Artemisitene formation during UVA ‐assisted Fenton oxidation of arteannuin B

Artemisitene (ARE) is a highly oxidized sesquiterpene isolated from Artemisia annua L., differing structurally from the antimalarial drug artemisinin (ART) only by the presence of a double bond between C11 and C13. ART is derived from the photooxidation of dihydroartemisinic acid, while the formation of ARE is unknown. In this study, arteannuin B (ART‐B) was oxidized using a UVA‐assisted Fenton reaction under optimized conditions: methanol/water = 1:3 (v/v) and H 2 O 2 concentration = 100 mM, and ARE as well as other ART‐B derivatives, including a novel compound 13‐homo‐artemanin A, were detected by gas chromatography–mass spectrometry (GC–MS) and high‐performance liquid chromatography (HPLC), respectively. Furthermore, the structure of the new compound was identified by HRMS, 1D NMR, and 2D NMR spectra. Quantitative analysis revealed that ART‐B consumption reached 93.3%, accompanied by a formation yield of ARE at 4.8%. These results indicate that ART‐B is highly likely the precursor of ARE in a UVA‐dependent manner, which provides preliminary evidence for identifying the precursor of ARE/ART and expands the application of photo‐Fenton systems in oxidation and structural diversification of natural sesquiterpenes.