Biomimetic and Total Synthesis of Monoterpenoid Isoquinoline Alkaloids

  • R. T. Brown
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

Among the large number of alkaloids containing an isoquinoline nucleus is a small but important group derived from dopamine and a C-9 unit of general type (1). A typical member of the ipecac alkaloids is emetine (3) considered to be formed by condensation of a second dopamine molecule with protoemetine (2). Some years ago this C-9 unit was shown to be monoterpenoid in origin as in the analogous indole alkaloids, the biosynthetic sequence essentially corresponding to that outlined in Fig. 1 (Battersby and Parry 1971, Nagakura et al. 1978). The ultimate non-nitrogenous precursor is the iridoid glucoside secologanin (4). When we discovered a major source of this material in Lonicera spp., we began a programme of partial syntheses of alkaloids using secologanin as starting material, ipecac and related bases being early targets. In general our approach has been “biomimetic”, following wherever possible a likely biosynthetic pathway in an attempt to control the plethora of functional groups and chiral centres. Nevertheless, we have also been able to explore alternative routes and use various chemical strategies to achieve syntheses of both known and potential natural products which are discussed in the first part of this chapter. In the second part we will report on the application of chemical lessons learnt from the above transformations to total syntheses of isoquinoline alkaloids via synthetic analogues of secologanin.

Keywords

Indole Malonate Enol Methoxide Hydrazone 

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References

  1. Battersby AR, Parry RJ (1971) Biosynthesis of the ipecac alkaloids and of ipecoside. J Chem Soc Chem Commun:901–902Google Scholar
  2. Brossi A, Teitel S, Parry GV (1971) In: Manske RHF (ed) The alkaloids, vol XIII, chap 3. Academic, London New York, and references thereinGoogle Scholar
  3. Brown RT (1980) In: Phillipson JD, Zenk MH (eds) Indole and biogenetically related alkaloids. Academic, London New York, pp 171–184Google Scholar
  4. Brown RT (1983) In: Yoshida Z-I, Ise N (eds) Biomimetic chemistry. Kodansha/Elsevier, Amsterdam, p 21Google Scholar
  5. Brown RT, Jones MF (1984) Total synthesis of monoterpenoid isoquinoline alkaloids. Tetrahedron Lett:3127–3130Google Scholar
  6. Brown RT, Pratt SB (1980) Stereoselective synthesis of yohimbine alkaloids from secologanin. J Chem Soc Chem Commun:165–167Google Scholar
  7. Brown RT, Chapple CL, Duckworth DM, Platt R (1976) Conversion of secologanin into elenolic acid and 18-oxayohimban alkaloids. J Chem Soc Perkin 1:160–162CrossRefGoogle Scholar
  8. Brown RT, Lashford AG, Pratt SB (1979) Stereoconservative synthesis of ipecac alkaloids from secologanin. J Chem Soc Chem Commun:367–369Google Scholar
  9. Brown RT, Blackstock WP, Wingfield M (1984) A simple synthetic route to substituted cyclopentenolones. Tetrahedron Lett:1831–1834Google Scholar
  10. Corey EJ, Knapp S (1976) Facile conversion of N,Ndimethylhydrazones to carbonyl compounds by cupric ion-catalyzed hydrolysis. Tetrahedron Lett:3667–3668Google Scholar
  11. Nagakura N, Höfle G, Coggiola D, Zenk MH (1978) The biosynthesis of the ipecac alkaloids and of ipecoside and alangiside. Planta Med 34:381–389CrossRefGoogle Scholar
  12. Sleigh SK (1978) Ph D Thesis, Univ ManchesterGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • R. T. Brown
    • 1
  1. 1.Department of ChemistryUniversity of ManchesterManchesterUK

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