Synthesis of a novel naphthalenone endoperoxide and structural elucidation by nuclear magnetic resonance spectroscopy and theoretical calculation

Abstract

Sesquiterpene lactones are found in plants of Asteraceae family, and endoperoxides are known for their antimalarial activity. Structural elucidation is a relevant aspect; however, it is not uncommon to find incorrect or incomplete structural assignments in the literature. Calculations based in quantum mechanics are frequently used to compute 1 H and 13 C NMR chemical shifts, and after comparing with the experimental data, the correct structure is established from diverse candidates. Targeting the synthesis of bioactive compounds, we envisaged the synthesis of a novel endoperoxide from the natural sesquiterpene lactone α-santonin (2). Photochemical transformation of α-santonin (2) to mazdasantonin (4) followed by photooxidation catalyzed by rose bengal afforded the novel endoperoxide 5. This new endoperoxide contains five stereogenic centers and is analogous to the antimalarial agent artemisinin (1). The relative configuration of the stereogenic centers of the endoperoxide were established by nuclear magnetic resonance (NMR) analyses and confirmed by theoretical calculations.

Analytical and Structural Tools of Lipid Hydroperoxides: Present State and Future Perspectives

“…Quantum chemical calculations of NMR parameters have also been extensively used for the precise determination of diastereomerism of natural products with multiple asymmetric centers [ 138 , 141 , 142 , 143 , 158 , 159 , 160 , 161 ]. On the contrary, in the field of lipid hydroperoxides, only three papers have so far been reported [ 138 , 141 , 156 ].…”

Deciphering molecular structures: NMR spectroscopy and quantum mechanical insights of halogenated 4H‐Chromenediones

“…30,49 This approach was first described by Bifulco, 29 and has been successfully applied in several situations in our research group. 22,25,31,36,38,[50][51][52][53][54][55][56][57][58] 2 | RESULTS AND DISCUSSION 2.1 | Synthesis and mechanism α-santonin (1) is known for having a versatile photochemical reactivity that is highly dependent on reaction conditions, such as the polarity and acidity of the solvent employed, suitable wavelength irradiation, and temperature. 46,59,60 Photosantonic acids (2), the starting material used in the synthesis of halogenated 4H-chromenediones, were obtained by irradiation of the sesquiterpene lactone α-santonin (1) in the ultraviolet region using a mixture of H 2 O/acetic acid 1:1 as solvent (Scheme 1).…”