Total Synthesis of (±)-Talatisamine

Key words

(±)-talatisamine - Diels–Alder reaction - [2+2] photo-cycloaddition - Lemieux–Johnson oxidation - retro-aldol–aldol reaction - Wagner–Meerwein rearrangement - aza-Prins reaction

Significance

(–)-Talatisamine is a potassium ion channel inhibitor isolated from an aconitum species. Wiesner and co-workers reported the first total synthesis of (±)‑talatisamine. Its preparation was facilitated by synthetic studies on degradation products of natural (–)-talatisamine. Other diterpene alkaloids prepared by the Wiesner group include atisine and napelline.

Comment

The tricyclic core of (±)-talatisamine is assembled by a Diels–Alder reaction. Ring expansion from the cyclobutane in E via retro-aldol– aldol reaction furnishes the bicyclo[2.2.2]octane motif within F. The atisine-type scaffold G is converted into the delphinine-type skeleton I by Wagner–Meerwein rearrangement in analogy to Wiesner’s biosynthetic proposal. An oxidation followed by aza-Prins reaction furnishes the hexacyclic 6/6/5/6/5/6-membered-ring scaffold of (±)-talatisamine.

Publikationsverlauf

Artikel online veröffentlicht:
11. Mai 2023