Novel routes to kainoids: the total synthesis of (-)-α-kainic acid

摘要

This thesis contains three chapters concerning synthetic studies towards the alkaloids (-)-α-kainic acid; a natural product isolated from the Japanese marine algae Kainin-sou (海人草) or Digenea simplex and the close family member (-)-domoic acid isolated from another Japanese marine algae Doumoi or Chondria armata.ududChapter one gives an introduction to the isolation, structure and biological activity of kainic acid, domoic acid and their analogues. Chapter one also contains a discussion of the previous syntheses of both kainic acid, domoic acid and domoic acid C. It is written with the aim of selecting key aspects of each synthesis and in turn gives a critical account of each piece of work. Chapter two is concerned with the results obtained from the experimental section of this thesis. Disclosed is a novel method for the construction of (-)-α-kainic acid via an ene-reaction on a 1,6-diene intermediate. The synthesis comprises of eight linear steps from readily available D-serine and through the use of simple methodology forms the target compound kainic acid in a satisfactory overall yield of 20 %. This thesis also investigates the possibility of installing a variety of side chains to the biologically active kainoid core via a cross-metathesis reaction on an unsaturated carbon appendage. Chapter three contains the experimental procedures carried out for the synthesis of the compounds discussed in chapter two.