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

Abstract

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.