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.

Unified, Asymmetric Total Synthesis of the Asnovolins and Related Spiromeroterpenoids: A Fragment Coupling Approach

“…With scalable access to both fragments, the decisive anionic fragment coupling was next explored. Bis-neopentyl-type 1,2-addition is rare in the literature but is a powerful transformation for assembling molecular complexity .…”

Total Synthesis of Puberuline C

“…Previous efforts focused mainly on the chemical construction of talatisamine ( 2 ) or related structures with the 6/7/5/6/6/5-membered ABCDEF-rings. The Wiesner, Gin, Sarpong, Fukuyama, and Reisman groups reported successful total syntheses of 2 or related C 18 /C 19 -alkaloids by applying distinct and creative methodologies. In 2020, we achieved the total synthesis of 2 , utilizing ring reorganization and oxidative cyclization as the key transformations .…”

Total Synthesis of Poisonous Aconitum Alkaloids Empowered by a Fragment Coupling Strategy

“…It is no mean feat to synthesize such complex natural products as the C 19 diterpene alkaloids (C 19 DTAs), featuring unique polycyclic and bridged structures (Figure ). In this issue of ACS Central Science, Reisman and co-workers take on this considerable challenge, employing a fragment coupling strategy to synthesize (−)-talatisamine ( 1 ), (−)-liljestrandisine ( 2 ), and (−)-liljestrandinine ( 3 ) . A series of highly chemoselective transformations was used to forge the polycyclic bridged skeleton of the natural products, one of which was structurally revised ( 2 vs 4 ).…”