Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product.
13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.
Napolitano
Alessandra
A
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126 Naples, Italy.
Camera
Emanuela
E
Picardo
Mauro
M
d'Ishida
Marco
M
D017302:Annexins / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis* / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation; D008084:Lipoxygenase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009573:Nitrites / Q000737:chemistry*; D009574:Nitro Compounds; D009585:Nitrogen Dioxide / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D013025:Glycine max / Q000201:enzymology; D013237:Stereoisomerism
C453800:9-nitro-11-oximino-12-oxododec-9-enoate, 4-methyl ester; D017302:Annexins; D004952:Esters; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D009573:Nitrites; D009574:Nitro Compounds; D019787:Linoleic Acid; D008084:Lipoxygenase; D009585:Nitrogen Dioxide