Total Synthesis and Anti-Inflammatory Bioactivity of (-)-Majusculoic Acid and Its Derivatives

  • Mar Drugs. 2021 May 21;19(6):288. doi: 10.3390/md19060288.
Hong-Xiu Xiao  1  2 ,  Qing-Xiang Yan  2 ,  Zhi-Hui He  2 ,  Zheng-Biao Zou  2 ,  Qing-Qing Le  2 ,  Ting-Ting Chen  2 ,  Bing Cai  2 ,  Xian-Wen Yang  2 ,  Su-Lan Luo  1
Affiliations
  • 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.
PMID: 34063984 DOI: 10.3390/md19060288
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.

Keywords
(−)-majusculoic acid; CCK-8; LPS; anti-inflammation; marine natural products.
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