Summary Aim Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. This aldehyde is a highly toxic molecule and should be considered as more than just a marker of lipid peroxidation. Its interaction with DNA and proteins has often been referred to as potentially mutagenic and atherogenic. This review is intended to briefly describe the physiological origin of MDA, to highlight its toxicity, describe and comment on the most recent methods of detection and discuss its occurrence and significance in pathology. Data synthesis In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed. The most recent and improved procedures for the evaluation of MDA in biological fluids are described and discussed. The evidence of the occurrence of increased MDA levels in pathology is described. Conclusions In the assessment of MDA, the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions. Moreover, no recent nutritional or medical trials report the use of one of the new and more reliable methods, some of which are undoubtedly accessible to virtually all the laboratories provided with a common HPLC or a spectrofluorimeter.

A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress

Hydrogenation is a core technology in chemical synthesis. High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The newly devised [RuCl(2)(phosphane)(2)(1,2-diamine)] complexes are excellent precatalysts for homogeneous hydrogenation of simple ketones which lack any functionality capable of interacting with the metal center. This catalyst system allows for the preferential reduction of a C=O function over a coexisting C=C linkage in a 2-propanol solution containing an alkaline base. The hydrogenation tolerates many substituents including F, Cl, Br, I, CF(3), OCH(3), OCH(2)C(6)H(5), COOCH(CH(3))(2), NO(2), NH(2), and NRCOR as well as various electron-rich and -deficient heterocycles. Furthermore, stereoselectivity is easily controlled by the electronic and steric properties (bulkiness and chirality) of the ligands as well as the reaction conditions. Diastereoselectivities observed in the catalytic hydrogenation of cyclic and acyclic ketones with the standard triphenylphosphane/ethylenediamine combination compare well with the best conventional hydride reductions. The use of appropriate chiral diphosphanes, particularly BINAP compounds, and chiral diamines results in rapid and productive asymmetric hydrogenation of a range of aromatic and heteroaromatic ketones and gives a consistently high enantioselectivity. Certain amino and alkoxy ketones can be used as substrates. Cyclic and acyclic alpha,beta-unsaturated ketones can be converted into chiral allyl alcohols of high enantiomeric purity. Hydrogenation of configurationally labile ketones allows for the dynamic kinetic discrimination of diastereomers, epimers, and enantiomers. This new method shows promise in the practical synthesis of a wide variety of chiral alcohols from achiral and chiral ketone substrates. Its versatility is manifested by the asymmetric synthesis of some biologically significant chiral compounds. The high rate and carbonyl selectivity are based on nonclassical metal-ligand bifunctional catalysis involving an 18-electron amino ruthenium hydride complex and a 16-electron amido ruthenium species.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010105%2940%3A1%3C40%3A%3AAID-ANIE40%3E3.0.CO%3B2-5

Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo‐ and Stereoselective Hydrogenation of Ketones

Chem. Pharm. Bull.(オピニオン)

Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges

Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and ...

Oxysterols: modulators of cholesterol metabolism and other processes.

Free and total malondialdehyde assessment in biological matrices by gas chromatography-mass spectrometry : what is needed for an accurate detection

Evidence for the presence of 7-hydroperoxycholest-5-en-3β-ol in oxidized human LDL

Stereoselective glucosidation of podophyllum lignans. A new simple synthesis of etoposide

Malondialdehyde (MDA), a compound derived from lipid peroxidation and from eicosanoid biosynthesis, exists in biological matrices both in the free form and bound to SH and/or NH2 groups of various biomolecules (1). Although other compounds (isoprostanes) have been proposed as more reliable indicators of oxidative damage (2), MDA is still widely used in clinical chemistry laboratories to monitor oxidative stress (3). Several methods have been developed to evaluate MDA in biological samples (1)(4), but the different analytical conditions used and the lack of a suitable internal standard have led to large discrepancies in measurements even at physiologic MDA concentrations in human plasma (5).

We (6) recently reported a “reference method” for free and total plasma MDA quantification, as the phenylpyrazole derivative, by isotope-dilution gas chromatography–mass spectrometry (ID-GC-MS) with dideuterated MDA (d2-MDA) as internal standard. This method, used for clinical MDA detection (7)(8)(9), offers the possibility of validating other proposed internal standards that differ from MDA in structure, stability, and reactivity. Unfortunately, the major limitations of d2-MDA include its difficult synthesis (10) and that it is detectable only by GC-MS, a method not always available in clinical laboratories. A compound that appears to be more suitable as an internal standard is methyl malondialdehyde (MMDA) because it is structurally close to MDA, is absent from biological matrices, is easily obtainable from a commercial compound, and is detectable by common methods such as HPLC, GC, and capillary electrophoresis.

MMDA was first evaluated as an internal standard for MDA determinations by Bull and Marnett (11), who unfortunately experienced difficulties in resolving the underivatized MDA and MMDA by HPLC. Recently, Claeson et al. (12) reported the use of MMDA as an internal standard for measurement of MDA in rat brain by capillary electrophoresis, …

Use of Methyl Malondialdehyde as an Internal Standard for Malondialdehyde Detection: Validation by Isotope-Dilution Gas Chromatography–Mass Spectrometry

The first synthesis of carminic acid (7β-D-glucopyranosyl-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid) is described. Selective C-glycosylation at the 7-position of ethyl and benzyl 3,5,8,9,10-pentamethoxy-1-methylanthracene-2-carboxylates with 2,3,4,6-tetra-O-benzyl-1-trifluoroacetyl-α-D-glucopyranose afforded intermediates which were oxidised to ethyl and benzyl 3,5,8-trimethoxy-1-methyl-9,10-dioxo-7-(2′,3′,4′,6′-tetra-O-benzyl-β-D-glucopyranosyl)-9,10-dihydroanthracene-2-carboxylate respectively. The benzyl compound was hydrogenolysed and the ethyl analogue hydrogenolysed and hydrolysed to give the same product, which was tetraacetylated and demethylated to afford 6-deoxycarminic acid tetraacetate, 3,5,8-trihydroxy-1-methyl-9,10-dioxo-7-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)-9,10-dihydroanthracene-2-carboxylic acid. The pentamethoxy intermediates were obtained from 2-chloronaphthazarin by Diels–Alder addition to 3-alkoxycarbonyl-2,4-bis(trimethylsiloxy)penta-2,4-dienes to give alkyl 6-deoxykermesates. Methylation afforded the corresponding trimethyl ethers, which by reductive methylation gave the required pentamethoxy compounds. By known steps 6-deoxycarminic acid tetraacetate was converted into the 5,8,9,10-bisquinone, acetoxylation of which gave carminic acid octaacetate. Acidic hydrolysis afforded carminic acid.

Pietro Allevi

Papers

Free and total malondialdehyde assessment in biological matrices by gas chromatography-mass spectrometry : what is needed for an accurate detection

Evidence for the presence of 7-hydroperoxycholest-5-en-3β-ol in oxidized human LDL

Stereoselective glucosidation of podophyllum lignans. A new simple synthesis of etoposide

Use of Methyl Malondialdehyde as an Internal Standard for Malondialdehyde Detection: Validation by Isotope-Dilution Gas Chromatography–Mass Spectrometry

Synthesis of carminic acid, the colourant principle of cochineal