Total Synthesis of (±)/(+)-Subincanadine E and Determination of Absolute Configuration

A facile
synthesis of (±)-subincanadine E was described from
tryptamine-based maleimide. 1,2-Addition of Grignard reagent to maleimide,
internal activation of formed lactamol for in situ 1,4-addition of
Grignard reagent, and associated position-specific allylic rearrangement
in diastereoselective Pictet–Spengler cyclization were the
key steps. Enantioselective first total synthesis of naturally occurring
cytotoxic (+)-subincanadine E was also accomplished from (S)-acetoxysuccinimide via an unusual syn-addition of cuprate to the α,β-unsaturated lactam. Sinister absolute configuration was assigned to (+)-subincanadine
E on the basis of total synthesis. (S)-Acetoxy group
in the succinimide precursor was initially employed to impart regio-
and stereoselectivity and then as a suitable leaving group to generate
the desired conjugated lactam.