Toward an Improved Triterpene 3-O-Glucuronidation: The Systematic Determination of the Relative Reactivities of Glucuronyl Donors and Acceptors

3-O-& beta;-Glucuronidetriterpenes are plant-derivedcompounds. Some of them have been used as herbal medicine and in pharmaceuticals,such as chikusetsu saponins and Quillaja saponins.However, the demand for these materials has remained largely a challengeowing to their natural scarcity and low-yielding purification process.Therefore, a chemical triterpene 3-O-glucuronidationwas conducted in this study to alleviate the surging demand on naturalsource. Various glucuronyl imidate donors and oleanane-type triterpeneacceptors were synthesized, and the relative reactivity values (RRV)and acceptor nucleophilic constants (Aka) were systematically measuredto study their influence on glucuronidation yield. As a result, applyingdonors in higher RRV value generally improved the production of 3-O-glucuronide triterpenes. Meanwhile, a bulky pivaloyl groupwas an ideal 2-O-protection to provide & beta;-selectivityand prevented side reactions, including orthoester formation and acyl-transferreaction. Collectively, a positive correlation was observed betweenreactive donors/acceptors and improved glucuronidation yields. Thesefindings offered insights on the influence of donors' and acceptors'reactivities on 3-O-& beta;-glucuronide triterpenessynthesis, and this knowledge would help to access saponins of interestto address future needs.

Automated summary

Chemical triterpene 3-O-glucuronidation was conducted to meet the increasing demand for natural source compounds. Reactive donors with higher reactivity values were found to improve the production of 3-O-glucuronide triterpenes. The use of a bulky pivaloyl group provided β-selectivity and prevented side reactions. These findings provide insights into the synthesis of 3-O-β-glucuronide triterpenes and are valuable for accessing desired saponins in the future.