Total synthesis of indole alkaloid (±)-subincanadine F via SmI ₂-mediated ring opening and bridge-forming Mannich reaction

(Chemical Equation Presented) The first total synthesis of (±)-subincanadine F, a bioactive indole alkaloid structurally featuring a 1-azabicyclo[4.3.1]-decane unit, has been realized from 1-(para-methoxybenzyl)- tryptamine in six steps. The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by a SmI₂-mediated ring opening followed by an acid-mediated Mannich reaction. In addition, the tetracyclic ketoester 6, a key intermediate potentially useful for synthesizing structurally related indole alkaloids as well, was obtained in one step from α,β-diketoester 5.