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

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.

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

“…A diverse range of biological activities have also been reported for spirocyclopropanes, such as anti-inflammatory, analgesic, anticancer, and cytotoxic activity [ 19 , 20 , 21 , 22 ]. The attention from compounds that incorporate this structure has not been limited to molecules of synthetic origin, but rather have focused on natural products because this functionality has been reported in several naturally occurring compounds [ 23 , 24 , 25 , 26 ]. In the case of spirocyclopropanes bound to heterocycles there are few reports of biological activity.…”

Brefeldin A from the Deep‐Sea‐Derived Fungus Fusarium sp. Targets on RIPK3 to Inhibit TNFα‐Induced Necroptosis

“…L929, HeLa, HEK293T, HT1080, HT‐29, and U937 cells from ATCC were cultured in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10 % fetal bovine serum (U937 were cultured in RIPM‐1640 plus 10 % inactive fetal bovine serum), 2 mM L‐glutamine, 100 IU penicillin, and 100 mg/mL streptomycin and were kept at 37 °C in a humidified atmosphere containing 5 % CO 2 . Cell Counting Kit‐8 (C0037, Beyotime Biotechnology) assay and Cell Titer‐Glo Luminescent Cell Viability assay (G7570, Promega) were conducted according to the manufacturer's instructions with some modifications [27,28] …”

“…Cell Counting Kit-8 (C0037, Beyotime Biotechnology) assay and Cell Titer-Glo Luminescent Cell Viability assay (G7570, Promega) were conducted according to the manufacturer's instructions with some modifications. [27,28] Immunoprecipitation and Western Blot Flag-Ripk1 knock-in L929 cells were kind gifts from Prof. Jiahuai Han of Xiamen University, China. Immunoprecipitation was performed by using M2 beads (M20018, Abmart) as described previously.…”

Michael Addition of 3-Oxo-3-phenylpropanenitrile to Linear Conjugated Enynones: Approach to Polyfunctional δ-Diketones as Precursors for Heterocycle Synthesis

“…Pyrylium derivatives allow improving mass spectrometry-based detection of peptides [20]. Cyclopropanes are applied as pesticides [21], antiproliferatives [22], drugs for the treatment of osteoporosis [23], and anti-inflammatory agents [24]. 3-Benzoylpyridines show anticonvulsant activity [25].…”