• DOI:10.1038/ja.2011.107
• Corpus ID: 37738279

Sargassumol, a novel antioxidant from the brown alga Sargassum micracanthum

@article{Kim2012SargassumolAN,
  title={Sargassumol, a novel antioxidant from the brown alga Sargassum micracanthum},
  author={Changmu Kim and In-Kyoung Lee and Ga Youn Cho and Kyoung Hee Oh and Young Woon Lim and Bong-Sik Yun},
  journal={The Journal of Antibiotics},
  year={2012},
  volume={65},
  pages={87-89}
}

• Changmu Kim, In-Kyoung Lee, +3 authors B. Yun
• Published 25 February 2012
• Chemistry
• The Journal of Antibiotics

Free radicals have been implicated in the pathogenesis of diseases such as ischemia, arteriosclerosis, diabetes, rheumatoid arthritis, inflammation and the initiation of cancer.1–3 There is considerable evidence that antioxidants may help prevent illnesses caused by oxidative stress due to their capacity to quench free radicals, thereby protecting cells and tissues from oxidative damage. Thus, the demand for alternative antioxidants from natural sources is gradually growing. The genus Sargassum (Sargassaceae), which belongs to the large brown algae, is distributed mainly throughout temperate Pacific coastal regions, areas of the Indian Ocean and along the Australian coast. It comprises more than 400 species. These are known to produce diverse bioactive entities including plastoquinones,4 chromanol,5 cyclopentenone6 and polysaccharides.7 S. micracanthum is found in Japan and South Korea, mainly on the south and east coasts. Extracts of S. micracanthum have been shown to exhibit antioxidant, anti-viral and selective vasodilation effects.4,5,8 As part of our ongoing effort to find natural antioxidants, we have isolated a new free-radical scavenger, designated sargassumol (1, Figure 1), from the methanolic extract of S. micracanthum. In this paper, the isolation, structure determination and free radical scavenging activity of 1 are described. Dried S. micracanthum (122 g) collected at Wando county, Jeonnam province, Korea was ground and extracted with methanol at room temperature. This methanolic extract was concentrated under reduced pressure and the aqueous resultant was consecutively partitioned with hexane, chloroform, ethyl acetate and n-butanol. The ethyl acetatesoluble portion, exhibiting potent radical scavenging activity, was concentrated under reduced pressure, subjected to Sephadex LH-20 column chromatography and eluted with 70% aqueous methanol. An antioxidant fraction was further separated by preparative reversedphase HPLC eluted with a gradient of methanol concentrations increasing to 40% in water acidified with 0.04% trifluoroacetic acid to afford compound 1 (2 mg). The molecular weight of sargassumol was determined to be 468 by FAB-mass measurements providing quasi-molecular ion peaks at m/z 469 [M+H]+ and 491 [M+Na]+ in positive mode. Its molecular formula was established to be C20H20O13 by high-resolution FAB-mass measurement (m/z 469.0952 [M+H]+, D 3.0 mmu) in combination with 1H and 13C NMR data. This molecular formula requires 11 degrees of unsaturation. The 1H NMR spectrum of sargassumol measured in DMSO (dimethyl sulfoxide)-d6 showed signals due to hydroxyl protons at d 9.26, 9.10, 7.48, 5.66 and 5.53, which are not observed in CD3OD, two aromatic methines at d 5.85, an olefinic methine at d 4.82, a methine at d 4.17, two methoxy methyl protons at d 3.73 and 3.68 and two isolated non-equivalent methylene groups at d 3.12/2.70 and 3.00/2.33. In the 13C NMR spectrum, two ketone carbonyl carbons at d 201.5 and 197.1, two ester carbonyl carbons at d 170.5 and 169.3, five sp2 quaternary carbons, three sp2 methines, three oxygenated sp3 quaternary carbons at d 81.1, 79.9 and 75.6, two methoxy methyl carbons at d 54.0 and 51.7, one methine carbon at d 52.5 and two methylene carbons at d 48.5 and 37.0 were evident. The proton-bearing carbons were established by HMQC spectrum, as shown in Table 1. In an 1H-1H COSY spectrum, the methine proton at d 4.82 (H-3) showed a cross-peak with the methine proton at d 4.17 (H-1), suggesting their allylic relationship (Figure 2). The structure of compound 1 was determined by HMBC spectrum, as shown in Figure 2. A long-range correlation of the methine proton at d 4.82 (H-3) to the oxygenated sp2 quaternary carbon at d 173.7 (C-2) and the chemical shift value of the carbonyl carbon at d 197.1 (C-4) suggested the presence of an a,b-unsaturated ketone moiety. In addition, the methine proton at d 4.82 (H-3) revealed a long-range correlation to the oxygenated sp3 quaternary carbon at d 79.9 (C-5), and the hydroxyl protons at d 5.66 and 5.53 revealed crucial HMBC correlations to the carbons at d 79.9 (C-5), 75.6 (C-9), and 48.5 (C-6) and 79.9 (C-5), 75.6 (C-9) and 52.5 (C-1), respectively, establishing a six-membered