Stereoselective synthesis of indole alkaloids via the application of N-acyliminium ion chemistry

Members of the indole family of alkaloids have long been the subject of scientific investigation. This interest has been stimulated not only by the structural diversity of this family of alkaloids but also because the physiological and biological properties of some are legendary. Our group has developed a facile and highly stereoselective approach to the important indolizino[5,7-b]indole (A) and indolizino[2,3-a]quinolizidine (B) templates from readily available non-racemic substrates. The key ring-forming step involves the cyc1isation of a pendent indole substituent onto an N-acyliminium intermediate. [Illustration omitted.] The potential for application of our novel methodology in target synthesis has been demonstrated by removal of the hydroxymethyl moiety from indolizino[5,7-b]indole and indolizino[2,3-a]quinolizidine derivatives. We have demonstrated the functionalisation of the indolizino[2,3-a]quinolizidine derivatives via conjugate addition chemistry, forming derivatives such as (C), which may be converted to more complex indole alkaloids such as hirsutine (0). We have also utilised our methodology in the asymmetric synthesis of (+)-12b-epidevinylantirhine (E). [Illustration omitted.]