Total Synthesis of Septedine and 7‑Deoxyseptedine

Septedine (2) is a hetidine type C20-diterpenoid
alkaloid bearing an oxygenated heptacyclic scaffold. We have accomplished
the first and asymmetric total synthesis of 2 and its
7-deoxy analogue 3. A functionalized tricyclic intermediate
was prepared with excellent enantiopurity by using Carreira polyene
cyclization. An unusual anionic Diels–Alder reaction was responsible
for the construction of the bicyclo[2.2.2]­octane. The α-methyl
ketone was furnished by iridium-catalyzed allylic alcohol isomerization.
Sanford Csp3–H oxidation was exploited to install
the secondary hydroxy group of 2. The oxazolidinopiperidine
was assembled by selective reductive amination and spontaneous N,O-ketalization at a final stage.