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Zeitschrift für Naturforschung B

A Journal of Chemical Sciences

12 Issues per year


IMPACT FACTOR 2016: 0.631

SCImago Journal Rank (SJR) 2016: 0.237
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1865-7117
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Volume 71, Issue 10 (Oct 2016)

Issues

Synthesis of morphan derivatives with additional substituents in 8-position

Janine Stefaowitz
  • Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, D-48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dirk Schepmann
  • Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, D-48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Constantin Daniliuc / Susumu Saito / Bernhard Wünsch
  • Corresponding author
  • Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, D-48149 Münster, Germany
  • Cells-in-Motion Cluster of Excellence (EXC 1003 – CiM), Westfälische Wilhelms-Universität Münster, Germany, Tel.: +49-251-8333311, Fax: +49-251-8332144
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-09-22 | DOI: https://doi.org/10.1515/znb-2016-0129

Abstract

The morphan system (2-azabicyclo[3.3.1]nonane) as a substructure of morphine is of major interest in medicinal chemistry. Herein, the synthesis of morphan derivatives with additional substituents at the propano bridge is reported. In order to avoid the isolation of the smelly and volatile nitrile 6 and the very polar primary amine 9, an efficient one-pot, three-step sequential transformation of the mesylate 5 into amides 10 was developed. The key step of the synthesis was the stereoselective intramolecular opening of the epoxides 11ad leading to the exo-configured 8-hydroxymorphans 12ad. The configuration of the exo-configured hydroxymorphan 12d bearing the κ- and σ-pharmacophoric 3,4-dichlorophenylacetyl moiety was inverted by oxidation and stereoselective reduction. An X-ray crystal structure analysis of the benzamide 12c confirmed the relative configuration of the hydroxymorphans 12ad and 14d.

Keywords: intramolecular epoxide opening; inversion of configuration; morphans; nitrile hydration by Ru/chitin catalyst; X-ray crystal structure

Dedicated to: Professor Gerhard Erker on the occasion of his 70th birthday.

References

  • [1]

    A. E. Takemori, P. S. Portoghese, J. Pharmacol. Exp. Ther. 1987, 243, 91.Google Scholar

  • [2]

    A. F. Casy, R. T. Parfitt, Opioid Analgesics – Chemistry and Receptors, Plenum Press, New York 1986.Google Scholar

  • [3]

    E. L. May, J. M. Takeda, J. Med. Chem. 1970, 13, 805.Google Scholar

  • [4]

    W. R. Martin, C. G. Eades, J. A. Thompson, R. E. Huppler, P. E. Gilbert, J. Pharmacol. Exp. Ther. 1976, 197, 517.Google Scholar

  • [5]

    T. Hayashi, S. Y. Tsai, T. Mori, M. Fujimoto, T. P. Su, Expert Opin. Ther. Targets 2011, 15, 557.Google Scholar

  • [6]

    T. Maurice, T. P. Su, Pharmacol. Ther. 2009, 124, 195.Google Scholar

  • [7]

    C. M. Bertha, M. V. Mattson, J. L. Flippen-Anderson, R. B. Rothman, H. Xu, X.-Y. Cha, K. Becketts, K. C. Rice, J. Med. Chem. 1994, 37, 3163.Google Scholar

  • [8]

    K. W. Crawford, W. D. Bowen, Cancer. Res. 2002, 62, 3133.Google Scholar

  • [9]

    J. Bonjoch, F. Diaba, B. Bredshaw, Synthesis 2011, 7, 993.Google Scholar

  • [10]

    M. E. Hediger, Bioorg. Med. Chem. 2004, 12, 4995.Google Scholar

  • [11]

    M.-C. P. Yeh, H.-F. Pai, Z.-J. Lin, B.-R. Lee, Tetrahedron 2009, 65, 4789.Google Scholar

  • [12]

    G. Karig, A. Fuchs, A. Büsing, T. Brandstetter, S. Scherer, J. W. Bats, A. Eschenmoser, G. Quinkert, Helv. Chim. Acta 2000, 83, 1049.Google Scholar

  • [13]

    L. J. Dolby, S. J. Nelson, J. Org. Chem. 1973, 38, 2882.Google Scholar

  • [14]

    W. Bauer, K.-H. Büchel, H. Döpp, T. Eicher, J. Falbe, C. J. Grundmann, H. Hagemann, M. Hanack, D. Klamann, H.-G. Korth, R. P. Kreher, C. Kropf, G. Krüger, K. Kühlein, R. Mayer, H. Pielartzik, M. Regitz, D. Schumann, G. Simchen, R. Sustmann, Houben-Weyl Methods in Organic Chemistry, Vol. E5, Georg Thieme Verlag Stuttgart, 1985, p. 262.Google Scholar

  • [15]

    F. Becke, H. Fleig, P. Päßler, Liebigs Ann. Chem. 1971, 749, 198.Google Scholar

  • [16]

    A. Matsuoka, T. Isogawa, Y. Morioka, B. R. Knappett, A. E. H. Wheatley, S. Saito, H. Naka, R. Soc. Chem. Adv. 2014, 5, 12152.Google Scholar

  • [17]

    S. Knapp, K. E. Rodriques, A. T. Levorse, R. M. Ornaf, Tetrahedron Lett. 1985, 26, 1803.Google Scholar

  • [18]

    S. Knapp, A. T. Levorse, J. Org. Chem. 1988, 53, 4006.Google Scholar

  • [19]

    Y.-Y. Yeung, E. J. Corey, Tetrahedron Lett. 2007, 48, 7567.Google Scholar

  • [20]

    B. Wünsch, C. Geiger in Houbel-Weyl, Science of Synthesis, Vol. 40a, (Eds.: D. Enders, E. Schaumann), Georg Thieme Verlag, Stuttgart, 2009, pp. 23–64.Google Scholar

  • [21]

    C. Bourgeois, E. Werfel, F. Galla, K. Lehmkuhl, H. Torres-Gómez, D. Schepmann, B. Kögel, T. Christoph, W. Straßburger, W. Englberger, M. Soeberdt, S. Hüwel, H.-J. Galla, B. Wünsch J. Med. Chem. 2014, 57, 6845.Google Scholar

  • [22]

    B. R. de Costa, W. D. Bowen, S. B. Hellewell, C. George, R. B. Rothman, A. A. Reid, J. M. Walker, A. E. Jacobson, K. C. Rice, J. Med. Chem. 1989, 32, 1996.Google Scholar

  • [23]

    L. Radesca, W. D. Bowen, L. Di Paolo, B. R. de Costa, J. Med. Chem. 1991, 34, 3058.Google Scholar

  • [24]

    R. N. McDonald, R. N. Steppel, J. E. Dorsey, Org. Synth., Coll. 1988, 6, 276B.Google Scholar

  • [25]

    D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155.Google Scholar

  • [26]

    D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277.Google Scholar

  • [27]

    R. W. W. Hooft, collect, Bruker Analytical X-ray Instruments Inc., Delft (The Netherlands) 2008.Google Scholar

  • [28]

    Z. Otwinowski, W. Minor in Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A (Eds.: C. W. Carter Jr, R. M. Sweet), Academic Press, New York, 1997, pp. 307.Google Scholar

  • [29]

    Z. Otwinowski, D. Borek, W. Majewski, W. Minor, Acta Crystallogr. 2003, A59, 228–234.Google Scholar

  • [30]

    G. M. Sheldrick, Acta Crystallogr. 1990, A46, 467.Google Scholar

  • [31]

    G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112.Google Scholar

  • [32]

    XP – Interactive molecular graphics, (version 5.1), Bruker Analytical X-ray Instruments Inc., Madison, Wisconsin (USA) 1998.Google Scholar

About the article

Received: 2016-05-25

Accepted: 2016-06-10

Published Online: 2016-09-22

Published in Print: 2016-10-01


Citation Information: Zeitschrift für Naturforschung B, ISSN (Online) 1865-7117, ISSN (Print) 0932-0776, DOI: https://doi.org/10.1515/znb-2016-0129.

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