Total Synthesis of the Spirocyclic Oxindole Alkaloids Corynoxine, Corynoxine B, Corynoxeine, and Rhynchophylline

Racemic total syntheses of four spirocyclic oxindole alkaloids are reported. The general starting material was an N-2-butenylated 2-hydroxytryptamine, which underwent a base-mediated Mannich spirocyclisation with a functionalised aldehyde to generate the C-ring. The second key step was a Pd-catalysed cyclisation of an alpha-keto ester enolate (in the original aldehyde) onto an allylic carbonate (in the N-substituent) to form the D-ring. The stereoselectivities of the key steps were moderate, but the isomers were readily purified, so that the natural products could be conveniently prepared, three of them for the first time.