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Synthesis 2017; 49(09): 1972-1982
DOI: 10.1055/s-0036-1588695
paper
© Georg Thieme Verlag Stuttgart · New York

N,O-Nucleosides from Ene Reaction of (Nitrosocarbonyl)mesitylene with Crotyl Alcohol: Selectivity, Scope, and Limitations

Serena Carosso
a   Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy   Email: paolo.quadrelli@unipv.it
,
Misal Giuseppe Memeo
a   Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy   Email: paolo.quadrelli@unipv.it
,
Bruna Bovio
a   Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy   Email: paolo.quadrelli@unipv.it
,
Elena Valletta
b   Department of System Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Roma, Italy
,
Beatrice Macchi
a   Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy   Email: paolo.quadrelli@unipv.it
,
Paolo Quadrelli*
a   Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy   Email: paolo.quadrelli@unipv.it
› Author Affiliations
Further Information

Publication History

Received: 09 December 2016

Accepted after revision: 09 January 2017

Publication Date:
01 February 2017 (online)

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Abstract

The (nitrosocarbonyl)mesitylene intermediate undergoes an ene reaction with crotyl alcohol, affording two regioisomeric adducts in fair yields. The sterically demanding (nitrosocarbonyl)mesitylene slightly shifts the C2/Markovnikov orientation towards a C3/anti-Markovnikov­ pathway, affording a 5-hydroxyisoxazolidine that serves as a synthon for the preparation of N,O-nucleoside analogues through the Vorbrüggen protocol. The selectivity of the ene reaction is discussed in the light of C=C bond polarization and steric effects. The structures of the N,O-nucleosides are assigned and discussed on the basis of spectroscopic observations and X-ray analysis.

Key words

N,O-nucleosides - ene reaction - nitroso carbonyls - crotyl alcohol - Vorbrüggen protocol

Supporting Information

 

  • References

    • 2a Chiacchio U, Corsaro A, Giofrè S, Romeo G. Isoxazolidinyl Nucleosides . In Chemical Synthesis of Nucleoside Analogues . Merino P. Wiley; Hoboken: 2013
      Google Scholar
    • 2b Romeo R, Giofrè SV, Carnovale C, Chiacchio MA, Campisi A, Mancuso R, Cirmi S, Navarra M. Eur. J. Org. Chem. 2014; 5442
    • 2c Romeo R, Navarra M, Giofrè SV, Carnovale C, Cirmi S, Lanza G, Chiacchio MA. Bioorg. Med. Chem. 2014; 22: 3379
      CrossrefPubMed
    • 2d Romeo R, Carnovale C, Giofrè SV, Moncino G, Chiacchio MA, Sanfilippo C, Macchi B. Molecules 2014; 19: 14406
      CrossrefPubMed
    • 2e Romeo R, Giofrè SV, Carnovale C, Campisi A, Parenti R, Bandini L, Chiacchio MA. Bioorg. Med. Chem. 2013; 21: 7929
      CrossrefPubMed
    • 2f Iannazzo D, Brunaccini E, Giofrè SV, Piperno A, Romeo G, Ronsisvalle S, Chiacchio MA, Lanza G, Chiacchio U. Eur. J. Org. Chem. 2010; 5897
    • 2g Romeo R, Carnovale C, Giofrè SV, Romeo G, Macchi B, Frezza C, Marino-Merlo F, Pistarà V, Chiacchio U. Bioorg. Med. Chem. 2012; 20: 3652
      CrossrefPubMed
    • 2h Romeo R, Giofrè SV, Iaria D, Sciortino MT, Ronsisvalle S, Chiacchio MA, Scala A. Eur. J. Org. Chem. 2011; 5690
    • 2i Kasiganesan H, Wright GL, Chiacchio MA, Gumina G. Bioorg. Med. Chem. 2009; 17: 5347
      CrossrefPubMed
  • 3 Bortolini O, De Nino A, Elioseo T, Gavioli R, Maiuolo L, Russo B, Sforza F. Bioorg. Med. Chem. 2010; 18: 6970
    CrossrefPubMed
    • 4a Boutureira O, Isabel Matheu M, Diaz Y, Castillon S. Chem. Soc. Rev. 2013; 42: 5056
      CrossrefPubMed
    • 4b Grove KL, Guo X, Lui SH, Gao Z, Chu CK, Cheng YC. Cancer Res. 1995; 55: 3008
      PubMed
    • 4c Chang CN, Doong SL, Zhou JH, Beach JW, Jeong LS, Chu CK, Tsai CH, Cheng YC. J. Biol. Chem. 1992; 267: 13938
      PubMed
    • 5a Pistarà V, Corsaro A, Chiacchio MA, Greco G, Quadrelli P. ARKIVOC 2011; (vi): 270
    • 5b Chiacchio U, Genovese F, Iannazzo D, Piperno A, Quadrelli P, Corsaro A, Romeo R, Valveri V, Mastino A. Bioorg. Med. Chem. 2004; 12: 3903
      CrossrefPubMed
    • 5c Chiacchio U, Genovese F, Iannazzo D, Librando V, Merino P, Rescifina A, Romeo R, Propopio A, Romeo G. Tetrahedron 2004; 60: 441
      Crossref
    • 5d Saita MG, Chiacchio U, Iannazzo D, Merino P, Piperno A, Previtera T, Rescifina A, Romeo G, Romeo R. Nucleosides, Nucleotides Nucleic Acids 2003; 22: 739
      CrossrefPubMed
    • 5e Chiacchio U, Corsaro A, Iannazzo D, Piperno A, Pistarà V, Rescifina A, Romeo A, Valveri V, Mastino A, Romeo G. J. Med. Chem. 2003; 46: 3696
      CrossrefPubMed
    • 6a Quadrelli P, Gamba Invernizzi A, Caramella P. Tetrahedron Lett. 1996; 37: 1909
      Crossref
    • 6b Quadrelli P, Mella M, Gamba Invernizzi A, Caramella P. Tetrahedron 1999; 55: 10497
      Crossref
  • 7 Fukuda S, Kamimura A, Kanemasa S, Hori K. Tetrahedron 2000; 56: 1637
    Crossref
    • 8a Quadrelli P, Mella M, Piccanello A, Romano S, Caramella P. J. Org. Chem. 2007; 72: 1807
      CrossrefPubMed
    • 8b Quadrelli P, Romano S, Piccanello A, Caramella P. J. Org. Chem. 2009; 74: 2301
      CrossrefPubMed
    • 8c Adam W, Krebs O. Chem. Rev. 2003; 103: 4131
      CrossrefPubMed
  • 9 Quadrelli P, Mella M, Carosso S, Bovio B. Synthesis 2013; 45: 1414
    Article in Thieme Connect
  • 10 Quadrelli P, Mella M, Caramella P. Tetrahedron Lett. 1998; 39: 3233
    Crossref
    • 11a Motorina IA, Sviridova LA, Golubeva GA, Bundel YG. Tetrahedron Lett. 1989; 30: 117
      Crossref
    • 11b Motorina IA, Sviridova LA, Golubeva GA, Bundel YG. Khim. Geterotsikl. Soedin. 1990; 976
    • 12a Vorbrüggen H, Krolikiewicz K, Bennua-Skalmowski B. US Patent 5,750,676, 1998
    • 12b Vorbrüggen H, Krolikiewicz K, Bennua B. Chem. Ber. 1981; 114: 1234
      Crossref
    • 12c Vorbrüggen H, Höfle G. Chem. Ber. 1981; 114: 1256
      Crossref
    • 12d Vorbrüggen H, Bennua B. Chem. Ber. 1981; 114: 1279
      Crossref
    • 13a Chiacchio U, Corsaro A, Iannazzo D, Piperno A, Pistarà V, Procopio A, Rescifina A, Romeo G, Romeo R, Siciliano MC. R, Valveri E. ARKIVOC 2002; (x): 159
    • 13b Gotkowska J, Balzarini J, Piotrowska DG. Tetrahedron Lett. 2012; 53: 7097
      Crossref

      For acetylation of 5-hydroxyisoxazolidines, see:
    • 14a Xiang Y, Gong Y, Zhao K. Tetrahedron Lett. 1996; 37: 4877
      Crossref
    • 14b Zhang X, Qing F.-L, Yu Y. J. Org. Chem. 2000; 65: 7075
      CrossrefPubMed
    • 14c Zhang X, Xia H, Dong X, Jin J, Meng W.-D, Qing F.-L. J. Org. Chem. 2003; 68: 9026
      CrossrefPubMed
  • 15 Yoshimura Y, Kitano K, Yamada K, Satoh H, Watanabe M, Miura S, Sakata S, Sasaki T, Matsuda A. J. Org. Chem. 1997; 62: 3140
    CrossrefPubMed
  • 16 Caddell JM, Chapman AM, Cooley BE, Downey BP, LeBlanc MP, Jackson MM, O’Connell TM, Phung H.-M, Roper TD, Xie S. J. Org. Chem. 2004; 69: 3112
    CrossrefPubMed
    • 17a Kitade Y, Kojima H, Zulfiqur F, Kim HS, Wataya Y. Bioorg. Med. Chem. Lett. 2003; 13: 3963
      Crossref
    • 17b Ramesh NG, Klunder AJ. H, Zwanenburg B. J. Org. Chem. 1999; 64: 3635
      CrossrefPubMed
    • 17c Wu J, Schneller SW, Seley KL, DeClerq E. Heterocycles 1998; 47: 757
      Crossref
    • 17d Siddiqi SM, Raissian M, Schneller SW, Ikeda S, Snoeck R, Andrei G, Balzarini J, DeClerq E. Bioorg. Med. Chem. Lett. 1993; 3: 663
      Crossref
    • 17e DaSilva AD, Coimbra ES, Fourrey JL, Machado AS, Robert-Gero M. Tetrahedron Lett. 1993; 34: 6745
      Crossref
    • 17f Koga M, Schneller SW. Tetrahedron Lett. 1990; 31: 5861
      Crossref
    • 18a Chiacchio U, Saita MG, Crispino L, Gumina G, Mangiafico S, Pistarà V, Romeo G, Piperno A, De Clercq E. Tetrahedron 2006; 62: 1171
      Crossref
    • 18b Chiacchio U, Iannazzo D, Piperno A, Romeo R, Romeo G, Rescifina A, Saglimbeni M. Bioorg. Med. Chem. 2006; 14: 955
      CrossrefPubMed
  • 19 For a survey on nucleoside synthesis, see: Vorbrüggen H, Ruh-Pohlenz C. Handbook of Nucleoside Synthesis. Wiley; New York: 2001
    Google Scholar
  • 20 Caramella P, Grünager P. 1,3-Dipolar Cycloaddition Chemistry. Vol.1. Padwa A. Wiley; New York: 1984: 291-392 ; and references cited therein
    Google Scholar
    • 21a Gonzalez MP, Teran C, Fall Y, Teijeira M, Besada P. Bioorg. Med. Chem. 2005; 13: 601
      CrossrefPubMed
    • 21b Tchilibon S, Joshi BV, Kim S.-K, Duong HT, Gao Z.-G, Jacobson KA. J. Med. Chem. 2005; 48: 1745
      CrossrefPubMed
    • 21c Joshi BV, Moon HR, Fettinger JC, Marquez VE, Jacobson KA. J. Org. Chem. 2005; 70: 439
      CrossrefPubMed
  • 22 Collins LA, Franzblau SG. Antimicrob. Agents Chemother. 1997; 41: 1004
    CrossrefPubMed
    • 23a Grundmann C, Grünanger P. The Nitrile Oxide. Springer; Heidelberg: 1971
      CrossrefGoogle Scholar
    • 23b Grundmann C, Dean JM. J. Org. Chem. 1965; 30: 2809
      Crossref
  • 24 North AC. T, Phillips DC, Mathews FS. Acta Crystallogr., Sect. A 1968; 24: 351
    Crossref
    • 25a Sheldrick GM. SHELXL-93: Program for Crystal Structure Analysis. University of Göttingen; Germany: 1993
      Google Scholar
    • 25b Johnson CK. ORTEP Report ORNL-3793. Oak Ridge National Laboratory; TN: 1965
      Google Scholar