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

4 years ago

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

Manojkumar G. Kalshetti, Narshinha P. Argade

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.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b02122

DOI: 10.1021/acs.joc.7b02122