Synfacts 2005(0): 0020-0020  
DOI: 10.1055/s-2005-865372
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of the Marine Natural Product rac-Dibromophakellstatin

Rezensent(en): Victor Snieckus, Oleg M. Demchuk
D. E. N. Jacquot, M. Zöllinger, T. Lindel*
Ludwig-Maximilians-Universität, München, Germany
Total Synthesis of the Marine Natural Product rac-Dibromophakellstatin
Angew. Chem. Int. Ed.  2005,  44:  2295-2298  
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Publikationsverlauf

Publikationsdatum:
20. Juli 2005 (online)


Significance

A synthesis of rac-dibromophakellstatin in five steps with unknown overall yield is reported. The crucial synthetic step is the unusual D-ring formation, which involves the reaction of the electron-rich enamine (B-ring) with a nitrogen electrophile. An NMR study and X-ray crystallographic analysis are reported.

Comment

Pyrrole-imidazole alkaloids constitute a family of over 100 natural products with interesting pharmacological activities, including cytotoxicity and immunosuppressive activity. The current synthesis may be compared to previous multisteps routes (up to 15 steps for enantiomerically pure compounds) (L. H. Foley, G. Büchi J. Am. Chem. Soc. 1982, 104, 1776-1777; K. J. Wiese, K. Yakushijin, D. A. Horne Tetrahedron Lett. 2002, 43, 5135-5136; K. G. Poullennec, D. Romo J. Am. Chem. Soc. 2003, 125, 6344-6345). The unusual ring D construction step may find application in other systems for imidazolidinone annelations.