Ring E analogs of methyllycaconitine (MLA) as novel nicotinic antagonists

https://doi.org/10.1016/S0960-894X(99)00378-9Get rights and content

Abstract

We have prepared ring E analogs of the diterpenoid alkaloid methyllycaconitine. These compounds have been assayed for nicotinic activity and were found to act as functional antagonists on adrenal nicotinic receptors.

Novel analogs of methyllycaconitine consisting of only ring E of MLA and the anthranoylsuccinimde side chain have been prepared. One of these analogs shows high affinity for the adrenal nicotinic receptor.

  1. Download : Download full-size image

References (35)

  • D.R.E. Macallan et al.

    FEBS Lett.

    (1988)
  • J.M. Ward et al.

    FEBS Lett.

    (1990)
  • P.A. Coates et al.

    Tetrahedron Lett.

    (1994)
  • G.A. Kraus et al.

    Tetrahedron Lett.

    (1998)
  • W.J. Trigg et al.

    Tetrahedron Lett.

    (1998)
  • G. Grangier et al.

    Tetrahedron Lett.

    (1998)
  • P.A. Coates et al.

    Tetrahedron Lett.

    (1994)
  • J.M. Jacyno et al.

    J. Nat. Prod.

    (1996)
  • D.B. McKay et al.

    J. Pharmacol. Exp. Ther.

    (1984)
  • J. Lindstrom

    Molec. Neurobiol.

    (1997)
  • M.W. Holladay et al.

    J. Med. Chem.

    (1997)
  • D.S. McGehee et al.

    Ann. Rev. Physiol.

    (1995)
  • C.W. Luetje et al.

    J. Neurosci.

    (1991)
  • V. Nambi Aiyar et al.

    Experentia

    (1979)
  • K.R. Jennings et al.

    Experentia

    (1986)
  • S. Wonnacott et al.

    Methods in Neurosciences

    (1993)
  • R.H.F. Manske

    Can. J. Research

    (1938)
  • Cited by (51)

    • Enantioselective synthesis of BE ring analogues of methyllycaconitine

      2016, Tetrahedron
      Citation Excerpt :

      This reaction gave succinimido anthranilates 11a–h as 1:1 mixtures of diastereomers at the C-3″ position. Preparation of enantiopure succinimido anthranilates has previously been achieved via the three step process10q,16 however biological assessment has shown diastereomeric mixtures have similar activity to single isomers.9h,10l The decahydroquinoline BE rings of MLA 1 have an N-ethyl group and we envisaged that this could be introduced by hydrogenolysis of the (R)-α-methyl benzylamine moiety in 7c and subsequent addition of an ethyl moiety.

    • A double Mannich approach to the synthesis of substituted piperidones - Application to the synthesis of substituted E-ring analogues of methyllycaconitine

      2010, Tetrahedron
      Citation Excerpt :

      Functionalised piperidines and piperidones are also important intermediates in the synthesis of numerous other bioactive alkaloids and pharmaceuticals.7 There are few methods for the synthesis of 3,4,5-substituted piperidines,8 with many recent strategies for the synthesis of substituted piperidines aimed particularly at the synthesis of 2-substitued9 and 2,4- and 2,6-disubstitued10 piperidines. We herein report the synthesis of substituted E-ring analogues of methyllycaconitine beginning with a double Mannich reaction of acyclic β-keto esters to form the substituted piperidine ring.

    View all citing articles on Scopus
    View full text