Abstract
Determination of the absolute configrations for natural products is one of the most important and challenging tasks, especially when the molecules display high conformational flexibility. In this paper, eight new prenylxanthones, aspergixanthones A-H (1–8), and one known analogue (9), were isolated from the marine-derived fungus Aspergillus sp. ZA-01. The absolute configurations of C-14 and C-15 in 1–8 were difficult to be assigned due to the high conformational flexibility of the chains. To solve this problem, the experimental ECD, ORD, and VCD spectra of 1 were combined for analysis with the corresponding theoretical predictions for its different diastereomers. This study suggested that a concerted application of more than one chiroptical methods could be used as a preferable approach for the stereochemical characterizations of flexible molecules. Compounds 1–9 were evaluated for their cytotoxic and antibacterial activities. Among them, 6 showed cytotoxicity against the A-549 cell line with the IC50 value of 1.1 μM, and 7 exhibited antibacterial activity against Micrococcus lysodeikticus with the MIC value of 0.78 μg/mL.
Highlights
This work demonstrated that using multiple chiroptical methods in combination with DFT calculations allowed one to determine absolute configurations with high confidence for chiral natural products, which possessed rotatable bonds
Three chiroptical methods, including electronic circular dichroism (ECD), optical rotatory dispersion (ORD) and vibrational circular dichroism (VCD), combined with quantum theory calculation were carried out to elucidate the absolute configuration of the prenylxanthone 1, which was difficult to be determined by single method due to high flexibility of the molecule
Optical rotations were obtained on an Optical Activity AA-55 series polarimeter
Summary
Aspergixanthone A (1) was isolated as a yellow powder, with the molecular formula of C28H32O9 (12 degrees of unsaturation) established by positive HRESIMS (m/z 535.1935 [M + Na]+, calcd. for 535.1939). Compounds 5 and 6 were prenylxanthone analogues by the comparison of the strikingly similar NMR data of 5 and 6 (Tables 2 and 3) with those of 1 and 2, with the appearance of the additional acetoxy groups in 5 and 6. This work demonstrated that using multiple chiroptical methods in combination with DFT calculations allowed one to determine absolute configurations with high confidence for chiral natural products, which possessed rotatable bonds. Three chiroptical methods, including ECD, ORD and VCD, combined with quantum theory calculation were carried out to elucidate the absolute configuration of the prenylxanthone 1, which was difficult to be determined by single method due to high flexibility of the molecule. Potent biological activities of these prenylxanthones (1–9) may encourage further investigations on this cluster of metabolites for drug discovery
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