Total Synthesis of Septedine and 7-Deoxyseptedine

Septedine (2) is a hetidine type C-20-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 alpha-methyl ketone was furnished by iridium catalyzed allylic alcohol isomerization. Sanford Csp(3)-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.