Challenging the Boundaries of Synthesis PIAs

Baran also postulated that these simpler dimeric PIAs could be precursors to the more advanced tetracyclic and hexacyclic family members. Key to this hypothesis was the common putative intermediate pre-axinellamine (139), which hypothetically could be produced from both the rearrangement of sceptrin (66) or ageliferin (132) (Schane 13.22) [114]. Oxidative ring expansion (sceptrin) or contraction (ageliferin) induced by either electrophilic oxygen or chlorine, respectively, would lead to formation of the highly functionalized cyclopentane core (137) of this hypothetical compound. Eurther oxidation of the aminoimidazole would then yield pre-axinellamine (139). 

Baran suggested that through differing hydration states, pre-axinellamine (139) could lead to multiple members of 

SCHEME 13.21 Conversion of sceptrin to ageliferin by rupture of the cyclobutane. 

SCHEME 13 2 Baran s hypotheses for the generation of pie-axineUamine from both sceptrin and ageliferin. 

SCHEME 13.23 Proposed conversion of pre-axinellamine to other pyrrole-imidazole alkaloids. 

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