Synthesis and biological activity of hydroxylated derivatives of linoleic acid and conjugated linoleic acids

School of Biotechnology, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
Chemistry and Physics of Lipids (Impact Factor: 2.59). 03/2009; 158(1):39-45. DOI: 10.1016/j.chemphyslip.2008.12.004
Source: PubMed

ABSTRACT Allylic hydroxylated derivatives of the C18 unsaturated fatty acids were prepared from linoleic acid (LA) and conjugated linoleic acids (CLAs). The reaction of LA methyl ester with selenium dioxide (SeO(2)) gave mono-hydroxylated derivatives, 13-hydroxy-9Z,11E-octadecadienoic acid, 13-hydroxy-9E,11E-octadecadienoic acid, 9-hydroxy-10E,12Z-octadecadienoic acid and 9-hydroxy-10E,12E-octadecadienoic acid methyl esters. In contrast, the reaction of CLA methyl ester with SeO(2) gave di-hydroxylated derivatives as novel products including, erythro-12,13-dihydroxy-10E-octadecenoic acid, erythro-11,12-dihydroxy-9E-octadecenoic acid, erythro-10,11-dihydroxy-12E-octadecenoic acid and erythro-9,10-dihydroxy-11E-octadecenoic acid methyl esters. These products were purified by normal-phase short column vacuum chromatography followed by high-performance liquid chromatography (HPLC). Their chemical structures were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). The allylic hydroxylated derivatives of LA and CLA exhibited moderate in vitro cytotoxicity against a panel of human cancer cell lines including chronic myelogenous leukemia K562, myeloma RPMI8226, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cells (IC(50) 10-75 microM). The allylic hydroxylated derivatives of LA and CLA also showed toxicity to brine shrimp with LD(50) values in the range of 2.30-13.8 microM. However these compounds showed insignificant toxicity to honeybee at doses up to 100 microg/bee.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Methyl (2E,4R)-4-hydroxydec-2-enoate, methyl (2E,4S)-4-hydroxydec-2-enoate, and ethyl (±)-(2E)-4-hydroxy[4-2H]dec-2-enoate were chemically synthesized and incubated in the yeast Saccharomyces cerevisiae. Initial C-chain elongation of these substrates to C12 and, to a lesser extent, C14 fatty acids was observed, followed by γ-decanolactone formation. Metabolic conversion of methyl (2E,4R)-4-hydroxydec-2-enoate and methyl (2E,4S)-4-hydroxydec-2-enoate both led to (4R)-γ-decanolactone with >99% ee and 80% ee, respectively. Biotransformation of ethyl (±)-(2E)-4-hydroxy(4-2H)dec-2-enoate yielded (4R)-γ-[2H]decanolactone with 61% of the 2H label maintained and in 90% ee indicating a stereoinversion pathway. Electron-impact mass spectrometry analysis (Fig. 4) of 4-hydroxydecanoic acid indicated a partial C(4)→C(2) 2H shift. The formation of erythro-3,4-dihydroxydecanoic acid and erythro-3-hydroxy-γ-decanolactone from methyl (2E,4S)-4-hydroxydec-2-enoate supports a net inversion to (4R)-γ-decanolactone via 4-oxodecanoic acid. As postulated in a previous work, (2E,4S)-4-hydroxydec-2-enoic acid was shown to be a key intermediate during (4R)-γ-decanolactone formation via degradation of (3S,4S)-dihydroxy fatty acids and precursors by Saccharomyces cerevisiae.
    Helvetica Chimica Acta 12/2011; 94(12). DOI:10.1002/hlca.201100280 · 1.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bioassay-guided fractionation of Alternanthera brasiliana stem extracts resulted in the isolation of an antibiotically active fraction. Five human pathogenic bacteria were used to guide the fractionation process for the isolation of antimicrobial compounds. Finally, 17 linoleate oxylipins were identified by LC-MS/MS and NMR spectroscopy. Five of the isolated compounds present in A. brasiliana tissues were also detected to be synthesized by endophytic bacteria of the genus Bacillus that were isolated from A. brasiliana. It is speculated that the antibiotic oxylipins from A. brasiliana might derive from bacteria and be involved in an ecological relationship between this plant and its endophytes. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Phytochemistry 11/2014; DOI:10.1016/j.phytochem.2014.11.005 · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two new fatty alcohols named as (7S,8R,11S)-nonacosanetriol (1) and (10R,12R,15S)-nonacosanetriol (2), along with eight known compounds including ginkgolic acid (3), hydroginkgolic acid (4), sciadopitysin (5), ginkgetin (6), isoginkgetin (7), ginkgolide A (8), ginkgolide B (9) and ginkgolide C (10) have been isolated from the petroleum ether extract of Ginkgo biloba sarcotesta. Their structures were elucidated by means of chemical and extensive spectroscopic analysis. The absolute stereochemistry of compounds 1 and 2 was elucidated on the spectroscopic analysis of the R- and S-MTPA esters. Compounds 1 and 2 exhibited slight activity of antithrombin and moderate activity of antiplatelet aggregation in vitro. This was the first report regarding the anticoagulative activities of biflavonoids in G. biloba, and isoginkgetin (7) showed significant antithrombin and antiplatelet aggregation activity.
    Chemistry and Physics of Lipids 09/2012; 165(7):731-736. DOI:10.1016/j.chemphyslip.2012.08.003 · 2.59 Impact Factor