Total Synthesis of (−)-14-Hydroxygelsenicine and Six Biogenetically Related Gelsemium Alkaloids

Abstract

The first concise and collective asymmetric total synthesis of six 14-hydroxygelsenicine-related Gelsemium alkaloids, i.e., 14-hydroxygelsedilam, 14-acetoxygelsedilam, gelsefuranidine, gelsemolenine A, and gelselegandines B and C, was accomplished via the facile construction of a 7-azabicyclo[4.2.1]­nonane skeleton by intramolecular aza-Michael addition, the preparation of an oxabicyclo[3.2.2]­nonane ring core with a secondary hydroxy group at C14 by an intramolecular oxymercuration–hydroxylation strategy, and divergent transformations of 14-hydroxygelsenicine into biogenetically related alkaloids.

Enantioselective Total Syntheses of Lyconadins A–E through a Palladium‐Catalyzed Heck‐Type Reaction

“…To acquire all needed structural skeletons of the seven alkaloids (Scheme ), we planned to explore the potential reactivity of the pivotal intermediate 11 : a) Oxidizing the alcoholic moiety of 11 to the resulting carboxylic acid followed by pyridone formation would afford lyconadin C ( 3 ); b) Converting the amine group of 11 into the corresponding N ‐chloroamine derivative followed by C6 intramolecular nucleophilic attack might provide tetracycle 9 , which bears the core structure of lyconadins A and B ( 1 , 2 ); c) Forming the C4–C13 bond by use of a transannular Mannich‐type reaction highlights nitrone chemistry to give the strained tetracycle 10 , the precursor of lycopodium alkaloids 4 – 7 . Our key intermediate 11 features a bridged seven‐membered‐ring system, which is also found other biologically active natural products . As a result, construction of this bridged seven‐membered‐ring system is clearly the central challenge in the synthesis of these natural products.…”

“…As a result, construction of this bridged seven‐membered‐ring system is clearly the central challenge in the synthesis of these natural products. Previous methods to construct such versatile scaffolds include Michael addition, aza‐Michael addition, Mannich reaction, and ring expansion . Nevertheless, a general protocol to access the bridged seven‐membered‐ring system by employing a transition‐metal‐catalyzed cyclization is scarce.…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…418 Takayama recently described an asymmetric synthesis of (−)-14-hydroxygelsenicine and six other gelsemium alkaloids. 419 The spirooxindole was constructed in a diastereoselective Heck cyclisation (Scheme 80).…”

Total Syntheses of <i>Lycopodium</i> and Monoterpenoid Indole Alkaloids Based on Biosynthesis-Inspired Strategies

“…Further, the divergent transformation of 14-hydroxygelsenicine into biogenetically related Gelsemium alkaloids, i.e., (−)-gelsefuranidine, 53) (−)-gelselegandine B, 65) (−)-gelselegandine C, 65) and (−)-gelsemolenine A, 66) was accomplished recently. 67)…”