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New Bioactive Oxylipins Formed by Non-Enzymatic Free-Radical-Catalyzed Pathways: the Phytoprostanes

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Lipids

Abstract

In animals and plants, fatty acids with at least three double bonds can be oxidized to prostaglandin-like compounds via enzymatic and non-enzymatic pathways. The most common fatty acid precursor in mammals is arachidonic acid (C20:4) (AA) which can be converted through the cyclooxygenase pathway to a series of prostaglandins (PG). Non-enzymatic cyclization of arachidonate yields a series of isoprostanes (IsoP) which comprises all PG (minor compounds) as well as PG isomers that cannot be formed enzymatically. In contrast, in plants, α-linolenic acid (C18:3) (ALA) is the most common substrate for the allene oxide synthase pathway leading to the jasmonate (JA) family of lipid mediators. Non-enzymatic oxidation of linolenate leads to a series of C18-IsoPs termed dinor IsoP or phytoprostanes (PP). PP structurally resemble JA but cannot be formed enzymatically. We will give an overview of the biological activity of the different classes of PP and also discuss their analytical applications and the strategies developed so far for the total synthesis of PP, depending on the synthetic approaches according to the targets and which key steps serve to access the natural products.

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Abbreviations

AA:

Arachidonic acid

Ac:

Acetyl

ALA:

α-Linolenic acid

Bet-APE:

Betula alba L. aqueous pollen extracts

BINAL-H:

Lithium (1,1′-binaphthyl-2,2′-dioxy) aluminum dihydride

Bz:

Benzoyl

BzCl:

Benzoylchloride

CAL-B:

Candida antarctica lipase B

CH2N2 :

Diazomethane

Co2(CO)6 :

Hexacarbonyldicobalt complex

COI1:

Coronatine-insensitive1 (COI1)

CuSO4 :

Copper sulfate

DABCO:

Diazabicyclo[2.2.2]octane

DBU:

1,8-Diazabicyclo[5.4.0]undec-7-ene

DCE:

1,2-Dichloroethane

DCM:

Dichloromethane

DMF:

Dimethylformamide

DMP:

Dess-Martin Periodinane

DMSO:

Dimethylsulfoxide

dPPJ1 :

Deoxy-J1-Phytoprostane

GC:

Gas chromatography

GC–MS:

Gas chromatography–mass spectrometry

HEK cell:

Human embryonic kidney cell

HPLC:

High performance liquid Chromatography

HPLC–ESI–MS/MS:

High performance liquid chromatography–Electrospray tandem mass spectrometry

HWE:

Horner–Wadsworth–Emmons

IL:

Interleukin

IsoP:

Isoprostane

JA:

Jasmonic acid

JA-Ile:

Isoleucine–jasmonic acid conjugate

KHMDS:

Potassium hexamethyldisilazide

KOH:

Potassium hydroxide

LAH (LiAlH4):

Lithium aluminum hydride

LC:

Liquid chromatography

LiHMDS:

Lithium hexamethyldisilazide

MAPK:

Mitogen-activated protein kinases

MeAlCl2:

Methyl aluminum dichloride

mRNA:

Messenger ribonucleic acid

MS:

Mass spectrometry

NaH:

Sodium hydride

NaHMDS:

Sodium hexamethyldisilazide

NaOH:

Sodium hydroxide

NEt3 :

Triethylamine

NeuroP:

Neuroprostane

NF-κB:

Nuclear factor-kappa B

NICI:

Negative ion capture chemical ionization

NMO:

N-Methylmorpholine N-oxide

[18O3]PPE1:

Oxygen-18-labeled phytoprostane E1

OPDA:

12-Oxophytodienoic acid

PAL:

Phenylalanine ammonia lyase

Pd(OAc)2 :

Palladium II acetate

PG:

Prostaglandin

PP:

Phytoprostane

PPA1 :

Phytoprostane A1

PPAR:

Peroxisome proliferator-activated receptor

PPB1 :

Phytoprostane B1

PPD1 :

Phytoprostane D1

PPE1 :

Phytoprostane E1

PPF1 :

Phytoprostane F1

PPG1 :

Phytoprostane G1

PPh3 :

Triphenylphosphine

PPJ1 :

Phytoprostane J1

PUFA:

Polyunsaturated fatty acid

Pyr.:

Pyridine

ROS:

Reactive oxygen species

r. t.:

Room temperature

SPE:

Solid phase extraction

TBDPS:

Tert-butyldiphenylsilyl

TBS:

Tert-butyldimethylsilyl

TEA:

Triethylamine

TES:

Triethylsilyl

TFA:

Trifluoroacetic acid

TGA:

Transcription factors

THF:

Tetrahydrofuran

THP:

Tetrahydropyran-2-yl

Ts:

Tosyl

TsCl:

Tosyl chloride

UV:

Ultra-violet

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Acknowledgment

We are deeply grateful to Pr. Jean-Yves Lallemand and the ICSN for their generous financial support and a part of this work was supported by the University Montpellier I grant (BQR-2008).

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Authors and Affiliations

  1. Institut des Biomolécules Max Mousseron, IBMM, UMR 5247, CNRS, Université Montpellier I, Université Montpellier II, Faculté de Pharmacie, 15. Av. Ch. Flahault, 34093, Montpellier Cedex 05, France

    Thierry Durand, Valérie Bultel-Poncé, Alexandre Guy & Jean-Marie Galano

  2. Julius-von-Sachs-Institute for Biosciences, Pharmaceutical Biology, University of Wuerzburg, Julius-von-Sachs-Platz 2, 97082, Wuerzburg, Germany

    Susanne Berger & Martin J. Mueller

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  1. Thierry Durand
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  2. Valérie Bultel-Poncé
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  3. Alexandre Guy
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  4. Susanne Berger
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  5. Martin J. Mueller
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Correspondence to Thierry Durand.

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Durand, T., Bultel-Poncé, V., Guy, A. et al. New Bioactive Oxylipins Formed by Non-Enzymatic Free-Radical-Catalyzed Pathways: the Phytoprostanes. Lipids 44, 875–888 (2009). https://doi.org/10.1007/s11745-009-3351-1

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