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Synlett 2011(14): 2009-2012  
DOI: 10.1055/s-0030-1260807
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Elaboration of Peptidomimetics Derived from a PADAM Approach: Synthesis of Polyfunctionalised 2(1H)-Pyrazinones via an Unexpected Aromatisation

Andrea Basso*, Luca Banfi, Giuseppe Guanti, Renata Riva, Paolo Tosatti
Dipartimento di Chimica e Chimica Industriale, Università di Genova, via Dodecaneso 31, 16146 Genova, Italy
Fax: +39(010)3536118; e-Mail: andrea.basso@unige.it;
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Publication History

Received 4 April 2011
Publication Date:
10 August 2011 (online)

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Abstract

When the PADAM (Passerini reaction-amine deprotection-acyl migration) strategy is applied to N-Boc amino acids, the resulting β-acylamino-α-hydroxyamides can be elaborated by secondary-alcohol oxidation, Boc deprotection, and intramolecular ­cyclisation. When TFA is employed to cleave the Boc group a spontaneous aromatisation to 2(1H)-pyrazinones is observed.

Key words

Passerini multicomponent reaction - isocyanides - heterocycles - ring closure - protecting groups - aromatisation

    References and Notes

  • 2 Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005. 
  • 3 Dömling A. Chem. Rev.  2006,  106:  17 
    CrossrefPubMedSearch in Google Scholar
  • 4a Zhu J. Eur. J. Org. Chem.  2003,  1133 
  • 4b Banfi L. Basso A. Riva R. Synlett  2010,  23 
  • 5 Banfi L. Guanti G. Riva R. Chem. Commun.  2000,  985 
  • 6a Banfi L. Guanti G. Riva R. Basso A. Calcagno E. Tetrahedron Lett.  2002,  43:  4067 
    Search in Google Scholar
  • 6b Basso A. Banfi L. Riva R. Piaggio P. Guanti G. Tetrahedron Lett.  2003,  44:  2367 
    Search in Google Scholar
  • 6c Banfi L. Basso A. Guanti G. Riva R. Mol. Diversity  2003,  6:  227 
    Search in Google Scholar
  • 7a Semple JE. Owens TD. Nguyen K. Levy OE. Org. Lett.  2000,  2:  2769 
    Search in Google Scholar
  • 7b Faure F. Hjelmgaard T. Roche SP. Aitken DJ. Org. Lett.  2009,  11:  1167 
    Search in Google Scholar
  • 8 De Moliner F. Crosignani S. Banfi L. Riva R. Basso A. J. Comb. Chem.  2010,  12:  613 
    CrossrefSearch in Google Scholar
  • 10a For the synthesis of 7a-c, see: Wen JJ. Crews CM. Tetrahedron: Asymmetry  1998,  7:  1855 
    Search in Google Scholar
  • 10b

    The absence
    of racemisation was checked by NMR analysis of the corresponding Mosher esters obtained by aldehyde reduction with NaBH4 and subsequent reaction with (R)-Mosher’s chloride. We found that when the reduction with LiAlH4 was performed in THF partial racemisation (5-10%) occurred, whilst complete retention of configuration was observed in Et2O.

  • 11 Banfi L. Riva R. In Organic Reactions   Overman LE. Wiley-VCH; Weinheim: 2005.  p.1 
  • 12a Abellan T. Chinchilla R. Galindo N. Guillena G. Najera C. Sansano JM. Eur. J. Org. Chem.  2000,  2689 
  • 12b Najera C. Abellan T. Sansano JM. Eur. J. Org. Chem.  2000,  2809 
  • 12c Abellan T. Mancheno B. Najera C. Sansano JM. Tetrahedron  2001,  57:  6627 
    Search in Google Scholar
  • 13a Wright AE. Pomponi SS. Cross SS. McCarthy P. J. Org. Chem.  1992,  57:  4772 
    Search in Google Scholar
  • 13b Capon RJ. Rooney F. Murray LM. Collins E. Sim ATR. Rostas JAP. Butler MS. Carroll AR. J. Nat. Prod.  1998,  61:  660 
    Search in Google Scholar
  • 13c Wright AE, Pomponi SA, and Jacobs RS. inventors; WO  9942092.  ; Chem. Abstr. 1999, 131, 175081
  • 13d Cutignano A. Bifulco G. Bruno I. Casapullo A. Gomez-Paloma L. Riccio R. Tetrahedron  2000,  56:  3743 
    Search in Google Scholar
  • 14 Hirano K. Kubota T. Tsuda M. Watanabe K. Fromontc J. Kobayashi J. Tetrahedron  2000,  56:  8107 
    CrossrefSearch in Google Scholar
  • 15a Loosen PK. Tutonda MG. Khorasani MF. Compernolle F. Hoornaert GJ. Tetrahedron  1991,  47:  9259 
    Search in Google Scholar
  • 15b Loosen PK. Khorasani MF. Toppet SM. Hoornaert SM. Tetrahedron  1991,  47:  9269 
    Search in Google Scholar
  • 15c Rombouts FJR. De Borggraeve W. Toppet SM. Compernolle F. Hoornaert GJ. Tetrahedron Lett.  2001,  42:  7397 
    Search in Google Scholar
  • 15d Pawar VG. De Borggraeve WM. Synthesis  2006,  2799 
  • 15e Singh BK. Appukkuttan P. Claerhout S. Parmar VS. Van der Eycken E. Org. Lett.  2006,  8:  1863 
    Search in Google Scholar
  • 15f Garella D. Tagliapietra S. Mehta VP. Van der Eycken E. Cravotto G. Synthesis  2010,  136 
  • For selected examples of bioactive compounds containing the 2(1H)-pyrazinone moiety, see:
  • 16a Janssen PAJ, Van Aken KJA, Lewi PJ, Koymans LMH, De Jonge MR, Heeres J, Daeyaert FFD, Hoornaert GJC, Compernolle FJC, and Kilonda A. inventors; WO  02078708.  ; Chem. Abstr. 2002, 137, 294978
  • 16b Jinsmaa Y. Miyazaki A. Fujita Y. Li T. Fujisawa Y. Shiotani K. Tsuda Y. Yokoi T. Ambo A. Sasaki Y. Bryant SD. Lazarus LH. Okada Y. J. Med. Chem.  2004,  47:  2599 
    Search in Google Scholar
  • 16c Heeres J. de Jonge MR. Koymans LMH. Daeyaert FFD. Vinkers M. Van Aken KJA. Arnold E. Das K. Kilonda A. Hoornaert GJ. Compernolle F. Cegla M. Azzam RA. Andries K. de Béthune M.-P. Azijn H. Pauwels R. Lewi PJ. Janssen PAJ. J. Med. Chem.  2005,  48:  1910 
    Search in Google Scholar
  • 16d Ainge D, Chapman D, Lindsjoe M, Loenn H, Lundkvist M, Munck af Rosenschöld M, Nikitidis A, and Pavey J. inventors; WO  2009061271.  ; Chem. Abstr. 2009, 150, 515208
  • 16e Lu T. Markotan T. Ballentine SK. Giardino EC. Spurlino J. Brown K. Maryanoff BE. Tomczuk BE. Damiano BP. Shukla U. End D. Andrade-Gordon P. Bone RF. Player MR. J. Med. Chem.  2010,  53:  1843 
    Search in Google Scholar
1

Present address: P. Tosatti, School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.

9

We have already applied this concept using the same PG for the α-amino aldehyde and the α-amino acid (ref. 6a).