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

Manojkumar G. Kalshetti and Narshinha P. Argade^*

Division of Organic Chemistry, National Chemical Laboratory (CSIR), Pune 411 008, India

J. Org. Chem., 2017, 82 (20), pp 11126–11133

DOI: 10.1021/acs.joc.7b02122

Publication Date (Web): September 27, 2017

*E-mail: np.argade@ncl.res.in.

Cite this:J. Org. Chem. 82, 20, 11126-11133

Abstract

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.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02122.

¹H NMR, ¹³C NMR, and DEPT spectra of all compounds and HPLC plots of compound (±)-9/(−)-9 (PDF)
X-ray crystallographic data of compound 12 (CIF)
X-ray crystallographic data of compound 29 (CIF)