wu J, Yu J, Zhang J, Li H, Qian X (2009) New gem-difluoromethylene-containing isocyanide as a useful building block for the synthesis of difluorinated pseudopeptides via Ugi reaction. Tetrahedron Lett 50: 1982–1985. doi:10.1016/j.tetlet.2009.02.056

    Article  CAS  Google Scholar 

  27. Isamu K, Kazumasa F, Masaki M, Hiroshige M, Katsuyoshi S (2008) A facile synthesis of 2-difluoromethyl-6-methylpyridine-3,5-dicarboxylates. Heterocycles 75: 2703–2711. doi:10.1002/chin.200913129

    Article  Google Scholar 

  28. Surmont R, Verniest G, Colpaert F, Macdonald G, Thuring JM, Deroose F, Kimpe ND (2009) New synthesis of 3-fluoropyrroles. J Org Chem 74: 1377–1380. doi:10.1021/jo802272n

    Article  CAS  PubMed  Google Scholar 

  29. Guo Y, Fujiwara K, Amii H, Uneyama K (2007) Selective defluorination approach to N-Cbz-3,3-difluoro-2-difluoromethylenepyrrolidine and its application to 3,3-difluoroproline dipeptide synthesis. J Org Chem 72: 8523–8526. doi:10.1021/jo070719q

    Article  CAS  PubMed  Google Scholar 

  30. Qiu X, Meng W, Qing F (2004) Synthesis of 4-monofluoromethylenyl- and cis-4-monofluoromethyl-l-pyroglutamic acids via a novel dehydrofluorination. Tetrahedron 60: 5201–5206. doi:10.1016/j.tet.2004.04.044

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shanghai Key Laboratory of Chemical Biology, Center of Fluorine Chemical Technology, School of Pharmacy, East China University of Science and Technology, 200237, Shanghai, China

    Nianjin Liu, Song Cao, Jingjing Wu, Li Shen, Jinlong Yu, Jian Zhang, Hui Li & Xuhong Qian

Authors
  1. Nianjin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Song Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingjing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jinlong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xuhong Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Song Cao or Xuhong Qian.

Electronic Supplementary Material

The Below is the Electronic Supplementary Material.

ESM 1 (DOC 3,716 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, N., Cao, S., Wu, J. et al. A mild and efficient synthesis of monofluorinated α-lactam pseudopeptides via a novel dehydrofluorination of Ugi products. Mol Divers 14, 501–506 (2010). https://doi.org/10.1007/s11030-009-9209-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-009-9209-x

Keywords

Search

Navigation