Current Organic Chemistry - Volume 17, Issue 8, 2013

The most remarkable difference between a chemical reaction and a lipase reaction is the fact that lipase possesses several substrate specificities, in particular, fatty acid specificity on hydrolysis, esterification, or transesterification reaction of the ester bond. Several lipases act weakly on polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and arachidonic acid. Through fatty acid specificity of lipases, a DHA-rich oil (acylglycerols) has been industrially produced from tuna oil. Lipase specificity also facilitates purification of PUFAs, conjugated linoleic acid isomers, tocopherols, and sterol esters and production of triacylglycerol that is DHA– rich at the sn- 1(3) position. Microorganism-mediated processes using Aeromonas hydrophila N- 6 are effective for production of rare unsaturated fatty acids and rare unsaturated fatty alcohols from several vegetable oils. These lipids are rarely observed in natural oils. We also demonstrate that Acinetobacter sp. N- 476- 2 effectively converts functional arachidonic acid to functional arachidonyl alcohol, which can be used as a substrate for medicine.

Plasmalogens are unique vinyl ether glycerophospholipids that serve diverse structural roles in the membranes of cells and cell organelles. Additionally, the fatty acid substitutions at sn– 2 of the glycerol backbone are dynamically removed by lipases and replaced by acyltransferases. These fatty acid storage pools provide the free arachidonic acid and docosahexaenoic acid (DHA) involved in signal transduction cascades. The biosynthesis of plasmalogens critically involves the generation of the ether lipid substitution at sn-1 of the glycerol backbone. This step only occurs in peroxisomes and is dysfunctional in genetic peroxisomal disorders and in several diseases of aging. A number of approaches have been undertaken to augment plasmalogen levels in these clinical conditions. In this review we present the current status of alkylglycerol precursors that bypass the requirement of the peroxisomal compartment.

DHA–lysophospholipids are raising considerable interest because they are recognized as being relevant to promote the biological effects of the dietary fatty acid, docosahexaenoic acid (DHA). With a view to meet the growing demand in DHA–lysophospholipids, several research works have investigated their production. DHA-lysophospholipid production can be carried out either by chemical synthesis or enzymatic synthesis using lipases or phospholipases. While synthesizing DHA–lysophospholipids, a special attention must be paid on the stability of the products. In this frame, caution is needed to prevent DHA oxidation. The reaction conditions also need to be optimized in order to minimize the phenomenon of acyl migration which could lead to random proportions of unwanted products. At last, analytical methods allowing identification and the quantification of different DHA–lysophospholipid isomers, have to be implemented in order to monitor the production.

Ether glycerophospholipids (GPLs) are a subclass of phospholipids, chemically characterized by the existence of an ether bond within the lipid molecules. Because ether GPLs are membrane structure components, they act as the wide-like resistance to membrane oxidation induced by chemical hypoxia and reactive oxygen species. The abnormal biosynthesis of ether GPLs in humans leads to the decreased supply of the critical lipids to various human cells, resulting in the alteration of the membrane lipid composition. Recent studies demonstrated that the level of docosahexaenoic acid (DHA) - containing ether molecular species of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in the Alzheimer's brain significantly decreased. On the other hand, the deficiency of DHA and plateletactivating factor in human sperm causes infertility in men. We propose that the supplementation of DHA ether molecular species of GPLs may prevent and treat brain disorders, such as Alzheimer's disease and autism, and infertility. The present review describes (1) procedures for the semi-synthesis of DHA - containing ether molecular species of PC and PE; (2) mass spectrometric methods for structurally identifying the lipids; (3) potential of DHA plasmanycholine species as lipid drugs for preventing and treating brain diseases and infertility; and (4) recommendation of marine oysters, monkfish liver and scallops based seafoods as DHA ether GPLs supplementation for the medical application.

Lysophospholipids (LPLs) are secreted physiologically by various cell types. They exhibit a broad range of biological activities, playing highly important roles in the development, activation and regulation of the immune system and are also related to cancerous cells proliferation. Consequently LPLs or their receptors have become attractive targets for developing drugs specially in the treatment of cancers. Then the development of new synthetic methods for the preparation of LPLs is a challenging problem because the elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. We will focus our attention on the chemical and enzymatic synthesis of LPLs and on the biological activity in particular of three LPLs, namely 2-lysophosphatidylcholine (2-LPC), lysophosphatidic acid (LPA) and sphingosine– 1–phosphate (S1P).

Nanomaterial drug delivery systems are promising vehicles to improve chemotherapy and decrease side effects. In the last years, there have been more reports published in prestigious journals addressing the successful application of magnetite nanoparticles in tumors treatment. The antitumor effect of magnetic fluids was studied intensely by applying an external magnetic field to retain the nanoparticles in the tumor tissue, and also to help regulating the release of loaded drugs. These features make them more competitive as a drug carrier than other nanomaterials. In addition, the MRI (magnetic resonance imaging) property of magnetic nanomaterials can enhance the monitoring of drug carriers locations. In all cases, the tumor significantly regressed in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process. Although the functionalization of nanoparticles generally refers to the addition of a polar shell to increase their solubility on the human body liquids, we have demonstrated that nanomaterials based magnetite functionalized with different types of fatty acids could exhibit antitumor properties without applying any external alternating magnetic field, when tested in vitro, on HEp-2 cells.

In light of rapid progress in biochemistry and modern bioengineering, there is a great interest in understanding how modifying the structure of naturally occurring lipids can be used to improve their nutritional and health properties. Structured lipids (SLs) or custom-made lipids can supply functional fatty acids because of their specific positioning in the glycerol structure. Health benefits of n-3 fatty acids such as docosahexaenoic acid (DHA) have been widely reported. Little information is available on the potential for health benefits of the SLs molecules that are rich in DHA and have well defined structure. This review attempts to summarize our present state of knowledge of various approaches to produce structured DHA-containing triglycerides and phospholipids as well as their applications.

Electrochemical oxidation of 4–methylesculetin has been studied in the presence of arylsulfinic acids as nucleophiles in aqueous/ acetonitrile solution mixture, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-quinone derived from oxidation of 4–methylesculetin undergoes a 1,6-Michael addition reaction with unique selectivity, converts to the corresponding new sulfone derivative of esculetin. The reaction products were derived with good yields and excellent selectivity based on electrochemical oxidation under controlled potential conditions at a carbon electrode in an undivided cell.

Volatile organic compounds (VOCs) composition of Polish honeys obtained from various geographical regions was studied. Headspace solid phase microextraction (HS-SPME) using Divinylbenzene/Carboxen/Polydimethylsiloxane-coated fibers was used in combination with comprehensive two-dimensional gas chromatography–time–of–flight mass spectrometry (GC× GC–TOFMS) because of the complexity of the samples. Acacia, linden, rapeseed, buckwheat and honeydew honeys were studied in this project.A total of 329 compounds were identified during the investigations. Positive identification of 82 compounds was achieved using analytical standards, while tentative identification of 247 compounds was based on comparison of deconvoluted mass spectra and linear temperature programmed retention indices (LTPRI) with NIST 2005 library and literature values, respectively. Many VOCs identified in Polish honey samples were commonly present in honeys from other geographical regions of Europe (e.g. Italy, Corsica). They included certain acyclic and cyclic alkanes, acyclic and cyclic alkenes, aromatic hydrocarbons, oxygenated aromatic compounds, alcohols, aldehydes, ketones, esters, ethers, nitriles, organic sulphides, phenolic compounds and terpenes. GC× GC–TOFMS profiles for the same types of honey samples were remarkably similar. Eight botanic discriminants were selected among all compounds. Their identity was confirmed by comparison with authentic standards. Furthermore, possible geographical discriminants for Polish honeys were identified, including 19 for acacia, 3 for linden, 3 for rapeseed and buckwheat and 6 for honeydew honeys.

Discotic liquid crystals, as new organic semiconductors, possess not only the ability to self-organize to a highly ordered columnar mesophase, but also possess high charged carrier mobility and solution processed characteristic. The progress of synthetic organic chemistry and new molecular designing ideas will result in improved discotic liquid crystalline semiconductors. In this report, we have investigated the CuI-Et3N catalyzed click reaction between terminal alkyne and azide, both of which contain a triphenylene moiety. Series new mono-dispersed triphenylene discotic liquid crystal oligomers containing the 1,4-disubstituted-1,2,3-triazole ring have been synthesized. Their structures have been fully characterized by FT-IR, 1H and 13C NMR spectroscopy, MALDI Mass spectrometry. The monodispersity of oligomers has been confirmed by the result of GPC. Their thermal stability and liquid crystalline properties have been studied by thermal gravimetric analysis (TGA), polarized optical microscopy (POM), differential scanning calorimetry (DSC), and X–ray diffraction (XRD). The results demonstrated that all oligomers possessed the hexagonal columnar mesophase, and were room temperature liquid crystals.

A versatile procedure for the γ -vinylogous aldol reaction of the dioxinone-derived silyl enolether, via enolate activation with an appropriate neutral Lewis base, was formulated. High levels of diastereo- and enantioselectivity using chiral 2-methylsulfinyl benzaldehyde were obtained, pointing out the dual role of the methylsulfinyl group as incorporated chiral inductor and activator of the silyloxydiene in the stereoselective vinylogous aldol reaction.