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 H₂O₂ 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.