Total Synthesis of Alkaloids Using Transition Metals
Dr. Hans-Joachim Knölker
Department of Chemistry
Technische Universität Dresden, Germany
Tuesday August 12, 2014
C2-361 (Reading Room)
Abstract: We described a novel synthesis of pyrroles via a three-component coupling and subsequent silver(I)-mediated oxidative cyclization of a homopropargylamine which was applied to the synthesis of the pyrrolo[2,1-a]isoquinoline alkaloid (±)-crispine A (RSC Adv. 2013, 3, 1089). The cyclization to pyrroles was developed into an efficient silver(I)-catalyzed process and used for the synthesis of pentabromopseudilin and pentachloropseudilin (Angew. Chem. Int. Ed. 2009, 48, 8042). The pentahalogenated pseudilins are a novel class of efficient inhibitors of myosin ATPase (J. Med. Chem. 2011, 54, 3675). Moreover, the halogenated pseudilins were shown to be allosteric inhibitors of the enzyme IspD, which catalyzes the non-mevalonate pathway to terpenes (Angew. Chem. Int. Ed. 2014, 53, 2235).
Carbazole alkaloids are attractive targets for organic synthesis because of their broad range of useful bioactivities (Chem. Rev. 2012, 112, 3193). We have developed two highly convergent synthetic routes to the carbazole ring system using either an iron(0)-mediated or a palladium(II)-catalyzed oxidative cyclization as key-step (Top. Curr. Chem. 2012, 309, 203; Chem. Eur. J. 2012, 18, 770).
Recent applications of our palladium(II)-catalyzed approach include the total synthesis of a range of bioactive carbazole alkaloids (Org. Biomol. Chem. 2012, 10, 7269; Chem. Eur. J. 2013, 19, 14098; Angew. Chem. Int. Ed. 2013, 52, 11073; Org. Biomol. Chem. 2014, 12, doi:10.1039/c4ob00367e).