Scalable Synthesis of Quillaic Acid from Oleanolic Acid and Divergent Synthesis of Analogues Thereof †

Comprehensive Summary QS‐21 is one of the most potent saponin immunoadjuvants. However, its wide applications in subunit vaccine development are seriously restricted by its limited availability. Among the factors causing the scarcity of QS‐21, the difficult acquisition of quillaic acid (QA) on large scale is the fundamental one. Based on two steps of C–H functionalization, the Sanford C–H acetoxylation and the Yu modified Schonecker‐Baran C–H oxidation, scalable (gram‐scale) and concise (20 steps) synthesis of QA from oleanolic acid (OA) was accomplished. Moreover, based on the versatile 23,24‐Me‐diacetoxylized side product, the divergent synthesis of QA derivatives, including hederagenin analogues, oxetane‐containing OA, as well as 24‐Me‐nor‐OA, was conveniently accomplished.