title: Strychnine as Target, Samarium Diiodide as Tool: A Personal Story.
abstract: Strychnine stands out from the group of classical natural products as one of the first complex compounds to be isolated in pure form and an extreme challenge to be structurally characterized. It has played a central role in natural product total syntheses and the surge in the development of innovative synthetic methods for many decades. Recently, we have accomplished one of the shortest formal total syntheses of strychnine (in ten steps and 14% overall yield or even shorter in eight steps and 10% overall yield). The evolution of a productive synthetic strategy, as well as the synthetic challenges tackled, are described here in detail, including examples of related transformations. The successful synthetic strategy was inspired by the premise that the core structure could be derived from simple aromatic indole precursors by a reductive SmI2 -induced ketyl-aryl coupling. Other key reactions included a diastereoselective reduction and a regioselective elimination protocol. Altogether one of the shortest syntheses of iso-strychnine and hence of strychnine was established.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology e.V., Hans-Knöll-Institute (HKI), Beutenbergstrasse 11a, 07745, Jena, Germany. christine.beemelmanns@leibniz-hki.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Beemelmanns
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany. hans.reissig@chemie.fu-berlin.de.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Reissig
mesh_terms: D007454:Iodides / Q000737:chemistry*; D015394:Molecular Structure; D012493:Samarium / Q000737:chemistry*; D013331:Strychnine / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D007454:Iodides; D012493:Samarium; D013331:Strychnine; C409809:samarium diiodide
keywords: cascade reactions; natural products; reductive amination; samarium; strychnine