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Synthesis 2012(5): 723-730  
DOI: 10.1055/s-0031-1289688
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Carbocyclic 4-Deazaformycins

Yan Zhang, Wei Ye, Haisheng Wang, Stewart W. Schneller*
The Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, USA
Fax: +1(334)8440239; e-Mail: schnest@auburn.edu;
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Publication History

Received 13 November 2011
Publication Date:
06 February 2012 (online)

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Abstract

The preparation of carbocyclic 4-deazaformycin and its 5′-homoanalogue from a common vinyl precursor, and its N-1 and N-2 methyl derivatives is reported. The syntheses began with a highly stereoselective SN2 reaction between lithio 4-picolines and a protected 2,3-dihydroxy-4-vinylcyclopentyl triflate. The requisite fused pyrazole ring was created by an intramolecular diazonium reaction that was followed by vinyl transformation into the hydroxymethyl and the hydroxyethyl groups. The N-methyl derivatives arose by standard methylation conditions and the resultant N-Me regiochemistry was assigned by homo- and heteronuclear NMR spectroscopy.

Key words

C-nucleosides - carbocyclic nucleosides - pyrazolo[3,4-c]pyridines

    References

  • 1a Adamo MFA. Pergoli R. Curr. Org. Chem.  2008,  12:  1544 
    Search in Google Scholar
  • 1b Stambasky J. Kocek M. Kocovsky P. Chem. Rev.  2009,  109:  6729 
    Search in Google Scholar
  • 1c Simons C. Nucleoside Mimetics: Their Chemistry and Biological Properties   Gordon and Breach; Amsterdam: 2001.  p.127-129  
  • 2a Schneller SW. Curr. Topics Med. Chem.  2002,  2:  1087 
    Search in Google Scholar
  • 2b Herdewijn P. Balzarini J. De Clercq E. Vanderhaeghe H. J. Med. Chem.  1985,  28:  1385 
    Search in Google Scholar
  • 2c De Clercq E. Biochem. Pharmacol.  1987,  36:  2567 
    Search in Google Scholar
  • 2d Cools M. De Clercq E. Biochem. Pharmacol.  1989,  38:  1061 
    Search in Google Scholar
  • 2e Hori M. Ito E. Takita T. Koyama G. Takeuchi T. Umezawa H. J. Antibiot., Ser. A  1964,  17:  96 
    Search in Google Scholar
  • 2f Koyama G. Umezawa H. J. Antibiot., Ser. A  1965,  18:  175 
    Search in Google Scholar
  • 3 Rodriguez JB. Comin MJ. Mini Rev. Med. Chem.  2003,  3:  95 
    Search in Google Scholar
  • 4a Giziewicz J. De Clercq E. Luczak M. Shugar D. Biochem. Pharmacol.  1975,  24:  1813 
    Search in Google Scholar
  • 4b Crabtree GW. Agarwal RP. Parks RE. Lewis AF. Wotring LL. Townsend LB. Biochem. Pharmacol.  1979,  28:  1491 
    Search in Google Scholar
  • 4c Lewis AF. Townsend LB. J. Am. Chem. Soc.  1980,  102:  2817 
    Search in Google Scholar
  • 5a Montgomery JA. Clayton SJ. Thomas HJ. Shannon WM. Arnett G. Bodner AJ. Kion I.-K. Cantoni GL. Chiang PK. J. Med. Chem.  1982,  25:  626 
    Search in Google Scholar
  • 5b Huggins J. Zhang Z.-X. Bray M. J. Infect. Dis.  1999,  179:  S240 
    Search in Google Scholar
  • 6 Yang M. Zhou J. Schneller SW. Tetrahedron  2006,  62:  1295 
    Search in Google Scholar
  • Leading references for carbocyclic C-nucleosides:
  • 7a Boyer SJ. Leahy JW. J. Org. Chem.  1997,  62:  3976 
    Search in Google Scholar
  • 7b Chun BK. Song GY. Chu CK. J. Org. Chem.  2001,  66:  4852 ; and references cited therein
    Search in Google Scholar
  • 7c Tuncbilek M. Schneller SW. Bioorg. Med. Chem.  2003,  11:  3331 
    Search in Google Scholar
  • 7d Zhou J. Yang M. Schneller SW. Tetrahedron Lett.  2004,  45:  8233 
    Search in Google Scholar
  • 7e Zhou J. Yang M. Akdag A. Schneller SW. Tetrahedron  2006,  62:  7009 
    Search in Google Scholar
  • 8 Yang M. Schneller SW. Bioorg. Med. Chem. Lett.  2005,  15:  149 
    Search in Google Scholar
  • 9 Kourafalos VN. Marakos P. Pouli N. Terzis A. Townsend LB. Heterocycles  2002,  12:  2335 
    Search in Google Scholar
  • 11a Marakos P. Pouli N. Wise DS. Townsend LB. Synlett  1997,  561 
  • 11b Kourafalos VN. Marakos P. Pouli N. Townsend LB. Synlett  2002,  1479 
  • 11c Kourafalos VN. Marakos P. Pouli N. Townsend LB. J. Org. Chem.  2003,  68:  6466 
    Search in Google Scholar
  • 11d Korouli S. Lougiakis N. Marakos P. Pouli N. Synlett  2008,  181 
  • 11e Kourafalos VN. Tite T. Mikros E. Marakos P. Pouli N. Balzarini J. Synlett  2008,  3129 
  • 11f Tite T. Lougiakis N. Marakos P. Pouli N. Synlett  2009,  2927 
  • 11g Tite T. Lougiakis N. Myrianthopoulos V. Marakos P. Mikros E. Pouli N. Tenta R. Fragopoulou E. Nomikos T. Tetrahedron  2010,  66:  9620 
    Search in Google Scholar
  • 12 Adapting a procedure reported in: Wang P. Agrofoglio LA. Gary Newton M. Chu CK. Tetrahedron Lett.  1997,  38:  4207 
    Search in Google Scholar
  • 13 Chapman D. Hurst J. J. Chem. Soc., Perkin Trans. 1  1980,  2398 
  • 14 Zemlicka J. J. Am. Chem. Soc.  1975,  97:  5896 
    Search in Google Scholar
10

Crystallographic data (Figure  [³] ) for 25, which was a minor product in the ammonolysis of 12 have been deposited with Cambridge Crystallographic Data Centre (e mail: ccdc@code.cam.ac.uk) and allocated the deposition number CCDC 851387.

Figure 3 Hydrolyis side-product from 12