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On the formation of a side product with hexahydroaporphine-like structure in the Grewe cyclization of dextromethorphan

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Abstract

Factors leading to the formation of a hexahydroaporphine-like cyclizing side product were studied systematically for the first time and the ratio of this side product was controlled effectively. To understand better the electronic effect of substrates on the formation of side products, different 1-benzyloctahydroisoquinolines with substituted groups on nitrogen or benzene ring were compared. A plausible mechanism of cyclizing reaction was proposed, and key intermediates as well as transition states were analyzed using DFT calculations.

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References

  1. F.C. Tortella, M. Pellicano, N.G. Bowery, Trends Pharmacol. Sci. 10, 501 (1989)

    Article  CAS  Google Scholar 

  2. H.C. Kim, K. Pennypacker, G. Bing, D. Bronstein, M.K. McMillian, J.S. Hong, Neurotoxicology 17, 375 (1996)

    CAS  Google Scholar 

  3. H.C. Kim, H.W. Suh, D. Bronstein, G. Bing, B. Wilson, J.S. Hong, Neuropeptides 31, 105 (1997)

    Article  CAS  Google Scholar 

  4. H.C. Kim, P. H. Lee, W. K. Jhoo, in Symposium on Molecular Monitoring in the Neuroscience Field (Nagoya, Japan), 3, 1 (1998)

  5. H.C. Kim, G. Bing, W.K. Jhoo, K.H. Ko, W.K. Kim, D.C. Lee, E.J. Shin, J.S. Hong, Brain Res. 824, 125 (1999)

    Article  CAS  Google Scholar 

  6. R. Grewe, Naturwissenschaften 33, 333 (1946)

    Article  CAS  Google Scholar 

  7. R. Grewe, A. Mondon, Chem. Ber. 81, 279 (1948)

    Article  CAS  Google Scholar 

  8. R. Grewe, Angew. Chem. 59, 194 (1947)

    Article  Google Scholar 

  9. R. Robinson, S. Sugasawa, J. Chem. Soc. 3163 (1931)

  10. Z. Kitasato, R. Robinson, J. Chem. Soc. 785 (1932)

  11. R. Robinson, S. Sugasawa, J. Chem. Soc. 789 (1932)

  12. R. Robinson, S. Sugasawa, J. Chem. Soc. 280 (1933)

  13. R. Robinson, The Structural Relations of Natural Products (Clarendon Press, Oxford, 1955)

    Google Scholar 

  14. C. Schopf, K. Thierfelder, Ann. Chem. 22, 497 (1932)

    Google Scholar 

  15. C. Schopf, K. Thierfelder, Ann. Chem. 143, 537 (1939)

    Google Scholar 

  16. C. Schopf, Naturwissenschaften 241, 39 (1952)

    Google Scholar 

  17. C. Schopf, H. Perrey, I. Jackh, Ann. Chem. 59, 497 (1932)

    Google Scholar 

  18. O. Schnider, A. Griissner, Helv. Chim. Acta. 821 (1949)

  19. C.F. Koelsch, N.F. Albertson, J. Am. Chem. Soc. 75, 2095 (1953)

    Article  CAS  Google Scholar 

  20. E. Ochiai, M. Ikehara, Pharm. Bull. 2, 109 (1954)

    Article  CAS  Google Scholar 

  21. E. Ochiai, M. Ikehara, Pharm. Bull. 3, 291 (1955)

    Article  Google Scholar 

  22. M. Sasamoto, Chem. Pharm. Bull. 8, 324 (1960)

    Article  CAS  Google Scholar 

  23. A. I. Meyers, T.R. Bailey, J. Org. Chem. 51, 872 (1986)

    Article  CAS  Google Scholar 

  24. H.-T. Tian, L.-J. Ke, Pharm J Today (chinese), 63 (2008)

  25. W. Leimgruber, E. Mohacsi, H. Baruth, L. O. Randall, Raven Press: New York, 8, 45 (1974)

  26. W. Leimgruber, E. Mohacsi, U.S. Patent, 3634429 (1972)

  27. W. Leimgruber, E. Mohacsi, U.S. Patent 3810899 (1974)

  28. E. Mohacsi, U.S. Patent, 4194044 (1980)

  29. K.C. Rice, J. Org. Chem. 45, 3135 (1980)

    Article  CAS  Google Scholar 

  30. P.-X. Wang, F. W. Moser, G. L. Cantrell, C. W. Grote, WO 2008036172A1 (2008)

  31. M. Kitamura, Y. Hsiao, R. Noyori, Tetrahedron Lett. 28, 4829 (1987)

    Article  CAS  Google Scholar 

  32. X.-Q. Wang, F. W. Moser, G. L. Cantrell, J. Bao, U.S. Patent, 7838677 B2 (2010)

  33. C. Witterswil, U.S. Patent, 5905153 (1999)

  34. T. Kumaraguru, N.W. Fadnavis, Org. Process Res. Dev. 18, 174 (2014)

    Article  CAS  Google Scholar 

  35. J. Grussner, J. Hellerbach, A. Brossi, O. Schnider, Helv. Chim. Acta 39, 1371 (1956)

    Article  CAS  Google Scholar 

  36. Y.K. Sawa, K. Kawasaki, S. Mayeda, Pharm. Bull. (Tokyo) 8, 960 (1960)

    Article  CAS  Google Scholar 

  37. H.L. Goering, M.F. Sloan, J. Am. Chem. Soc. 83, 139 (1961)

    Google Scholar 

  38. G.A. Olah, J.M. Bollinger, D.P. Kelly, J. Am. Chem. Soc. 92, 1432 (1970)

    Article  CAS  Google Scholar 

  39. S.A. Monti, S.-C. Chen, Y.-L. Yang, S.-S. Yuan, O.P. Bourgeois, J. Org. Chem. 43, 4062 (1978)

    Article  CAS  Google Scholar 

  40. J. Sakurai, T. Kikuchi, O. Takahashi, K. Watanabe, T. Katoh, Eur. J. Org. Chem. 2948 (2011)

  41. M. Michalak, K. Michalak, Z. Urbanczyk-Lipkowska, J. Wicha, J. Org. Chem. 76, 7497 (2011)

    Article  CAS  Google Scholar 

  42. P.E. Eaton, G.R. Carlson, J.T. Lee, J. Org. Chem. 38, 4071 (1973)

    Article  CAS  Google Scholar 

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Acknowledgments

The work was supported by the National Nature Science Foundation of China (NSFC, 21272069, 20672035), the Fundamental Research Funds for the Central Universities, the Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, the Swedish research council, and the Faculty of science at University of Gothenburg.

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Authors and Affiliations

  1. Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Qiao Zhao, Kai Zhao, Sheng-ying Wu & Li-min Wang

  2. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, 94158, USA

    Sheng-ying Wu & Bo-xue Tian

  3. Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30, Göteborg, Sweden

    Sheng-ying Wu & Leif A. Eriksson

  4. Dongyue Pharma Ltd. Co., Shanghai, People’s Republic of China

    Sheng-ying Wu, Leif A. Eriksson, Na An, Zhong-zhu Long & Shui-hong Cai

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  1. Qiao Zhao
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  2. Kai Zhao
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Correspondence to Li-min Wang.

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Zhao, Q., Zhao, K., Wu, Sy. et al. On the formation of a side product with hexahydroaporphine-like structure in the Grewe cyclization of dextromethorphan. Res Chem Intermed 43, 1689–1708 (2017). https://doi.org/10.1007/s11164-016-2723-4

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  • DOI: https://doi.org/10.1007/s11164-016-2723-4

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