Krishnagranatins A-I: New limonoids from the mangrove, Xylocarpus granatum, and NF-κB inhibitory activity

Nine new limonoids, named krishnagranatins A-I (2-5, 6a, 6b, and 7-9), were obtained from the seeds of an Indian mangrove, Xylocarpus granatum, collected at the swamp of Krishna estuary, Andhra Pradesh, together with the known one, granatumin X (1). The structures of these limonoids were established by HRESIMS, extensive NMR spectroscopic data, and single-crystal X-ray crystallography. The absolute configurations of 1, 2, and 9 were unequivocally determined by single-crystal X-ray diffraction analyses, obtained with Cu K alpha radiation. Six new limonoids, including 2-5, 6a, and 6b, belong to a small group of limonoids with a C-1-O-C-29 oxygen bridge. Compounds 2 and 5 possess a 9-OH group, whereas 3-5 contain endo-conjugated Delta(8,30) and Delta(14,15) double bonds. Compounds 6a and 6b are a pair of new limonoid C-29-epimers with the different orientation of a 29-OH group, of which the methylation leads to the chiral separation in high performance liquid chromatography (HPLC) and then affords two previously reported limonoids, sundarbanxylogranin C (6'a) and moluccensin W (6'b). Compounds 7-8 are two highly acetylated phragmalin-type limonoids, whereas 9 is a phragmalin 8,9,30-ortho ester. Compounds 7-9 exhibited inhibitory activity against the activation of NF-kappa B induced by lipopolysaccharide (LPS), but showed no obvious toxicity on RAW264.7 macrophage cells at the concentration of 10.0 mu M.