Total Synthesis of Thebainone A

Despite several total syntheses of opiates since the 50s, the construction of these complex alkaloids still challenges synthetic chemists nowadays. Recently the research group from Peter Metz from the TU Dresden successfully described a total synthesis of  racemic thebainone A (1) in Organic Letters. Previously thebainone A could be synthesized by Gates during the first total synthesis of morphine and also by Michael Kerr and Marcus Tius in 1992 in 24 steps.

From a retrosynthetic viewpoint thebainone A (1) the amine containing ring should be closed by nucleophilic substitution. The precursor should be derived from 2, which itself can be synthesized by cycloaddition. Finally 3 is available from isovanillin (4).

Synthesis of Cycloaddition Precursor

Completion of Total Synthesis