strychnine and aspidospermidine

A novel approach to prepare the core structure of Aspidosperma and Strychnos alkaloids is described. The strategy is based on a cyclization cascade involving the formation of quaternary carbon center followed by trapping of the radical intermediate by an aryl azide to build the 5-membered ring of the pyrrolocarbazole system. This reaction is run with triethylborane without the need for any hydrogen atom donor such as a tin hydride or tris(trimethylsilyl)silane, and it furnishes the tetracyclic framework as a single diastereomer. The influence of different N-protecting groups on the starting iodoacetamide has been examined.

Topics: Alkaloids; Aspidosperma; Azides; Catalysis; Cyclization; Indole Alkaloids; Iodoacetamide; Molecular Structure; Quinolines; Stereoisomerism; Strychnine; Strychnos

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.

Topics: Alkaloids; Biological Products; Biomimetics; Catalysis; Chemistry, Organic; Cyclization; Indole Alkaloids; Indoles; Quinolines; Research Design; Strychnine