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Synlett 2005(12): 1809-1827  
DOI: 10.1055/s-2005-871575
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© Georg Thieme Verlag Stuttgart · New York

A Review of Advances in the Synthesis of Analogues of the Delphinium ­Alkaloid Methyllycaconitine

Kirsten J. Goodall, David Barker, Margaret A. Brimble*
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland 1020, New Zealand
Fax: +64(9)3737422; e-Mail: m.brimble@auckland.ac.nz;
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Publication History

Received 22 February 2005
Publication Date:
22 June 2005 (online)

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Abstract

Neuronal nicotinic acetylcholine receptors of the α7 sub-type are potential targets for drug development in the treatment of Alzheimer’s disease. The Delphinium alkaloid methyllycaconitine is a potent and selective α7 sub-type selective nicotinic acetylcholine receptor antagonist. The total synthesis of this pharmacologically active alkaloid has not yet been achieved. A summary of semi-synthetic methods to prepare methyllycaconitine is presented. ­Existing synthetic strategies used to prepare E, AE, AEF, ABE, ­ABDE, ABEF ring analogues of methyllycaconitine are reviewed for the first time.

  • 1 Introduction

  • 1.1 Alzheimer’s Disease and α7 Nicotinic Acetylcholine ­Receptors

  • 1.2 Methyllycaconitine - An α7 Subtype Selective Nicotinic Acetylcholine Receptor Antagonist

  • 1.3 Structure-Activity Relationships of Delphinium Alkaloids

  • 2 Semi-Syntheses of Delphinium Alkaloids

  • 3 Synthesis of Analogues of Methyllycaconitine

  • 3.1 Synthesis of E Ring Analogues of Methyllycaconitine

  • 3.2 Synthesis of AE Ring Bicyclic Analogues of Methyl­lycaconitine

  • 3.3 Synthesis of AEF Ring Tricyclic Analogues of Methyl­lycaconitine

  • 3.4 Synthesis of ABE Ring Tricyclic Analogues of Methyl­lycaconitine

  • 3.5 Synthesis of ABDE Ring Tetracyclic Analogues of Methyllycaconitine

  • 3.6 Synthesis of ABEF Ring Tetracyclic Analogues of Methyllycaconitine

  • 4 Conclusion

Key words

semi-synthesis - Delphinium alkaloids - nicotinic acetylcholine receptor α7 sub-type selective antagonists