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

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 stereochemi...

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Bibliographic Details
Published in:Marine drugs 2021-05, Vol.19 (6), p.288
Main Authors: Xiao, Hong-Xiu, Yan, Qing-Xiang, He, Zhi-Hui, Zou, Zheng-Biao, Le, Qing-Qing, Chen, Ting-Ting, Cai, Bing, Yang, Xian-Wen, Luo, Su-Lan
Format: Article
Language:English
Subjects:
(−)-majusculoic acid
Analogs
anti-inflammation
Anti-inflammatory agents
Biocompatibility
Biological activity
Carboxylic acids
CCK-8
Cyclopropane
Cytokines
Cytotoxicity
Fatty acids
Inflammation
Kinases
Lipopolysaccharides
LPS
Macrophages
marine natural products
Natural products
Nitric oxide
NMR
Nuclear magnetic resonance
Reagents
Synthesis
Toxicity
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Summary: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.
ISSN:1660-3397
1660-3397
DOI:10.3390/md19060288