Download PDF
Synthesis 2010(2): 239-248  
DOI: 10.1055/s-0029-1217128
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 5-Amino-1,10b-dihydro-2H-chromeno[3,4-c]pyridine-2,4(3H)-diones from Coumarins and Cyanoacetamides under Basic Conditions

Ornelio Rosati*a, Massimo Curini*a, Maria Carla Marcotullio*a, Gildas Oball-Monda, Caroline Pelucchini*a, Antonio Procopio*b
a Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo, 1, 06123 Perugia (PG), Italy
b Dipartimento Farmaco-Biologico, Università degli Studi della Magna Græcia Complesso Ninì Barbieri, 88021 Roccelletta di Borgia (CZ), Italy
Fax: +39(075)5855116; e-Mail: ornros@unipg.it;
Further Information

Publication History

Received 28 May 2009
Publication Date:
20 November 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

The reaction of various coumarins with cyanoacetamide derivatives under basic conditions (sodium ethoxide, piperidine or 2,2,6,6-tetramethylpiperidine), proceeds via an interesting process which involves skeletal rearrangement of the coumarin, a Michael addition and two cyclizations to afford 5-amino-1,10b-dihydro-2H-chromeno[3,4-c]pyridine-2,4(3H)-diones. The same reaction in the presence of N,N¢-ethane-1,2-diylbis(2-cyanoacetamide) gives the corresponding mono and bis 5-amino-1,10b-dihydro-2H-chromeno[3,4-c]pyridine-2,4(3H)-diones.

Key words

coumarins - Michael addition - heterocycles - cyclizations - chromenes

    References

  • 1 Heravi MM. Bakhtiari K. Zadsirjan V. Bamoharram FF. Heravi OM. Bioorg. Med. Chem. Lett.  2007,  17:  4262 ; and references cited therein
    CrossrefSearch in Google Scholar
  • 2a Kidwai M. Saxena S. Khanb MKR. Thukralb SS. Bioorg. Med. Chem. Lett.  2005,  15:  4295 
    Search in Google Scholar
  • 2b Abd-El-Aziz AS. El-Agrody AM. Bedair AH. Corkery TC. Ata A. Heterocycles  2004,  63:  1793 
    Search in Google Scholar
  • 2c Yavari I. Djahaniani H. Nasiri F. Tetrahedron  2003,  59:  9409 
    Search in Google Scholar
  • 2d Shestopalov AM. Emelianova YuM. Nesterov VN. Russ. Chem. Bull. Int. Ed.  2002,  51:  2238 
    Search in Google Scholar
  • 3 Fujimoto A. Sakurai A. Synthesis  1977,  871 
    Thieme Connect
  • 4 Shi DQ. Wang XS. Tu SJ. Yao CS. Wang YC. Jiegou Huaxue  2002,  21:  60 
    Search in Google Scholar
  • 5 Roudier JF. Foucaud A. Synthesis  1984,  159 
    Thieme Connect
  • 6a Montanari F. Costantino U. Curini M. Rosati O. Nocchetti M. Microporous Mesoporous Mater.  2008,  107:  16 
    Search in Google Scholar
  • 6b Curini M. Epifano F. Chimichi S. Montanari F. Nocchetti M. Rosati O. Tetrahedron Lett.  2005,  46:  3497 
    Search in Google Scholar
  • 7a Curini M. Epifano F. Maltese F. Marcotullio MC. Prieto Gonzales S. Rodriguez JC. Aust. J. Chem.  2003,  56:  59 
    Search in Google Scholar
  • 7b Curini M. Epifano F. Maltese F. Marcotullio MC. Prieto Gonzales S. Rodriguez JC. Tubaro A. Altinier G. Bioorg. Med. Chem. Lett.  2004,  14:  2241 
    Search in Google Scholar
  • 8 Curini M. Rosati O. Marcotullio MC. Montanari F. Campagna V. Pace V. Cravotto G. Eur. J. Org. Chem.  2006,  746 
    Crossref
  • 9 Niefang Y. Aramini JM. Germann MW. Huang Z. Tetrahedron Lett.  2000,  41:  6993 
    CrossrefSearch in Google Scholar
  • 10a Drug Resistance in the Treatment of Cancer   Pinedo HM. Giaccone G. Cambridge University Press; Cambridge: 1998.  p.199 
  • 10b Procopio A. Alcaro S. Cundari S. De Nino A. Ortuso F. Sacchetta P. Pennelli A. Sindona G. J. Med. Chem.  2005,  48:  6084 
    Search in Google Scholar
  • 11a Kiechle FL. Zhang X. Clin. Chim. Acta  2002,  326:  27 
    Search in Google Scholar
  • 11b Folkman J. Semin. Cancer Biol.  2003,  13:  159 
    Search in Google Scholar
  • 11c Reinhold WC. Kouros-Mehr H. Kohn KW. Maunakea AK. Lababidi S. Roschke A. Stover K. Alexander J. Pantazis P. Miller L. Liu E. Kirsch IR. Urasaki Y. Pommier Y. Weinstein JN. Cancer Res.  2003,  63:  1000 
    Search in Google Scholar
  • 12 Xing C. Wang L. Tang XH. Sham YY. Bioorg. Med. Chem.  2007,  15:  2167 
    CrossrefSearch in Google Scholar
  • 13 Gazit A. Osherov N. Posner I. Yaish P. Poradosu E. Gilon C. Levitzki A. J. Med. Chem.  1991,  34:  1896 
    CrossrefSearch in Google Scholar
  • 14 Tattersall PI. Breslin D. Grayson SM. Heath WH. Lou K. McAdams CL. McKean D. Rathsack BM. Willson CG. Chem. Mater.  2004,  16:  1770 
    CrossrefSearch in Google Scholar
  • 15 Gorobets NY. Yousefi BH. Belaj F. Kappe CO. Tetrahedron  2004,  60:  8633 
    CrossrefSearch in Google Scholar
  • 16 Demin P. Rounova O. Grunberger T. Cimpean L. Sharfe N. Roifman CM. Bioorg. Med. Chem.  2004,  12:  3019 
    CrossrefSearch in Google Scholar
  • 17 Devani MB. Shishoo CJ. Pathak US. Parikh SH. Radhakrishnan AV. Padhya AC. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1976,  14:  357 
    Search in Google Scholar
  • 18 Basheer A. Yamataka H. Ammal SC. Rappoport Z. J. Org. Chem.  2007,  72:  5297 
    Search in Google Scholar
  • 20a Gazit A. Osherov N. Gilon C. Levitzki A. J. Med. Chem.  1996,  39:  4905 
    Search in Google Scholar
  • 20b Hill T. Odell LR. Edwards JK. Graham ME. McGeachie AB. Rusak J. Quan A. Abagyan R. Scott JL. Robinson PJ. McCluskey A. J. Med. Chem.  2005,  48:  7781 
    Search in Google Scholar
  • 22a Portugal J. Cashman DJ. Trent JO. Ferrer-Miralles N. Przewloka T. Fokt I. Priebe W. Chaires JB. J. Med. Chem.  2005,  48:  8209 
    Search in Google Scholar
  • 22b Wakelin LPG. Bu X. Eleftheriou A. Parmar A. Hayek C. Stewart BW. J. Med. Chem.  2003,  46:  5790 
    Search in Google Scholar
  • 22c Berge T. Jenkins NS. Hopkirk RB. Waring MJ. Edwardson JM. Henderson RM. Nucleic Acids Res.  2002,  30:  2980 
    Search in Google Scholar
  • 22d Gamage SA. Spicer JA. Finlay GJ. Stewart AJ. Charlton P. Baguley BC. Denny WA. J. Med. Chem.  2001,  44:  1407 
    Search in Google Scholar
19

Supplementary crystallographic data for compounds 10a (CCDC 723518) and 14 (CCDC 723519) can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif

21

Due to the presence of a stereogenic centre on each of the polycyclic units in 15b, 16b and 17b (C-14b and C-14b′), these compounds exist as diastereoisomeric mixtures. The minor structural differences in these sets of diastereoisomers affects the chemical shifts of several of the carbon atoms. These are listed in the ¹³C NMR spectral data as a double peak with a 0.05-0.10 ppm difference in shift, thereby increasing the number of signals overall.