Asymmetric Total Synthesis of Arcutinidine, Arcutinine, and Arcutine

We have accomplished the asymmetric
total synthesis of arcutinidine,
arcutinine, and arcutine, three arcutine-type C20-diterpenoid alkaloids.
A pentacyclic intermediate was rapidly assembled by using two Diels–Alder
reactions. We developed a cascade sequence of Prins cyclization and
Wagner–Meerwein rearrangement to construct the core of arcutinidine,
which was then elaborated into an oxygenated pentacycle through a
scalable route. Chemoselective reductive amination followed by spontaneous
imine formation furnished the pyrroline motif in the final stage.
We clarified the S configuration of the α-carbon
of the acyl group within arcutine through chemical synthesis and crystallographic
analysis.