First Total Synthesis of (±)-Melinonine-E and (±)-Strychnoxanthine Using a Radical Cyclization Process as the Core Ring-Forming Step

Abstract

The first total synthesis of (±)-melinonine-E and (±)-strychnoxanthine is described. The key common step for the synthesis of both alkaloids is the elaboration of the 2-azabicyclo[3.3.1]nonane nucleus (D and E rings) by a radical carbocyclization, using an α-carbamoyldichloromethyl radical as a donor. The closure of the C ring by a Bischler−Napieralski cyclization, followed by an epimerization process to gain the axial nitrile 20, and appropriate reduction transformations afforded pentacyclic alcohol 23. This alcohol was converted into either (±)-melinonine-E (1) or (±)-strychnoxanthine (2) by means of a palladium black dehydrogenation of the C ring or a SeO2 oxidation of the corresponding acetate 25, respectively.