title: Total synthesis of dimeric pyrrole-imidazole alkaloids: sceptrin, ageliferin, nagelamide e, oxysceptrin, nakamuric acid, and the axinellamine carbon skeleton.
abstract: The dimeric pyrrole imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, high nitrogen content, and exciting bioactivities. This full account traces the evolution of a strategy that culminated in the first total syntheses of several members of this family, including sceptrin, ageliferin, nagelamide E, nakamuric acid (and its methyl ester), and oxysceptrin. Details on the fascinating conversion of sceptrin to ageliferin, which has been used to produce gram quantities of this sensitive natural product, are provided. In addition, the first enantioselective total synthesis of sceptrin and ageliferin are reported by programming the fragmentation of an oxaquadricyclane. A hallmark of our approach to this family of alkaloids is the minimal use of protecting groups despite the presence of 10 nitrogen atoms in the target compounds. Thus, the fundamental chemistry of the 2-aminoimidazole heterocycle was explored without masking its innate reactivity. Insights gained during these explorations led to total syntheses of oxysceptrin and nakamuric acid and a successful construction of the carbon skeleton of axinellamine.
authors: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Daniel P
authors: DP
authors: O'Malley
authors: Ke
authors: K
authors: Li
authors: Michael
authors: M
authors: Maue
authors: Alexandros L
authors: AL
authors: Zografos
authors: Phil S
authors: PS
authors: Baran
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D019281:Dimerization; D004952:Esters / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D000470:Alkaloids; D004952:Esters; D007093:Imidazoles; D008698:Mesylates; D011758:Pyrroles; C514118:ageliferin; C520388:axinellamine; C520386:nagelamide E; C520387:nakamuric acid; C068123:oxysceptrin; D002244:Carbon; C077210:sceptrin