Controlled Conversion of C3-Ketoxime Triterpenoids to A-Lactam or A-seco-Nitrile Scaffolds

In this work, we report the investigation of several Beckmann rearrangement conditions to selectively produce seven-membered A-lactam and A-seco-nitrile derivatives from triterpenoids. Using C3-oxime-C28-acetate betulin as a model substrate, the presence of zinc chloride in the reaction gave the best yields of either the amide or the ring-opened nitrile products but the preference between the Beckmann rearrangement versus fragmentation was dictated by the solvent used. The scope of the reaction was extended to other triterpenoids such as lupeol, betulinic acid, and oleanolic acid. Convenient and safe, the reported method was performed on scales up to 20 g, employs cost-effective reagents, and allows the rapid generation of attractive triterpenoid scaffolds and potentially bioactive molecules.