Download PDF
Synthesis 2009(5): 715-720  
DOI: 10.1055/s-0028-1083359
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel and Efficient Synthesis of Dihydrexidine

Juan Pablo Cueva, David E. Nichols*
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA
Fax: +1(765)4941414; e-Mail: drdave@pharmacy.purdue.edu;
Further Information

Publication History

Received 25 September 2008
Publication Date:
11 February 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient synthesis of the dopamine D1 selective full agonist dihydrexidine has been achieved in high yields and requiring no chromatographic separations via a facilitated intramolecular Henry cyclization of a (nitropropyl)benzophenone and subsequent diastereomerically selective reduction of the resulting tricyclic nitroalkene.

Key words

acylations - intramolecular Henry reaction - nitroalkene - total synthesis.

    References

  • 1 Brewster WK. Nichols DE. Riggs RM. Mottola DM. Lovenberg TW. Lewis MH. Mailman RB. J. Med. Chem.  1990,  33:  1756 
    CrossrefPubMedGoogle Scholar
  • 2 Huang X. Lawler CP. Lewis MM. Nichols DE. Mailman RB. Int. Rev. Neurobiol.  2001,  48:  65 
    PubMedGoogle Scholar
  • 3a George MS. Molnar CE. Grenesko EL. Anderson B. Mu Q. Johnson K. Nahas Z. Knable M. Fernandes P. Juncos J. Huang X. Nichols DE. Mailman RB. Schizophr. Res.  2007,  93:  42 
    Google Scholar
  • 3b Goldman-Rakic PS. Castner SA. Svensson TH. Siever LJ. Williams GV. Psychopharmacology (Berl.)  2004,  3 
    Google Scholar
  • 3c Mu Q. Johnson K. Morgan PS. Grenesko EL. Molnar CE. Anderson B. Nahas Z. Kozel FA. Kose S. Knable M. Fernandes P. Nichols DE. Mailman RB. George MS. Schizophr. Res.  2007,  94:  332 
    Google Scholar
  • 3d Nichols DE. Lewis MM. Med. Chem. Res.  2004,  13:  105 
    Google Scholar
  • 4 Ehrlich PP, Michaelides MR, McLaughlin MM, and Hsaio C. inventors; US  5659037. 
  • 5 Negash K. Nichols DE. Tetrahedron Lett.  1996,  37:  6971 
    CrossrefGoogle Scholar
  • 6 Yamashita M. Yamada Ki. Tomioka K. Tetrahedron  2004,  60:  4237 
    CrossrefGoogle Scholar
  • 7 Michaelides MR. Hong Y. DiDomenico S. Bayburt EK. Asin KE. Britton DR. Lin CW. Shiosaki K. J. Med. Chem.  1997,  40:  1585 
    Google Scholar
  • 8 Ghosh D. Nichols DE. Synthesis  1996,  195 
    Article in Thieme ConnectGoogle Scholar
  • 9 Sreekumar R. Padmakumar R. Rugmini P. Tetrahedron Lett.  1998,  39:  2695 
    CrossrefGoogle Scholar
  • 10 Weller T. Seebach D. Davis RE. Laird BB. Helv. Chim. Acta  1981,  64:  736 
    CrossrefGoogle Scholar
  • 11 Haworth RD. Perkin WH. Pink HS. J. Chem. Soc.  1925,  1709 
    Google Scholar
  • 12a Kornblum N. Smiley RA. Blackwood RW. Iffland DC. J. Am. Chem. Soc.  1955,  77:  6269 
    Google Scholar
  • 12b Kornblum N. Cope AC. Org. React.  1962,  12:  101 
    Google Scholar
  • 13 Kornblum N. Blackwood RK. Mooberry DD. J. Am. Chem. Soc.  1956,  78:  1501 
    CrossrefGoogle Scholar
  • 14 Silva PC. Costa JS. Pereira VLP. Synth. Commun.  2001,  31:  595 
    CrossrefGoogle Scholar
  • 15a Angyal SJ. Luttrell BM. Aust. J. Chem.  1970,  23:  1485 
    Google Scholar
  • 15b Zimmerman HE. Nevins TE. J. Am. Chem. Soc.  1957,  79:  6559 
    Google Scholar
  • 16 Knoerzer TA. Nichols DE. Brewster WK. Watts VJ. Mottola D. Mailman RB. J. Med. Chem.  1994,  37:  2453 
    CrossrefPubMedGoogle Scholar
  • 17 TenBrink RE. McCall JM. Johnson HG. J. Med. Chem.  1980,  23:  1058 
    CrossrefPubMedGoogle Scholar
  • 18 Douglas GH. Walk CR. Smith H. J. Med. Chem.  1966,  9:  27 
    CrossrefPubMedGoogle Scholar