Total Synthesis and Anti-Inflammatory Bioactivity of (−)-Majusculoic Acid and Its Derivatives |
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| Authors: | Hong-Xiu Xiao Qing-Xiang Yan Zhi-Hui He Zheng-Biao Zou Qing-Qing Le Ting-Ting Chen Bing Cai Xian-Wen Yang Su-Lan Luo |
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| Affiliation: | 1.Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China;2.Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen 361005, China; (Q.-X.Y.); (Z.-H.H.); (Z.-B.Z.); (Q.-Q.L.); (T.-T.C.); (B.C.) |
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| Abstract: | The first total synthesis of marine natural product, (−)-majusculoic acid (1) and its seven analogs (9–15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner–Wadsworth–Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9–15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (−)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents. |
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| Keywords: | marine natural products, (− )-majusculoic acid, anti-inflammation, LPS, CCK-8 |
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