Die Totalsynthese von Lodopyridon

Die Entdeckung von Lodopyridon, einem strukturell einzigartigem Alkaloid, wurde 2009 von Fenical et al. berichtet. Der Naturstoff wurde aus dem Actinomyceten Saccharomonospora sp. CNQ490 isoliert, der in Sedimenten des „La Jolla Submarine Canyon“ vor der Küste Kaliforniens gefunden wurde. Die vorli...

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Bibliographic Details
Main Author: Burckhardt, Tobias
Contributors: Koert, Ulrich (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2013
Online Access:PDF Full Text
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The discovery of lodopyridone, a structurally unprecedented alkaloid, was reported by Fenical et al. in 2009. It was isolated from the marine derived Saccharomonospora sp. CNQ490, that had been found in the muddy sediments near the mouth of the La Jolla Submarine Canyon (CA, USA). In this thesis the first total synthesis of lodopyridone is reported. The synthetic strategy was based on a late cross-coupling of an iodopyridone with an chloroquinoline-thiazolyl tin compound. The synthesis of the pentasubstituted pyridone-core was accomplished by a regioselective bromination of a 4 pyridone derived from kojic acid. A subsequent Cu-mediated introduction of the thiomethylether and a directed lithiation/iodination step gave the iodopyridone, that allowed the coupling to the target molecule. A chemoselective Negishi cross-coupling of 2,4 dibromothiazole and a quinolinylzinc reagent was used to assemble the chloroquinolinethiazol moiety. The pyridone-core and quinolinethiazol-fragment were coupled using a Stille protocol, utilizing a 2nd generation Buchwald Pd-precatalyst. Lodopyridone was obtained in a sequence of 9 linear steps (total of 16 steps) and 23% overall yield.