Download PDF
Synthesis 2011(8): 1255-1260  
DOI: 10.1055/s-0030-1258477
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Preparation of Functionalized Isoxazoline Derivatives as Key Intermediates for the Synthesis of Selective N-Methyl-d-aspartate Receptor Antagonists

Lucia Tamborini*a, Andrea Pintoa, Paola Contia, Maddalena Gallantia, Maria Celeste Iannuzzia, Leonardo Lo Prestib, Carlo De Michelia
a Dipartimento di Scienze Farmaceutiche ‘Pietro Pratesi’, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy
Fax: +39(02)50319326; e-Mail: lucia.tamborini@unimi.it;
b Dipartimento di Chimica Fisica ed Elettrochimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy
Further Information

Publication History

Received 10 December 2010
Publication Date:
16 March 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

Two highly versatile isoxazoline derivatives, as key intermediates for the synthesis of differently functionalized subtype-selective N-methyl-d-aspartate receptor antagonists, were designed and synthesized. The synthetic strategy is based on an intramolecular nitrile oxide cycloaddition reaction which is a powerful method capable of controlling both the regio- and stereochemistry of the pericyclic reaction.

Key words

N-methyl-d-aspartate receptor antagonist - intramolecular nitrile oxide cycloaddition - regioselective - isoxazoline - amino acids

    References

  • 1 Dingledine R. Borges K. Bowie D. Traynelis SF. Pharmacol. Rev.  1999,  51:  7 
    Google Scholar
  • 2 Carroll RC. Zukin RS. Trends Neurosci.  2002,  25:  571 
    CrossrefGoogle Scholar
  • 3 Chen H.-SV. Lipton SA. J. Neurochem.  2006,  97:  1611 
    CrossrefGoogle Scholar
  • 4 Paoletti P. Neyton J. Curr. Opin. Pharmacol.  2007,  7:  39 
    CrossrefPubMedGoogle Scholar
  • 5 Conti P. De Amici M. Grazioso G. Roda G. Pinto A. Hansen KB. Nielsen B. Madsen U. Bräuner-Osborne H. Egebjerg J. Vestri V. Pellegrini-Giampietro DE. Sibille P. Acher FC. De Micheli C. J. Med. Chem.  2005,  48:  6315 
    CrossrefPubMedGoogle Scholar
  • 6a Karlsson S. Högberg H.-E. Org. Prep. Proced. Int.  2001,  33:  103 
    Google Scholar
  • 6b Easton CJ. Hughes CMM. Savage GP. Simpson GW. Adv. Heterocycl. Chem.  1994,  60:  261 
    Google Scholar
  • 6c Gallos JK. Koumbis AE. Curr. Org. Chem.  2003,  7:  397 
    Google Scholar
  • 7a Bianchi G. Gandolfi R. In 1,3-Dipolar Cycloaddition Chemistry   Padwa A. John Wiley & Sons; New York: 1984.  p.477 
    Google Scholar
  • 7b Yoshida Y. Ukaji Y. Fujinami S. Inomata K. Chem. Lett.  1998,  10:  1023 
    Google Scholar
  • 7c Askri M. Jgham N. Rammah M. Ciamala K. Monnier-Jobe K. Vebrel J. Heterocycles  2007,  71:  289 
    Google Scholar
  • 8a Caramella P. Grunanger P. Nitrile Oxides and Imines, In 1,3-Dipolar Cycloaddition Chemistry   Vol. 1:  Padwa A. John Wiley & Sons; New York: 1984.  Chap. 3. p.291-392  
    Google Scholar
  • 8b Conti P. De Amici M. Pinto A. Tamborini L. Grazioso G. Frølund B. Nielsen B. Thomsen C. Ebert B. De Micheli C. Eur. J. Org. Chem.  2006,  5533 
    Google Scholar
  • 8c Faita G. Mella M. Mortoni A. Paio A. Quadrelli P. Seneci P. Eur. J. Org. Chem.  2002,  1175 
    Google Scholar
  • 8d Trogu E. De Sarlo F. Machetti F. Chem. Eur. J.  2009,  15:  7940 
    Google Scholar
  • 9a Ramachandiran K. Karthikeyan K. Muralidharan D. Perumal PT. Tetrahedron Lett.  2010,  51:  3006 
    Google Scholar
  • 9b Chapelon A.-S. Giorgi M. Ollivier C. Santelli M. Synth. Commun.  2010,  40:  87 
    Google Scholar
  • 9c Shing TKM. So KH. Kwok WS. Org. Lett.  2009,  11:  5070 
    Google Scholar
  • 9d Kamimura A. Yoshida T. Uno H. Tetrahedron  2008,  64:  11081 
    Google Scholar
  • 9e Vaidya VV. Wankhede KS. Salunkhe MM. Trivedi GK. Synth. Commun.  2008,  38:  2392 
    Google Scholar
  • 9f Nair V. Suja TD. Tetrahedron  2007,  63:  12247 
    Google Scholar
  • 9g Pellissier H. Tetrahedron  2007,  63:  3235 
    Google Scholar
  • 9h Shing TKM. Wong WF. Cheng HM. Kwok WS. So KH. Org. Lett.  2007,  9:  753 
    Google Scholar
  • 9i Xu J. Wang J. Ellis ED. Hamme AT. Synthesis  2006,  3815 
    Google Scholar
  • 9j Shing TKM. Zhong Y.-L. Synlett  2006,  1205 
    Google Scholar
  • 9k Park K.-H. Marshall WJ. Tetrahedron Lett.  2004,  45:  4931 
    Google Scholar
  • 9l Akritopoulou-Zanze I. Gracias V. Moore JD. Djuric SW. Tetrahedron Lett.  2004,  45:  3421 
    Google Scholar
  • 9m Yip C. Handerson S. Tranmer GK. Tam W. J. Org. Chem.  2001,  66:  276 
    Google Scholar
  • 9n Yip C. Handerson S. Jordan R. Tam W. Org. Lett.  1999,  1:  791 
    Google Scholar
  • 10 Mauleon P. Krinsky JL. Toste FD. J. Am. Chem. Soc.  2009,  131:  4513 
    CrossrefPubMedGoogle Scholar
  • 11 O’Donnell MJ. Polt RL. J. Org. Chem.  1982,  47:  2663 
    CrossrefGoogle Scholar
  • 12 Bachi MD. Balanov A. Bar-Ner N. J. Org. Chem.  1994,  59:  7752 
    CrossrefGoogle Scholar
  • 13 Tschaen D. Whittle R. Weinreb S. J. Org. Chem.  1986,  51:  2604 
    CrossrefGoogle Scholar
  • 14 Hassner A. Murthy KSK. Padwa A. Chiacchio U. Dean DC. Schoffstall AM. J. Org. Chem.  1989,  54:  5277 
    CrossrefGoogle Scholar
  • 15 Sheldrick GM. Acta Crystallogr. A  2008,  64:  112 
    CrossrefPubMedGoogle Scholar