Gram-scale synthesis of alstoscholarinoid B via a bio-inspired strategy

Alstoscholarinoid A is a novel rearranged triterpene with an unprecedented 6/6/5/6/6/6 framework and an additional unique C28 -> C11-olide F-ring, and displays antihyperuricemic bioactivity. Herein, we report a bio-inspired synthesis of alstoscholarinoid B in a stepwise manner, which is amenable to gram-scale synthesis. The synthesis involved the Chugaev elimination as a key step to realize the migration of the Delta(11,12)-double bond of oleanolic acid, and also featured a sequential LiHMDS-mediated intramolecular aldol condensation/lactonization to establish the polycyclic ring system. Additionally, a tandem deprotection/aldol condensation/lactonization process under the influence of LiI/2,4,6-collidine for forging the polycyclic scaffold was also serendipitously discovered. Mechanistic studies indicated that lithium carboxylate might function as an inner base for the chemoselective alpha-deprotonation of the C12-aldehyde.

Automated summary

In this study, a bio-inspired synthesis of alstoscholarinoid B was reported, which is amenable to gram-scale synthesis. The synthesis involved a Chugaev elimination step, LiHMDS-mediated intramolecular aldol condensation/lactonization, and a serendipitously discovered tandem deprotection/aldol condensation/lactonization process under the influence of LiI/2,4,6-collidine.