Seven-Membered Ring Formation in Triterpene Biosynthesis: A Key Cyclopropane Rearrangement in Ilelic Acid Biosynthesis

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Triterpenes represent a crucial class of natural compounds with diverse biological activities and structural complexity. Among the various skeletal modifications in triterpene biosynthesis, formation seven-membered rings through ring expansion reactions significantly contributes to their diversity and, consequently, functional versatility. This study elucidates detailed reaction mechanism key via cyclopropane rearrangement biosynthesis ilelic acid. Using density theory (DFT) calculations, we thoroughly investigated biosynthetic pathway acid, focusing on critical step. Our computational analysis reveals that proceeds cationic rather than radical-mediated process. Notably, found inherent instability secondary carbocation intermediate drives concerted pathway, avoiding high-energy intermediates. mechanistic understanding not only sheds light acid but also offers broader implications for comprehending similar transformations other pathways. findings contribute fundamental pave way potential biomimetic approaches synthesis complex ring-containing terpenes. Furthermore, this work underscores power methods unraveling intricate mechanisms.

Язык: Английский

Mechanistic Insights into the Nonenzymatic Biosynthesis of Artemisinin and Related Natural Products: A Quantum Chemical Study

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 13, 2025

Artemisinin (Qinghaosu) is an important antimalaria natural medicine containing a unique endoperoxide bridge in its sesquiterpene structure. The last phase of artemisinin biosynthesis involves conversion dihydroartemisinic acid (DHAA) to artemisinin, and the detailed mechanism remains unclear. Based on previous experimental studies, this work investigated possible nonenzymatic DHAA identified most chemically plausible reaction pathway using quantum chemical computations. rate-determining step acid-catalyzed oxidation enol by triplet O2, with overall free energy barrier 22.5 kcal/mol. This also gives byproducts dihydroarteannuin B dihydro-epi-arteannuin B. In addition, formation 21 products from Artemisia annua was discussed work. These results provide fundamental knowledge biosynthetic processes related products, as well references for semisynthesis structural modification studies artemisinin.

Язык: Английский