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Synthesis 2011(6): 929-933  
DOI: 10.1055/s-0030-1258444
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Total Synthesis of the Natural Carbazoles Glycozolicine, Mukoline, and Mukolidine, Starting from 4,5-Dimethyleneoxazolidin-2-ones

Rafael Bautistaa, Pablo Bernala,b, Luisa E. Montiela, Francisco Delgadoa, Joaquín Tamariz*a
a Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala, 11340 México, D.F., Mexico
Fax: +52(55)57296300/46211; e-Mail: jtamariz@woodward.encb.ipn.mx;
b Departamento de Investigación y Desarrollo, Signa, S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial Toluca, 50200 Toluca, Edo. de México, Mexico
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Publication History

Received 19 November 2010
Publication Date:
18 February 2011 (online)

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Abstract

A novel and efficient synthesis of naturally occurring 1-methoxycarbazoles glycozolicine, mukolidine, and mukoline is developed by applying a regioselective Diels-Alder reaction of a 4,5-dimethyleneoxazolidin-2-one with acrolein. The cycloadduct is transformed to the corresponding functionalized diarylamine. The key palladium-catalyzed cyclization/deformylation cascade reaction of the latter leads to glycozolicine in high overall yield. Oxidation of the C6 methyl group provides the 6-formylcarbazole mukolidine, which is reduced to the respective natural alcohol mukoline.

Key words

1-methoxycarbazoles - 4,5-dimethyleneoxazolidin-2-one - glycozolicine - mukolidine - mukoline - palladium(II) cyclization - decarbonylation

    References

  • 1a Knölker H.-J. Reddy KR. Chemistry and Biology of Carbazole Alkaloids, In The Alkaloids Chemistry and Biology   Vol. 65:  Cordell GA. Academic Press; Amsterdam: 2008. 
    Search in Google Scholar
  • 1b Li WS. McChesney JD. El-Feraly FS. Phytochemistry  1991,  30:  343 
    Search in Google Scholar
  • 1c Fiebig M. Pezzuto JM. Soejarto DD. Kinghorn AD. Phytochemistry  1985,  24:  3041 
    Search in Google Scholar
  • 1d Chakraborty DP. Planta Med.  1980,  39:  97 
    Search in Google Scholar
  • 1e Wu T.-S. Chan Y.-Y. Liou M.-J. Lin F.-W. Shi L.-S. Chen K.-T. Phytother. Res.  1998,  12:  S80 
    Search in Google Scholar
  • 1f Bringmann G. Ledermann A. Holenz J. Kao M.-T. Busse U. Wu HG. François G. Planta Med.  1998,  64:  54 
    Search in Google Scholar
  • 1g Wu T.-S. Huang S.-C. Wu P.-L. Teng C.-M. Phytochemistry  1996,  43:  133 
    Search in Google Scholar
  • 1h Chakraborty A. Chowdhury BK. Bhattacharyya P. Phytochemistry  1995,  40:  295 
    Search in Google Scholar
  • 1i Chakraborty A. Saha C. Podder G. Chowdhury BK. Bhattacharyya P. Phytochemistry  1995,  38:  787 
    Search in Google Scholar
  • 1j Bringmann G. Ledermann A. François G. Heterocycles  1995,  40:  293 
    Search in Google Scholar
  • 1k Knölker H.-J. Reddy KR. Chem. Rev.  2002,  102:  4303 
    Search in Google Scholar
  • 1l Nayak A. Mandal S. Banerji A. Banerji J. J. Chem. Pharm. Res.  2010,  2:  286 
    Search in Google Scholar
  • 2a Chakraborty DP. Bhattacharyya P. Roy S. Bhattacharyya SP. Biswas AK. Phytochemistry  1978,  17:  834 
    Search in Google Scholar
  • 2b Chowdhury BK. Chakraborty DP. Chem. Ind. (London)  1969,  549 
  • 2c Wu T.-S. Huang S.-C. Wu P.-L. Kuoh C.-S. Phytochemistry  1999,  52:  523 
    Search in Google Scholar
  • 3a Chakraborty DP. Barman BK. Bose PK. Tetrahedron  1965,  21:  681 
    Search in Google Scholar
  • 3b Bhattacharyya P. Chakraborty DP. Phytochemistry  1973,  12:  1831 
    Search in Google Scholar
  • 4a Chowdhury BK. Chakraborty DP. Phytochemistry  1971,  10:  1967 
    Search in Google Scholar
  • 4b Sukari MA. Ahmad K. Haron MJ. Muse R. Malaysian J. Anal. Sci.  2001,  7:  263 
    Search in Google Scholar
  • For recent examples:
  • 5a Choshi T. Sada T. Fujimoto H. Nagayama C. Sugino E. Hibino S. J. Org. Chem.  1997,  62:  2535 
    Search in Google Scholar
  • 5b Fröhner W. Krahl MP. Reddy KR. Knölker H.-J. Heterocycles  2004,  63:  2393 
    Search in Google Scholar
  • 5c Knölker H.-J. Curr. Org. Synth.  2004,  1:  309 
    Search in Google Scholar
  • 5d Appukkuttan P. Van der Eycken E. Dehaen W. Synlett  2005,  127 
  • 5e Liu C.-Y. Knochel P. Org. Lett.  2005,  7:  2543 
    Search in Google Scholar
  • 5f Tsang WCP. Zheng N. Buchwald SL. J. Am. Chem. Soc.  2005,  127:  14560 
    Search in Google Scholar
  • 5g Scott TL. Yu X. Gorugantula SP. Carrero-Martínez G. Söderberg BCG. Tetrahedron  2006,  62:  10835 
    Search in Google Scholar
  • 5h Kitawaki T. Hayashi Y. Ueno A. Chida N. Tetrahedron  2006,  62:  6792 
    Search in Google Scholar
  • 5i Liger F. Popowycz F. Besson T. Picot L. Galmarini CM. Joseph B. Bioorg. Med. Chem.  2007,  15:  5615 
    Search in Google Scholar
  • 5j Jordan-Hore JA. Johansson CCC. Gulias M. Beck EM. Gaunt MJ. J. Am. Chem. Soc.  2008,  130:  16184 
    Search in Google Scholar
  • 5k Li B.-J. Tian S.-L. Fang Z. Shi Z.-J. Angew. Chem. Int. Ed.  2008,  47:  1115 
    Search in Google Scholar
  • 5l Knölker H.-J. Chem. Lett.  2009,  38:  8 
    Search in Google Scholar
  • 5m Stokes BJ. Jovanovic B. Dong H. Richert KJ. Riell RD. Driver TG. J. Org. Chem.  2009,  74:  3225 
    Search in Google Scholar
  • 5n Watanabe T. Oishi S. Fujii N. Ohno H. J. Org. Chem.  2009,  74:  4720 
    Search in Google Scholar
  • For examples of synthesis of 1-oxygenated carbazoles, see:
  • 6a Knölker H .-J. Bauermeister M. Tetrahedron  1993,  49:  11221 
    Search in Google Scholar
  • 6b Bringmann G. Tasler S. Endress H. Peters K. Peters E.-M. Synthesis  1998,  1501 
  • 6c Brenna E. Fuganti C. Serra S. Tetrahedron  1998,  54:  1585 
    Search in Google Scholar
  • 6d Bringmann G. Tasler S. Tetrahedron  2001,  57:  2337 
    Search in Google Scholar
  • 6e Knölker H.-J. Wolpert M. Tetrahedron  2003,  59:  5317 
    Search in Google Scholar
  • 6f Kuwahara A. Nakano K. Nozaki K. J. Org. Chem.  2005,  70:  413 
    Search in Google Scholar
  • 6g Mal D. Senapati B. Pahari P. Tetrahedron Lett.  2006,  47:  1071 
    Search in Google Scholar
  • 6h Campeau L.-C. Parisien M. Jean A. Fagnou K. J. Am. Chem. Soc.  2006,  128:  581 
    Search in Google Scholar
  • 6i Sridharan V. Martin MA. Menéndez JC. Synlett  2006,  2375 
  • 6j Tohyama S. Choshi T. Azuma S. Fujioka H. Hibino S. Heterocycles  2009,  79:  955 
    Search in Google Scholar
  • 7 Mandal AB. Delgado F. Tamariz J. Synlett  1998,  87 
    Thieme Connect
  • 8a Zempoalteca A. Tamariz J. Heterocycles  2002,  57:  259 
    Search in Google Scholar
  • 8b Benavides A. Peralta J. Delgado F. Tamariz J. Synthesis  2004,  2499 
  • 9 Bernal P. Benavides A. Bautista R. Tamariz J. Synthesis  2007,  1943 
    Thieme Connect
  • 10 Mandal AB. Gómez A. Trujillo G. Méndez F. Jiménez HA. Rosales MJ. Martínez R. Delgado F. Tamariz J. J. Org. Chem.  1997,  62:  4105 
    CrossrefSearch in Google Scholar
  • 11 Jash SS. Biswas GK. Bhattacharyya SK. Bhattacharyya P. Chakraborty A. Chowdhury BK. Phytochemistry  1992,  31:  2503 
    CrossrefSearch in Google Scholar
  • 12 Chakravarty AK. Sarkar T. Masuda K. Takey T. Doi H. Kotani E. Shiojima K. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  2001,  40:  484 
    Search in Google Scholar
  • 13 Randelia BE. Patel BPJ. Experientia  1982,  38:  529 
    CrossrefSearch in Google Scholar
  • 14 Roy S. Bhattacharyya L. Chakraborty DP. J. Indian Chem. Soc.  1982,  59:  1369 
    Search in Google Scholar
  • 15 Wei LS. Musa N. Sengm CT. Wee W. Shazili NAM. Afr. J. Biotechnol.  2008,  7:  2275 
    Search in Google Scholar
  • 16a Tsuji J. Ohno K. J. Am. Chem. Soc.  1968,  90:  94 
    Search in Google Scholar
  • 16b Tsuji J. Ohno K. Synthesis  1969,  157 
  • 16c Kozikowski AP. Wetter HF. Synthesis  1976,  561 
  • 16d Thompson DJ. Carbonylation and Decarbonylation, In Comprehensive Organic Synthesis   Vol. 3:  Trost B. Fleming I. Pergamon Press; Oxford: 1991.  p.1015-1043  
    Search in Google Scholar
  • 16e Murakami M. Ito Y. Top. Organomet. Chem.  1999,  3:  97 
    Search in Google Scholar
  • 17 Åkermark B. Eberson L. Jonsson E. Pettersson E. J. Org. Chem.  1975,  40:  1365 
    CrossrefSearch in Google Scholar
  • 18a Smolík J. Kraus M. Collect. Czech. Chem. Commun.  1972,  37:  3042 
    Search in Google Scholar
  • 18b Demopoulos BJ. Anderson HJ. Loader CE. Faber K. Can. J. Chem.  1983,  61:  2415 
    Search in Google Scholar
  • 18c Peroutková V. Beránek L. Collect. Czech. Chem. Commun.  1976,  41:  526 
    Search in Google Scholar
  • 18d Lejemble P. Maire Y. Gaset A. Kalck P. Chem. Lett.  1983,  1403 
  • 19 Hawthorne JO. Wilt MH. J. Org. Chem.  1960,  25:  2215 
    CrossrefSearch in Google Scholar
  • 20 Krahl MP. Jäger A. Krause T. Knölker H.-J. Org. Biomol. Chem.  2006,  4:  3215 
    CrossrefPubMedSearch in Google Scholar
  • 21a Hagelin H. Oslob JD. Åkermark B. Chem. Eur. J.  1999,  5:  2413 
    Search in Google Scholar
  • 21b Sridharan V. Martín MA. Menéndez JC. Eur. J. Org. Chem.  2009,  4614 
  • 22 Schmidt M. Knölker H.-J. Synlett  2009,  2421 
    Thieme Connect
  • The catalytic cycle for the ring-closure conversion of the diarylamine into the carbazole framework was firstly described by Knölker and co-workers:
  • 23a Knölker H.-J. O’Sullivan N. Tetrahedron  1994,  50:  10893 
    Search in Google Scholar
  • 23b Knölker H.-J. Fröhner W. J. Chem. Soc., Perkin Trans. 1  1998,  173 
  • 23c Knölker H.-J. Fröhner W. Reddy KR. Synlett  2002,  557 
  • 23d Knölker H.-J. Reddy KR. Heterocycles  2003,  60:  1049 
    Search in Google Scholar
  • 23e Forke R. Krahl MP. Krause T. Schlechtingen G. Knölker H.-J. Synlett  2007,  268