Application of Organic Synthesis to Study Bioactive Natural Products from Artemisia annua: Dihydroartemisinic Acid to Artemisinin Mechanism and Arteannuin B Mode of Action

Date

2024

Authors

Varela, Kaitlyn

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Abstract

Artemisia annua (A. annua, qing hao, sweet wormwood) is a leafy plant that is traditionally used as an herbal medicine. A. annua is harvested to extract the anti-malarial compound, artemisinin, as well as other bioactive natural products from its leaves. Due to its wide range of applicability to human health, research surrounding the bioactive natural products produced by A. annua are ongoing to best replicate and utilize medicinal compounds isolated from the plant. Artemisinin, arteannuin B, artemisinic acid, and dihydroartemisinic acid are among several major sesquiterpenoids within the plant that are known for their therapeutic value. The biosynthesis of artemisinin within A. annua is highly controversial, with scientific evidence supporting a spontaneous, non-enzymatic process, as well as an enzymatic process. This research aims to investigate the spontaneous, non-enzymatic conversion of dihydroartemisinic acid to artemisinin using mechanistic studies. Deuterated isotopologues of dihydroartemisinic acid were synthesized to develop a thorough mechanistic understanding using mass spectrometry and calculated kinetic isotope effects. The role of the monoalkene in dihydroartemisinic acid was studied to determine whether a desaturated dihydroartemisinic acid analog would undergo endoperoxide formation. Finally, the natural product arteannuin B (isolated from A. annua) was used in adduction and inhibition studies on two cysteine proteases to determine its viability as a cysteine protease inhibitor and its mode of action. Through these experiments, this research aims to apply organic synthesis to study bioactive natural products from Artemisia annua.

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Keywords

Arteannuin B, Artemisia annua, Artemisinin, Natural Products, Organic Synthesis

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Department

Chemistry