Total Syntheses of the C19 Diterpenoid Alkaloids (-)-Talatisamine, (-)-Liljestrandisine, and (-)-Liljestrandinine by a Fragment Coupling Approach.

Abstract

The C19 diterpenoid alkaloids (C19 DTAs) are a large family of natural products, many of which modulate the activity of ion channels in vivo and are therefore of interest for the study of neurological and cardiovascular diseases. The complex architectures of these molecules continue to challenge the state-of-the art in chemical synthesis, particularly with respect to efficient assembly of their polcyclic ring systems. Here, we report the total syntheses of (−)-talatisamine, (−)-liljestrandisine, and (−)-liljestrandinine, three aconitine-type C19 DTAs, using a fragment coupling strategy. Key to this approach is a 1,2-addition/semipinacol rearrangement sequence which efficiently joins two complex fragments and sets an all-carbon quaternary center.