Total Synthesis of (–)-Strychnine

Key words

(–)-strychnine - alkaloid - neurotoxin - Tsuji–Trost reaction - carbonylative Stille coupling - aza-Cope/Mannich reaction - Wieland–Gumlich aldehyde

Significance

(–)-Strychnine is a highly neurotoxic plant alkaloid first isolated in 1818 from Strychnos ignatii. Due to the complex structure, it has played a pivotal role in the development of classical structural chemistry and chemical synthesis. The herein highlighted work by Overman and co-workers constitutes the first asymmetric total synthesis of (–)-strychnine.

Comment

One-pot conjugate reduction/triflylation and Pd-catalyzed stannylation furnished organstannane F which served as a key fragment in the ensuing carbonylative Stille coupling with iodide G. A clever solution was devised to deal with the bowl-shaped geometry of tertiary amine K. Aza-Cope/Mannich cascade readily forged the corresponding tricycle in a single step and excellent yield. Further elaboration to (–)-strychnine was achieved via the known Wieland–Gumlich aldehyde.

Publikationsverlauf

Artikel online veröffentlicht:
17. März 2023