American Chemical Society
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Toward an Improved Triterpene 3‑O‑Glucuronidation: The Systematic Determination of the Relative Reactivities of Glucuronyl Donors and Acceptors

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journal contribution
posted on 2023-07-06, 14:37 authored by Yen-Hsun Lai, Yu-Ting Chou, You-Yu Lin, Yi-Chi Wang, Jing-Xiu Cao, Pi-Hui Liang
3-O-β-Glucuronide triterpenes are plant-derived compounds. 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 challenge owing to their natural scarcity and low-yielding purification process. Therefore, a chemical triterpene 3-O-glucuronidation was conducted in this study to alleviate the surging demand on natural source. Various glucuronyl imidate donors and oleanane-type triterpene acceptors were synthesized, and the relative reactivity values (RRV) and acceptor nucleophilic constants (Aka) were systematically measured to study their influence on glucuronidation yield. As a result, applying donors in higher RRV value generally improved the production of 3-O-glucuronide triterpenes. Meanwhile, a bulky pivaloyl group was an ideal 2-O-protection to provide β-selectivity and prevented side reactions, including orthoester formation and acyl-transfer reaction. Collectively, a positive correlation was observed between reactive donors/acceptors and improved glucuronidation yields. These findings offered insights on the influence of donors’ and acceptors’ reactivities on 3-O-β-glucuronide triterpenes synthesis, and this knowledge would help to access saponins of interest to address future needs.