Total Synthesis of (+)-Arborisidine

The first total synthesis
of arborisidine, a unique Kopsia indole alkaloid
possessing a fully substituted cyclohexanone ring
system with two quaternary carbons, has been achieved in seven steps
in racemic format from tryptamine and in nine steps in asymmetric
format from d-tryptophan methyl ester. Key elements of the
design include a carefully orchestrated decyanation protocol to finalize
the asymmetric formation of an aza-quaternary center
that is challenging to access in optically active format via direct
Pictet–Spengler cyclizations with tryptamine, a metal-promoted
6-endo-dig cyclization of an enyne to establish the
second core quaternary center, and regiospecific functionalizations
of the resultant complex diene to finalize the target structure. The
distinct and efficient nature of the developed solution is highlighted
by several unsuccessful approaches and unexpected rearrangements.