Total Synthesis of Septedine and 7-Deoxyseptedine

Abstract

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.