Synthesis of ent-kaurane and beyerane diterpenoids by controlled fragmentations of overbred intermediates

Abstract

In the first part of a two-phase pursuit of highly oxidized members of the ent-kaurane and beyerane diterpenoid families, steviol was identified as the ideal cyclase phase terminus. Accordingly, a synthesis of steviol has been developed. This synthesis features a polyene cyclization precursor designed to directly yield oxidation on the axial C₁₉ methyl group. Construction of the necessary [3.2.1]bicyclic system found in the ent-kaurane skeleton was realized with two overbred intermediates. The resulting [3.2.1]bicyclic system undergoes Wagner–Meerwein rearrangement to yield the beyerane skeleton of isosteviol.

Keywords: beyerane; diterpenes; ent-kaurane; overbred intermediates; total synthesis.