Bing Ma, Dmitry N Litvinov, Liwen He
2009
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0
Influential Citations
30
Citations
Journal
Angewandte Chemie
Abstract
The bicyclic octapeptide celogentin C (1, Figure 1) was isolated by Kobayashi and co-workers from the seeds of Celosia argentea.[1] Other structurally similar natural products include the bicyclic peptides moroidin,[2] celogentins A–H,[3] and celogentin J,[3] as well as the monocyclic peptides celogentin K[4] and stephanotic acid.[5] Some of these compounds inhibit tubulin polymerization,[6] with 1 ranking as the most potent antimitotic agent of this natural product family. The unusual structure of 1 is derived from two cross-links between amino acid side chains. A bond between the leucine β-carbon atom and the indole C6 of tryptophan forms the left-hand ring of 1, whereas the right-hand macrocycle contains a C–N linkage between the indole C2 and the imidazole N1. The resultant heterobiaryl axis introduces the potential of atropisomer stereochemistry. The combination of useful biological activity and intriguing architecture has prompted numerous synthetic efforts targeting 1 and related compounds.[7–10] However, a total synthesis of one of the bicyclic members of the celogentin family has not yet been reported.[11] Herein, we describe our efforts which have culminated in the synthesis of celogentin C.