Synthesis of C29- or C30-Oxidized Oleananes via Allylic Bromination and Ring Expansion: Application to the Semisynthesis of Adinandrolide.

The site-selective oxidation of C29 or C30 methyl groups in pentacyclic triterpenoids is a major synthetic challenge. Starting from betulinic acid, we developed a two-step approach involving allylic bromination followed by FeBr3/SiO2-mediated rearrangement to provide the oleanane 28,19β-lactone skeleton with moderate C30-selectivity. The utility of the method was demonstrated by the semisynthesis of the naturally occurring triterpenoid adinandrolide (2) and C20-epi-adinandrolide (11). This method provides access to highly oxidized oleanane derivatives for biological evaluation and structure-activity relationship studies.