Biomimetic and Total Synthesis of Monoterpenoid Isoquinoline Alkaloids

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.