First Synthesis of Cytotoxic 8,9-Secokaurene Diterpenoids. An Enantioselective Route to (−)-O-Methylshikoccin and (+)-O-Methylepoxyshikoccin

A practical route for the total synthesis of 8,9-secokaurene diterpenes is described. The central step is the [3.3]sigmatropic rearrangement of spirocyclic intermediates such as 35, 40, and 41 . All three compounds must necessarily respond identically to properly install the absolute configuration of the bridgehead methine carbon. The total synthesis of (−)- O -methylshikoccin ( 2b ) was realized in 8% overall yield from the Wieland−Miescher ketone 9 . Its naturally occurring epoxide 47 was prepared with comparable efficiency. The preparative route developed herein should provide a general entry into this important class of diterpenoids.