Studies toward Asymmetric Total Synthesis of Subincanadine F via semi-Pinacol Rearrangement

Abstract

Subincanadine F is a novel indole alkaloid possessing a bridged medium-sized heterocyclic framework, isolated in 0.002% yield as a trifluoroacetic acid salt from a Brazilian medicinal plant, Aspidosperma subincanum. The 1-azabicyclo[4,3,1]decane skeleton embedded in this alkaloid imposes a formidable synthetic challenge. Recently, we found that perhydrocyclohepta[b]indole-6,7-diol can undergo a semi-pinacol-type rearrangement into ring-contracted 1-formyl perhydro-carbazole. Moreover, the asymmetric introduction of the 6,7-diol group effectively controlled the stereochemistry of the formyl group. The scope and limitation of this potentially useful alternative to Koser’s reagent-based method were investigated, along with the application to the asymmetric total synthesis of subincanadine F.