Fatty Epoxides Research Articles

Photobiocatalytic Decarboxylation for the Synthesis of Fatty Epoxides from Renewable Fatty Acids.

Fatty epoxides are unique building blocks in organic transformations and materials production; however, their synthetic methodologies are currently not accessible from renewable fatty acids. Herein, a photoenzymatic decarboxylation of epoxy fatty acids into fatty epoxides was demonstrated using fatty acid photodecarboxylase (FAP) from Chlorella variabilis NC64A (CvFAP). Various fatty epoxides were synthesized in excellent selectivity by wild-type CvFAP. The decarboxylation reaction was also achieved with four new FAP homologues, potentially suggesting a broad availability of the biocatalysts for this challenging decarboxylation reaction. By combining CvFAP with lipase and peroxygenase, a multienzymatic cascade to transform oleic acid and its triglyceride into the corresponding fatty epoxides was established. The obtained fatty epoxides were further converted into rather unusual fatty compounds including diol, alcohol, ether, and chain-shortened carboxylic acids. The present photobiocatalytic synthesis of fatty epoxides from natural starting materials excels by its intrinsic selectivity, mild conditions, and independence of nicotinamide cofactors.

A review of fatty epoxide ring opening reactions: Chemistry, recent advances, and applications

AbstractFatty epoxides are produced from the corresponding alkenes by oxidation in the presence of peracids or other oxidants. The classic method is the Prilezhaev epoxidation in which peracids are generated by in situ oxidation of formic or acetic acids with hydrogen peroxide. Epoxidized vegetable oils and esters are used directly as biobased plasticizers and stabilizers for poly(vinyl chloride) or as important platform chemicals for the oleochemical industry. Nucleophilic attack at the oxirane moiety affords a variety of ring opened monomeric or polymeric products, which in many cases undergo further synthetic modification to yield finished products. The most common nucleophiles include water, alcohols, carboxylic acids, acid anhydrides, and amines, although numerous others can also lead to valuable functionalized fatty derivatives. This review summarizes the chemistry of fatty epoxide ring opening reactions as well as applications of the resultant products. Literature from the last 20 years will be emphasized, although older publications of particular significance will be included. Important applications include biobased lubricants as well as polyols for subsequent production of polyurethanes. In addition, ring‐opening reactions hitherto unreported on fatty oxiranes will be suggested to facilitate further advancements in the chemistry and utility of fatty epoxides. Finally, interest in fatty epoxides and their consequent products will continue to grow due to the simplicity, efficiency, and versatility of oxirane formation and ring opening as well as the continued societal transition away from petroleum to a sustainable, circular, low‐carbon, and biobased economy.

Stereostructural analysis of flexible oxidized fatty acids by VCD spectroscopy.

Oxidation of polyunsaturated fatty acids produces various oxidized lipids whose absolute configuration (AC) and conformations are difficult to analyze due to their flexibility. Through studies on hydroxy fatty acids, lipid hydroperoxides, and lipid epoxides, this work demonstrates the effectiveness of VCD spectroscopy to elucidate their AC and conformational preferences.

Surfactant properties of chemically modified chitooligosaccharides and their potential application in bitumen emulsions

Chitooligosaccharides with degree of polymerization from 5 to 15 have been modified with different lipophilic chains, from fatty epoxide to fatty acids. Their interfacial properties such as critical micellar concentrations, interfacial rheology and interfacial tension were studied to establish structure-properties relationships. Their ability to self-assemble as well as their micellar shape were assessed by light scattering (dynamic and static) and transmission electron microscopic analyses. Finally, their emulsion stabilities and rheological properties were evaluated with Turbiscan and allow the conclusion that 1% (w/w) DP10 oligomers modified with Tall oil fatty acid was able to stabilize oil in water emulsions (60/40 w/w) for at least 55 days. • Properties of chitosan-based surfactant are related to their structure. • Chitosan based surfactants present interesting interfacial properties. • Chitosan based non-ecotoxic surfactants give 55 days emulsion stabilization.

Functionalization of Chitosan Oligomers: From Aliphatic Epoxide to Cardanol-Grafted Oligomers for Oil-in-Water Emulsions.

Hydrophobically modified chitooligosaccharides (COSs) were tested for suitability as an emulsifier in cationic bituminous emulsions. COSs with polymerization degrees (DPs) of 5, 10, 15, and 20 were obtained by nitrous acid deamination. A complete study on depolymerization and precise product and side product characterization was undergone. Chemical modification of COSs was performed to achieve amphiphilic structures using three fatty epoxides with a growing chain length butyl (C4), octadecyl (C9), and hexadecyl glycidyl ether (C16)). The grafting efficiency according to reaction conditions was established. Different substitution degrees (DSs) were obtained by modulating the ratio of fatty epoxy to NH2. It was shown that after a certain DS, the oligomers thus formed were not water-soluble anymore. At the end, cardanol glycidyl ether was grafted on DP 5, 10, and 15 COSs, cardanol being a biobased compound extracted from cashew nut shell; this reaction led to a potentially fully biobased structure. Water-soluble candidates with a higher DS were used as surfactants to emulsify motor oil as a simulation of bitumen. Cardanol-chitosan-based surfactants led to direct oil-in-water emulsion (60/40 w/w) composed of particles of 15 μm average size that were stable at least for 24 h.

Biobased Aldehydes from Fatty Epoxides through Thermal Cleavage of β-Hydroxy Hydroperoxides*.

The ring-opening of epoxidized methyl oleate by aqueous H2 O2 has been studied using tungsten and molybdenum catalysts to form the corresponding fatty β-hydroxy hydroperoxides. It was found that tungstic acid and phosphotungstic acid gave the highest selectivities (92-93 %) towards the formation of the desired products, thus limiting the formation of the corresponding fatty 1,2-diols. The optimized conditions were applied to a range of fatty epoxides to give the corresponding fatty β-hydroxy hydroperoxides with 30-80 % isolated yields (8 examples). These species were fully characterized by 1 H and 13 C NMR spectroscopy and HPLC-HRMS, and their stability was studied by differential scanning calorimetry. The thermal cleavage of the β-hydroxy hydroperoxide derived from methyl oleate was studied both in batch and flow conditions. It was found that the thermal cleavage in flow conditions gave the highest selectivity towards the formation of aldehydes with limited amounts of byproducts. The aldehydes were both formed with 68 % GC yield, and nonanal and methyl 9-oxononanoate were isolated with 57 and 55 % yield, respectively. Advantageously, the overall process does not require large excess of H2 O2 and only generates water as a byproduct.

Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female Ldlr -/- mice.

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, particularly in obese and type 2 diabetic individuals. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH); and NASH can progress to cirrhosis, primary hepatocellular carcinoma (HCC) and liver failure. As such, NAFLD has emerged as a major public health concern. Herein, we used a lipidomic and transcriptomic approach to identify lipid markers associated with western diet (WD) induced NASH in female mice.MethodsFemale mice (low-density lipoprotein receptor null (Ldlr -/-) were fed a reference or WD diet for 38 and 46 weeks. Transcriptomic and lipidomic approaches, coupled with statistical analyses, were used to identify associations between major NASH markers and transcriptomic & lipidomic markers.ResultsThe WD induced all major hallmarks of NASH in female Ldlr -/- mice, including steatosis (SFA, MUFA, MUFA-containing di- and triacylglycerols), inflammation (TNFα), oxidative stress (Ncf2), and fibrosis (Col1A). The WD also increased transcripts associated with membrane remodeling (LpCat), apoptosis & autophagy (Casp1, CtsS), hedgehog (Taz) & notch signaling (Hey1), epithelial-mesenchymal transition (S1004A) and cancer (Gpc3). WD feeding, however, suppressed the expression of the hedgehog inhibitory protein (Hhip), and enzymes involved in triglyceride catabolism (Tgh/Ces3, Ces1g), as well as the hepatic abundance of C18-22 PUFA-containing phosphoglycerolipids (GpCho, GpEtn, GpSer, GpIns). WD feeding also increased hepatic cyclooxygenase (Cox1 & 2) expression and pro-inflammatory ω6 PUFA-derived oxylipins (PGE2), as well as lipid markers of oxidative stress (8-iso-PGF2α). The WD suppressed the hepatic abundance of reparative oxylipins (19, 20-DiHDPA) as well as the expression of enzymes involved in fatty epoxide metabolism (Cyp2C, Ephx).ConclusionWD-induced NASH in female Ldlr -/- mice was characterized by a massive increase in hepatic neutral and membrane lipids containing SFA and MUFA and a loss of C18-22 PUFA-containing membrane lipids. Moreover, the WD increased hepatic pro-inflammatory oxylipins and suppressed the hepatic abundance of reparative oxylipins. Such global changes in the type and abundance of hepatic lipids likely contributes to tissue remodeling and NASH severity.

Ketalization of epoxidized methyl oleate using acidic resins

BACKGROUND Fatty acid dioxolanes can be used as bioplasticizers or biolubricants, replacing petroleum-derived products. Dioxolanes can be obtained by reaction of epoxides or glycols with ketones under acidic conditions. Bronsted and Lewis acids have been reported as catalysts of the reaction. However, acidic resins have not been used so far. These heterogeneous catalysts offer high activity, reusability as well as low price. In this work, ketalization of epoxidized methyl oleate with acetone was evaluated using acidic resins (Dowex-50WX2, Amberlyst-15 and Amberlite-IR120) at low temperature (35–55 °C). RESULTS Total conversion of epoxide was obtained with Amberlyst-15, while a maximum conversion of 20% was afforded with Dowex-50WX2. However, Dowex-50WX2 was more selective to the dioxolane (max. 95% selectivity) than Amberlyst-15 (max. 76% selectivity). Amberlite IR120 afforded the lowest conversion of epoxide (max. 3%). The activation energy of the ketalization catalyzed with Amberlyst-15 was calculated as 12.53 kcal mol−1. CONCLUSION A new application of acidic resins in the ketalization of fatty epoxides at low temperatures was described. The effects of resin crosslinking and temperature were evaluated. Three kinds of products were detected: dioxolane, glycol and ketone. Several reaction pathways were proposed for ketalization over each resin. © 2016 Society of Chemical Industry

Catalytic copolymerization of methyl 9,10‐epoxystearate and cyclic anhydrides under neat conditions

The solvent‐free copolymerization of methyl 9,10‐epoxystearate 1 with different cyclic anhydrides, such as phthalic anhydride 2, succinic anhydride 3, maleic anhydride 4, or the Diels‐Alder‐adduct 5 of methyl α‐eleostearate and maleic anhydride, using a (salen)CrIIICl‐catalyst and n‐Bu4NCl as co‐catalyst is demonstrated. In this way, polyesters (Mn = 2000–10,000 g/mol) with low glass transition temperatures were formed. The reaction is characterized by sustainable aspects, for instance, the use of starting materials derived from renewable resources (>60%), low catalyst loadings, and no added solvent.Practical applicationsThe alternating ring‐opening copolymerization of epoxides such as methyl 9,10‐epoxystearate with various cyclic acid anhydrides such as phthalic anhydride and succinic anhydride, respectively, afford polyesters of narrow molecular weight distributions using a (salen)CrIIICl catalyst in the presence of n‐Bu4NCl. The pending long chain alkyl groups introduced in the polyesters by the fat derived substrates attribute amorphous properties to the polymers. Various fatty epoxides are easily available and open up the possibility for the synthesis of new highly branched polyestersPolyesters are formed by the copolymerization of methyl 9,10‐epoxystearate with different cyclic anhydrides using a (salen)CrIIICl‐catalyst in the presence of n‐Bu4NCl. The reaction is performed under neat conditions and the resulting alternating copolymers are featured by a high renewable content. In case of phthalic anhydride as co‐monomer, number average molecular weights of up to 10 kDa with narrow dispersities were obtained.

CoCuAl layered double hydroxides – efficient solid catalysts for the preparation of industrially important fatty epoxides

A scalable catalytic process for industrially important fatty epoxides is achieved by epoxidation of unsaturated fatty acid derivatives over recyclable CoCuAl-LDHs.

Epoxygenated fatty acid profile and soluble epoxide hydrolase (sEH) activity in healthy and laminitic horses

Epoxygenated fatty acid profile and soluble epoxide hydrolase (sEH) activity in healthy and laminitic horses

Synthesis of β-Amino Alcohols from Terminal Epoxy Fatty Acid Methyl Ester

Fats and oils are renewable feedstock that can be treated chemically or enzymatically to derive materials that often act as a replacement for petroleum-derived materials. Long-chain fatty epoxides can be transformed to several chemical derivatives. There has been increasing interest in using these substances as intermediates in the production of new biobased industrial materials. In the present work, renewable methyl 10,11-epoxyundecanoate were reacted with various cyclic, aliphatic, and aromatic amines in the presence of zinc(II) perchlorate hexahydrate as a Lewis acid catalyst under solvent-free conditions, to derive several new β-amino alcohols in a regioselective manner.

ORIGINAL RESEARCH: Biocatalytic production of fatty epoxides from rapeseed & tall oil derivatives: Process & environmental evaluation

Rapeseed and tall oil are important renewable feedstocks for chemicals and energy – the former, an agricultural crop, and the latter, is a by-product of the pulp and paper industry. This report presents a study on the production of fatty epoxides from rapeseed methyl ester, tall oil methyl ester, and tall oil fatty acids by a solvent-free lipase-mediated process. Fatty epoxides are useful reactive building blocks for production of lubricants, plasticizers, and surfactants. Epoxidation of the different raw materials exhibited similar reaction speeds, energy requirements, and final conversions, and the epoxide products were biodegradable and nontoxic up to high concentrations. From environmental and economic perspectives, however, the use of tall oil as raw material is preferable to rapeseed. For the chemo-enzymatic process of epoxidation to be economically feasible, improvements in biocatalyst cost and/or stability are still needed.

ADSORPTION BEHAVIOR OF EPOXIDIZED FATTY ESTERS VIA BOUNDARY LUBRICATION COEFFICIENT OF FRICTION MEASUREMENTS

The frictional behaviors of a variety of fatty alkenyl esters and their corresponding fatty epoxide esters (epoxy methyl oleate (EMO) and methyl oleate (MO), epoxy methyl linoleate (EMLO) and methyl linoleate (MLO), epoxy methyl linolenate (EMLEN) and methyl linolenate (MLEN)), epoxidized soybean oil (ESBO), and a commercial epoxidized 2-ethylhexyl transesterified soybean oil (VF) as additives in hexadecane have been examined in a boundary lubrication test regime using steel contacts. Langmuir critical additive concentrations were determined, which provide the following order of negative adsorption energies: ESBO > VF > EMO ≥ EMLO > EMLEN and MLEN ≥ MLO > MO. Thus, for the similar epoxidized materials the greater degree of epoxidation results in less negative calculated total adsorption energies; this trend is reversed for the olefinic parent systems. This ordering agrees with that obtained via a more complex unconstrained cooperative interaction adsorption model. Fits of the steady-state coefficient of friction (COF) versus concentration data indicate an inverse relation of the obtained interaction parameters (α) with the primary adsorption energies (E). These results demonstrate the complexity of the adsorption mechanism that occurs.

Specialty chemicals from vegetable oils: achievements within the Greenchem research program

AbstractIndustrial biotechnology offers promising tools for transforming renewable resources into useful products. The research program Greenchem was started in 2003 with the goal to demonstrate that environmentally benign specialty chemicals can be produced from renewables using biocatalysis. This article provides a summary of the enzymatic processes on oleochemicals successfully established so far within the program, including production of wax esters, fatty epoxides, and biosurfactants. The environmental performance of these products is also discussed and compared to the corresponding fossil oil based products, from a life cycle perspective. A general observation has been that biocatalytic reactions are more selective and energy‐efficient than the corresponding chemical processes; however, continued efforts are required for developing biocatalyst preparations with good operational stability in order to make biocatalysis an economically attractive option for the chemical industry. Furthermore, the choice of the raw material is of utmost importance in achieving the desired environmental advantages over the fossil based resources.

Hydrolysis of mono‐ and diepoxyoctadecanoates by alumina

AbstractIn this study it is shown that the epoxide derivative of oleic acid, methyl 9,10‐epoxyoctadecanoate, is readily hydrolyzed to a diol when exposed to a commercial preparation of neutral alumina. Comparison of 1H and 13C NMR spectra of the diol with those of standards showed that the product was the threo isomer. When methyl 9, 10–12,13‐diepoxyocta‐decanoate was treated with alumina, a mixture of dihydroxy‐tetrahydrofuran regioisomers, methyl 9,12‐epoxy‐10,13‐dihydroxystearate and methyl 10,13‐epoxy‐9,12‐dihydroxystearate, was obtained. These results show that alumina is an unsuitable support for epoxidation catalysts. However, alumina‐catalyzed hydrolysis of fatty epoxides is an efficient way to synthesize polyhydroxy materials, and these materials are suitable for several industrial applications.

Stereospecific Activation of Cardiac ATP-Sensitive K+Channels by Epoxyeicosatrienoic Acids: A Structural Determinant Study

The heart is richly endowed with K(ATP) channels, which function as biological sensors, regulating membrane potentials and electrical excitability in response to metabolic alterations. We recently reported that the cytochrome P450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), potently activate cardiac K(ATP) channels by reducing channel sensitivity to ATP. In the present study, we further demonstrate that 11(S),12(R)-EET activated the cardiac K(ATP) channels with an EC(50) of 39.5 nM, whereas 11(R),12(S)-EET was totally inactive. In addition, 11(S),12(R)-EET but not 11(R),12(S)-EET hyperpolarized the resting membrane potentials and shortened the duration of cardiomyocyte action potentials. By studying homologs and analogs of 11,12-EET, we also found that all four EET regioisomers are equipotent activators of the K(ATP) channels, reducing the ATP sensitivity by more than 10-fold; however, neither altered chain length, double bond number, epoxide position, nor methylation of the carboxyl group affected channel inhibitions by ATP. All the fatty epoxides studied are potent K(ATP) channel activators, but the omega-3 homolog was particularly potent, reducing ATP sensitivity 27-fold. Together, the results indicate that the presence of an epoxide group in a particular three-dimensional configuration is a critical determinant for K(ATP) channel activation, and its effect is augmented by a double bond at omega-3 position. The results also suggest that fatty epoxides are important modulators of cardiac electrical excitability.

Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels.

Diets enriched in docosahexaenoic acid, a major n-3 fatty acid in fish oil, have hypotensive properties. One mechanism that can lower blood pressure is the direct dilation of arterioles by docosahexaenoic metabolites. Vascular endothelium contains cytochrome P-450 epoxygenases that transform the n-6 fatty acid arachidonate into epoxyeicosatrienoic acids (EETs), potent dilators of coronary arterioles and activators of large-conductance calcium-activated potassium (BK(Ca)) channels. To test whether analogous activations occur for docosahexaenoate, we compared the potency of docosahexaenoate and its five cytochrome P-450 epoxygenase metabolites, epoxydocosapentaenoates (EDPs), in dilating porcine coronary arterioles (<135 microm in diameter) precontracted with endothelin. The five EDP regioisomers had dilation EC(50) values ranging from 0.5 to 24 pM (n = 5-6). In contrast, the EDP hydrolysis product 13,14-dihydroxydocosapentaenoic acid (13,14-DHDP) had an EC(50) value of 30 +/- 22 nM (n = 7), whereas docosahexaenoate only dilated vessels at > or =1.0 microM (n = 7). Using patch-clamp techniques in the inside-out configuration, we determined that the 13,14-EDP regioisomer potently activated (EC(50) value of 6.6 +/- 0.6 pM; n = 5) BK(Ca) channels in myocytes from the porcine coronary arterioles. Moreover, 13,14-EDP potently activated BK(Ca) channels in myocytes from rat coronary small arteries (150-300 microm in diameter); with an EC(50) value of 2.2 +/- 0.6 pM (n = 7), 13,14-EDP was 1000-fold more potent than EETs in activating BK(Ca) channels. We conclude that EDPs potently dilate coronary microvessels and are the most potent fatty epoxides known to activate BK(Ca) channels in coronary smooth muscle cells. Both actions may contribute to the hypotensive effects of dietary fish oils.

Epoxidation of fatty acids, fatty methyl esters, and alkenes by immobilized oat seed peroxygenase

Fatty epoxides are used as plasticizers and plastic stabilizers and are intermediates for the production of other chemical substances. The currently used industrial procedure for fatty epoxide synthesis requires a strong acid catalyst which can cause oxirane ring opening and side product formation. To find a replacement for the acid catalyst, we have been conducting research on a peroxygenase enzyme from oat ( Avena sativa) seeds and have devised a method for immobilization of this enzyme using a hydrophobic membrane support. In this study, fatty acids and fatty methyl esters commonly encountered in commercial vegetable oils were tested as substrates for immobilized peroxygenase, and the epoxide products were characterized. The epoxidation time course of linoleic acid showed two distinct phases with nearly complete conversion to monoepoxide before diepoxide was produced. The diepoxide formed from linolenic acid was found to be 9,10-15,16-diepoxy-12-octadecenoic acid, and only a trace of triepoxide was obtained. Additionally it was discovered that acyclic alkenes with internal double bonds, a cyclic alkene, and an alkene with an aromatic substituent were substrates of peroxygenase. However, alkenes with terminal unsaturation were unreactive. With every substrate examined, oat seed peroxygenase exhibited specificity for epoxidation, producing no other products, and oxirane ring opening did not occur.

Interfacial aspects of the catalysis of the synthesis of amphiphilic sucrose ethers from 1,2-epoxydodecane and 1,2-epoxydodecan-3-ol in water

The addition of sucrose on two fatty epoxides, 1,2-epoxydodecane and 1,2-epoxydodecan-3-ol, has been studied in DMSO and water. The study of the kinetics of the reaction showed that the 1,2-epoxydodecan-3-ol is more reactive for both interfacial and electronic reasons. In water, the induction time normally necessary is dramatically reduced with an immediate emulsification of the mixture which is beneficial to the interfacial formation of sucrose ethers. The comparison of the reaction in DMSO allowed to estimate the assistance of the α-hydroxyl group through intramolecular hydrogen bonding in 1,2-epoxydodecan-3-ol, revealing that both aspects are involved in the catalysis of the reaction in aqueous medium.