- Improved enzymatic synthesis route for highly purified diacid 1,3-diacylglycerols
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The nutritional benefits and biological functions of diacylglycerols (DAGs) have attracted much attention regarding their synthesis. In this study, we improved the synthesis of diacid 1,3-DAGs by the enzymatic transesterification of 1-monoolein with a fatty acid vinyl ester as an acyl donor. First, 1-monoolein was prepared in 95% ethanol with Amberlyst resin as a catalyst by the cleavage of 1,2-acetonide-3-oleoylglycerol, which had been synthesized by enzymatic esterification of 1,2-acetonide glycerol with oleic acid. Second, purified 1-monoolein was reacted with vinyl palmitate in the presence of a lipase to obtain 1-oleoyl-3-palmitoylglycerol. Subsequently, the reaction conditions for the synthesis of diacid 1,3-DAGs were evaluated. Under the selected conditions, the crude mixture contained 90.6% pure 1-oleoyl-3-palmitoylglycerol. After purification by two-step crystallization, pure 1-oleoyl-3-palmitoylglycerol was obtained with a yield of 83.6%. The main innovations were the use of enzymatic transesterification to obtain highly purified diacid 1,3-DAGs instead of using chemical synthesis and the use of an irreversible reaction with a fatty acid vinyl ester as acyl donor rather than reversible reactions.
- Wang, Xingguo,Wang, Xiaosan,Xiao, Jianhui,Zou, Wanzhen,Han, Zhengyang,Jin, Qingzhe
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- An isozyme of earthworm serine proteases acts on hydrolysis of triacylglycerol
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An enzyme catalyzing the hydrolysis of triacylglycerol was purified from an earthworm. The N-terminal amino acid sequence and the catalytic function of the purified enzyme were identical to those of Isozyme C, an isozyme of the earthworm-serine proteases. No other lipase proteins were found in the earthworm cells. The isozyme might act on the hydrolysis of triacylglycerol as well as the protein decomposition.
- Nakajima, Nobuyoshi,Sugimoto, Manabu,Tsuboi, Sadao,Tsuji, Hideaki,Ishihara, Kohji
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- MgO-based catalysts for monoglyceride synthesis from methyl oleate and glycerol: Effect of Li promotion
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The synthesis of monoglycerides (glyceryl monooleates) by heterogeneously catalyzed glycerolysis of an unsaturated fatty acid methyl ester (methyl oleate) was studied on MgO and Li-promoted MgO catalysts. Several MgO-based catalysts with different Li loadings were prepared by incipient wetness impregnation and characterized by XRD, N2 physisorption, and FTIR and TPD of CO 2 among other techniques. Promotion of MgO with lithium, a basic promoter, affected the textural and structural properties of the resulting oxides so that more crystalline MgO phases with decreased surface area were obtained at increasing Li contents. Furthermore, the addition of Li generated new strong base sites because of formation of dispersed surface Li2O species, and thereby increased the total base site density of parent MgO. Li-containing MgO catalysts efficiently promoted the glycerolysis reaction, achieving high monoglyceride yields (70-73%) at 493 K. The initial monoglyceride formation rate increased linearly with the Li content on the sample following the enhanced overall catalyst base strength. Although conversions at the end of the run were ≈100% for all the catalysts, the monoglyceride selectivity slightly decreased with the Li loading, probably as a consequence of the less surface affinity for glycerol adsorption that facilitates competing monoglyceride re-adsorption and transformation to diglycerides by consecutive glycerolysis or disproportionation reactions.
- Ferretti,Apesteguía,Di Cosimo
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- Study on acyl migration kinetics of partial glycerides: Dependence on temperature and water activity
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Acyl migration phenomenon was often observed during 1,3-positional specificity lipase-catalyzed reactions from triglycerides and partial glycerides, including acyl migration of 1,2-diglyceride (1,2-DG) to 1,3-diglyceride (1,3-DG) and 2-monoglyceride (2-MG) to 1-monoglyceride (1-MG). However, the acyl migration mechanism and kinetics were seldom studied despite of numerous researches on process optimization of 1,3-positional specificity lipase-catalyzed reaction. In this paper, the influence of related factors on acyl migration process as well as their influencing mechanism was further studied. It was found that temperature and water activity were two crucial factors that would influence acyl migration kinetics. Determination of the kinetic parameters under different temperatures revealed that the acyl migration reaction rates were greatly promoted by the increasing of temperature. The acyl migration rates of 1,2-diglyceride and 2-monoglyceride were quite different from each other, which was found to be due to the different activation energies. Further study of how would water influence the acyl migration process showed that water activity rather than water content was a key factor that influenced acyl migration and the acyl migration rate would decrease with the increase of water activity. It was further revealed that water activity influenced the charge dispersion of the transition state, which ultimately influenced the reaction activation energy and then influenced the acyl migration rate.
- Li, Wei,Du, Wei,Li, Qiang,Sun, Ting,Liu, Dehua
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- Efficient synthesis of α-monoglycerides via solventless condensation of fatty acids with glycerol carbonate
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Highly pure α-monoglycerides (5a-e) were successfully prepared in high yields by the condensation of fatty acids such as lauric, myristic, palmitic, stearic and oleic (2a-e) with glycerol carbonate (4-hydroxymethyl-1,3- dioxolan-2-one) (1) in the presence
- Ghandi, Mehdi,Mostashari, Abdoljalil,Karegar, Mojgan,Barzegar, Mina
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- Enzyme, medium, and reaction engineering to design a low-cost, selective production method for mono- and dioleoylglycerols
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The selective enzymic production of mono- and diolein (MO, DO) was optimized at high yields. A comparative study of the following distinct enzymic reactions was conducted: ethyl oleate glycerolysis, triolein (TO) glycerolysis, and direct esterification. Solvent-free systems were compared with media that contained different solvents. Native, modified (with polyethylene glycol), and immobilized lipases were used. Mechanical resistance, the support effect on enzyme and glycerol dispersion and on process reproducibility, and hydrophilicity of the support were considered in the process optimization. We report the use of an immobilized lipase on an inorganic support (Celite), which has high activities in both solid-phase glycerolysis (99% reaction conversion) and esterification (100% conversion). The optimum conditions for the distinct reactions were compared by considering their selectivities, conversions, yields, and cost of the substrates. We found less costly and more selective processes in the absence of solvents for glycerolysis of triolein and direct esterification. Although glycerolysis was the most interesting process to produce diolein, esterification was better for monoolein preparation with this biocatalyst. The esterification reaction yielded 93 wt% of MO, in the absence of either TO or oleic acid (OA), at low cost because of the 100% reaction conversion. Similar costs of the substrates (10.6 and 10.1 $/g) were necessary to obtain 67 and 80 wt% of DO in esterification and glycerolysis, respectively. The glycerolysis conversion was 96%. In esterification, the product mixture was impure, with a high amount of residual OA due to the low conversion (59%). The high activity of PSL-Celite in these solid-phase reactions has an advantage over the reactions with nonimmobilized lipases due to the ease of enzyme recovery. The absence of organic solvents reduces the need for solvent removal from the reaction mixtures.
- Arcos,Otero
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- Non-ionic self-assembling amphiphilic polyester dendrimers as new drug delivery excipients
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Solubility enhancement of poorly soluble antibiotics via self-assembling nano systems could be a promising approach to effectively treat bacterial infections in the current scenario of evolving resistant species. The study in this paper reports the synthesis of novel biocompatible G2 and G3 polyester amphiphilic dendrimers (ADs) (GMOA-G2-OH, GMOA-G3-OH, GMS-G2-OH and GMS-G3-OH) and their application as: (i) solubility enhancers for fusidic acid (FSD) as a model antibiotic with poor aqueous solubility and (ii) as stearic stabilizers in the preparation of solid lipid nanoparticles (SLNs). Two different series of ADs from glycerol monostearate (GMS) and glycerol monooleate (GMOA) were synthesized and their structures were confirmed employing FT-IR, NMR (1H and 13C) and HR-MS. The MTT assay confirmed their non-toxicity to mammalian cells. The critical aggregation concentration value order for ADs was GMS-G3-OH (5 × 10?6 mol l?1) ?6 mol l?1) ?5 mol l?1). All ADs formed micelles in the size range of 6.48 ± 0.04 nm to 12.38 ± 0.36 nm. At 1% w/w concentration FSD solubility enhancement in GMOA-G2-OH, GMOA-G3-OH, GMS-G2-OH and GMS-G3-OH was 43, 11, 9.1 and 6.8-fold respectively compared to water. As GMOA-G2-OH enabled the highest solubility of FSD, it was further evaluated for its antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The minimum inhibitory concentration values for FSD with and without GMOA-G2-OH against S. aureus were 0.23 μg ml?1 and 0.53 μg ml?1 respectively whereas the values were 0.23 μg ml?1 and 0.39 μg ml?1 against MRSA respectively. These results suggested that GM-OA-G2 not only enhanced the solubility but also enhanced antibacterial potency of FSD. Furthermore, these ADs showed their potential as promising pharmaceutical excipients as they acted as stearic stabilizers in the preparation of SLNs. Using these ADs stable SLNs with zeta potential value in the range of ?15.30 ± 1.44 to ?38.46 ± 3.04 were formed.
- Sikwal, Dhiraj R.,Kalhapure, Rahul S.,Jadhav, Mahantesh,Rambharose, Sanjeev,Mocktar, Chunderika,Govender, Thirumala
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- Synthesis of monoglycerides by esterification of oleic acid with glycerol in heterogeneous catalytic process using tin-organic framework catalyst
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Selective synthesis of monoglycerides by esterification of glycerol with fatty acids is a difficult reaction because of immiscibility of reagents and the formation of di- and tri-glyceride by-products. In this work a heterogeneous catalytic process was conceived in which the reactant mixture was homogenized using tert-butanol solvent. Candidate catalysts were screened in the reaction of oleic acid with glycerol. While under such reaction conditions zeolites were rather inactive, metal-organic frameworks and, especially, tin-organic frameworks were found promising. A tin-organic framework (Sn-EOF) was most active and achieved ≥98 % monoglyceride selectivity at 40 % conversion in catalyzing esterification of oleic acid with glycerol at a low reaction temperature of 150 C. Leaching of tin from Sn-EOF catalyst was suppressed by limiting the amount of oleic acid in the starting mixture. Characterization of the acid sites of Sn-EOF by pyridine-chemisorption and FTIR revealed Lewis acidity to be responsible for the catalytic activity.
- Wee, Lik H.,Lescouet, Tristan,Fritsch, Julia,Bonino, Francesca,Rose, Marcus,Sui, Zhijun,Garrier, Eva,Packet, Dirk,Bordiga, Silvia,Kaskel, Stefan,Herskowitz, Moti,Farrusseng, David,Martens, Johan A.
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- Highly selective biocatalytic synthesis of monoacylglycerides in sponge-like ionic liquids
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The biocatalytic synthesis of monoacylglycerides (MAGs) was carried out by the direct esterification of fatty acids (i.e. capric, lauric, myristic, palmitic and oleic acids, respectively) with glycerol in different ionic liquids (ILs) based on cations with long alkyl side-chains (e.g. 1-hexadecyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [C16mim][NTf2], 1-dodecyl-3-methylimidazolium tetrafluoroborate [C12mim][BF4], etc.). Although all ILs have been shown as suitable reaction media for Novozym 435-catalyzed esterification of glycerol with free fatty acids, a high selectivity of MAGs was only observed in the [C12mim][BF4] case (e.g. up to 100% selectivity and 100% yield for monolaurin). Furthermore, as these ILs are temperature switchable ionic liquid/solid phases that behave as sponge-like systems, a straightforward protocol for IL-free MAG recovery, based on iterative centrifugations at controlled temperature, has been developed.
- Lozano, Pedro,Gomez, Celia,Nieto, Susana,Sanchez-Gomez, Gregorio,García-Verdugo, Eduardo,Luis, Santiago V.
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- High-selectivity synthesis method of long-chain fatty acid monoglyceride
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The invention belongs to the field of fatty acid and synthetic fatty acid glycerides and relates to a high-selectivity synthesis method of long-chain fatty acid monoglyceride, in particular to a high-selectivity synthesis method of long-chain fatty acid and synthetic fatty acid glycerides. The method comprises the steps that tetraethyl silicate and glycerin are subjected to alcoholysis reaction, and part of glycerin is esterified to generate glyceryl silicate; then the glyceryl silicate is subjected to esterification reaction with fatty acid to generate fatty acid glyceride; finally the high activity (instability) of silicate ester is utilized to achieve hydrolysis under mild conditions to synthesize the synthetic fatty acid glyceride at high selectivity. A by-product is safe and harmlessSiO2. Accordingly, the product with high monoglyceride content is obtained by using a simple process under mild conditions.
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Paragraph 0047; 0050
(2019/02/27)
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- Method for synthesizing high-content fatty acid monoglyceride and co-producing nano SiO2
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The invention belongs to the field of fatty acid glyceride synthesis and nano powder preparation, relates to a method for synthesizing high-content fatty acid monoglyceride and co-producing nano SiO2,and particularly relates to a method for synthesizing fatty acid monoglyceride and co-producing the nano SiO2 by long-chain fatty acid and glycerinum. The method comprises the following steps of: using silicon tetrachloride to react with the glycerinum, so as to enable the glycerinum to be partially esterified to generate silicic acid glyceride; and performing an esterification reaction with fatty acid to generate fatty acid silicic acid glyceride; finally using high-activity (instability) of silicate ester, hydrolyzing in a mild condition, synthesizing the high-content fatty acid monoglyceride, and by-producing SiO2 powder in a nano state. So that a fatty acid monoglyceride product is high-selectively obtained and nano SiO2 powder is co-produced by a simple technology in the mild condition.
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Paragraph 0049; 0052; 0053
(2019/03/28)
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- Method for synthesizing high content of fatty acid monoglyceride production of nano TiO2 The method of (by machine translation)
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The invention belongs to the fatty acid glyceride synthesis and nano powder preparation field. In particular to fatty acid and glycerin synthesis of fatty acid monoglyceride, and cogeneration nano TiO2 Method. Method of this invention is: for the reaction of titanium tetrachloride and glycerin, glycerol partial esterification, generating titanate glycerides. Then with the fatty acid esterification reaction, to generate fatty acid glyceride titanate. Finally the use of a titanate high activity (instability), hydrolysis under mild conditions, synthesizing high-content fatty acid monoglyceride, the pressure of the by-product TiO2 Powder. Thus a simple process, under mild conditions, a high content of fatty acid monoglyceride product, production of nano TiO2 Powder. (by machine translation)
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Paragraph 0049; 0052; 0053
(2019/03/28)
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- Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
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Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
- Joshi, Alaumy,Shaikh, Minhaj,Singh, Shubham,Rajendran, Abinaya,Mhetre, Amol,Kamat, Siddhesh S.
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p. 16953 - 16963
(2018/11/21)
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- Fatty acid monomer, preparation method and thermoplastic macromolecule synthesized through application
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The invention discloses a fatty acid monomer, a preparation method and a thermoplastic macromolecule synthesized through application. Tetramethyl guanidine and other catalysts are mainly utilized to catalyze a monomer containing halogen elements (Cl, Br and I) or halogen element and fatty acid, and the fatty acid monomer and thermoplastic macromolecule are obtained through efficient reaction. The application range can be thus widened by functionally improving the obtained fatty acid monomer and thermoplastic macromolecule. The reaction process is mild in condition, the catalytic efficiency of the catalysts is very high, few side reactions is produced, products are easy to separate and purify, and the fatty acid monomer and the thermoplastic macromolecule have a very high industrial application prospect.
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Paragraph 0024
(2017/09/02)
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- The chemical synthesis and preliminary biological studies of phosphodiester and phosphorothioate analogues of 2-methoxy-lysophosphatidylethanolamine
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The chemical synthesis of phosphorothioate/phosphodiester analogues of 2-methoxy-lysophosphatidylethanolamine has been described. For the preparation of phosphorothioate derivatives oxathiaphospholane approach has been employed. The phosphodiester compounds were prepared by OXONE oxidation of corresponding phosphorothioates. Each lysophospholipid analogue was synthesized as a series of four compounds, bearing different fatty acid residues both saturated (14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1→2 acyl migration. The cytotoxicity of newly synthesized 2-methoxy-lysophosphatidylethanolamine derivatives was evaluated with resazurin-based method in prostate cancer PC3 cell line. The highest reduction of cell viability was noted for LPE analogues containing myristoyl acyl chain.
- Sowińska, Agata,Rytczak, Przemys?aw,Gendaszewska-Darmach, Edyta,Drzazga, Anna,Kozio?kiewicz, Maria,Okruszek, Andrzej
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p. 3725 - 3729
(2016/07/21)
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- SYNTHESIS PROCESS FOR DIACETYL EPOXY GLYCERYL OLEATE
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The present invention relates to a process for the synthesis of diacetyl epoxy glyceryl oleate, comprising the steps of: a). esterification of glycerol and oleic acid at 115-190° C. for 1.5-4.5 hours in the presence of an esterification catalyst to obtain glyceryl monooleate; b). acetylation of glyceryl monooleate and an acetylating reagent at 90-160° C. for 2-10 hours in the presence of an acetylation catalyst to obtain diacetyl glyceryl oleate; c). epoxidation of diacetyl glyceryl oleate and hydrogen peroxide at 60-80° C. for 2-4 hours in the presence of an epoxidation catalyst and a weak acid to obtain diacetyl epoxy glyceryl oleate. The prepared diacetyl epoxy glyceryl oleate can be used as plasticizer in plastics, with the advantages of improved stability, good flowability, and high compatibility with plastics.
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Paragraph 0007; 0025; 0032
(2016/09/12)
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- TRIACYLGLYCEROL OLIGOMERS
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This application relates to triacylglycerol oligomers derived from the metathesis of natural oils. These oligomers are structure controlled dimers and quatrimers, and the effect of saturation, molecular size, and positional isomerization are also described herein.
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Paragraph 0046-0047
(2015/11/27)
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- Glycerolysis of methyl oleate on MgO: Experimental and theoretical study of the reaction selectivity
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The liquid-phase MgO-promoted glycerolysis of methyl oleate, a fatty acid methyl ester (FAME), to give acylglycerol products was studied both, experimentally and by density functional theory (DFT). Catalytic results showed that strongly basic low coordination O2- surface sites participate in kinetically relevant steps of the glycerolysis reaction. Changes in the selectivity toward the different mono- and diglyceride isomers were investigated by varying the reaction conditions. The main product was always α-glyceryl monooleate (α-MG), a monoglyceride with the ester fragment at one of the terminal positions of the glycerol molecule; the β-MG isomer, with the ester substituted at position 2 was obtained in much lower amounts. The molecular modeling of glycerol (Gly) and FAME adsorptions as well as of the glycerolysis reaction was carried out using periodic DFT calculations and a model of stepped MgO surface. Results indicated that FAME was more weakly adsorbed than Gly; the latter adsorbs on a coordinatively unsaturated surface O2- site with O-H bond breaking at position 2 of the Gly molecule, giving therefore a surface β-glyceroxide species. Calculations explained the apparent contradiction between the preferential formation of the α-MG isomer and the energetically favored dissociation of the secondary OH group of Gly that leads to the β-glyceroxide species. They predict that the β-glyceroxide species participates in the pathways conducting to both, α- and β-MG isomers. Synthesis of α-MG occurs by C-O coupling of β-glyceroxide with FAME at one of the two primary OH groups of the β-glyceroxide species. Two transition states (TS) and a tetrahedral intermediate (TI) are involved in both, α-MG and β-MG isomer formation. However, the pathway toward β-MG is limited by the large sterical effects associated to the TI formation. Contrarily, the TI leading to α-MG is relatively easy to form.
- Belelli,Ferretti,Apesteguía,Ferullo,Di Cosimo
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p. 132 - 144
(2015/09/28)
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- Zirconium phenyl phosphonate phosphite as a highly active, reusable, solid acid catalyst for producing fatty acid polyol esters
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The application of zirconium phenyl phosphonate phosphite (ZrPP) as a solid acid catalyst for producing polyol esters by esterification of glycerol or trimethylolpropane with a fatty acid (C8-C18.1) is reported for the first time. ZrPP exhibits high catalytic activity and in particular, (di + tri) esters selectivity (92.3 mol%). These esters of polyols are known for their application as biolubricants. The catalyst prepared using phosphorous acid to phenyl phosphonic acid molar ratio of 3:1 was found superior. The influence of process parameters on activity and selectivity of the catalyst was investigated. ZrPP was reusable in at least three recycling experiments. Hydrophobicity due to exposed phenyl groups on the surface is the possible cause for superior esterification activity of this novel, solid catalyst.
- Varhadi, Poonam,Kotwal, Mehejabeen,Srinivas
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p. 129 - 136
(2013/07/26)
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- An improved method for the synthesis of 1-monoolein
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Monoacylglycerols (MAGs) are precursors for the synthesis of many active lipids and an important amphiphilic emulsifiers which are widely used in food, pharmaceutical, and cosmetic industries. In this study, we reported an improved method for the synthesis of 1-monoolein using 1,2-acetonide glycerol as starting reactant. Firstly, commercial oleic acid was purified using our previous method and then 1,2-acetonide-3-oleoylglycerol was synthesized by the esterification of 1,2-acetonide glycerol with purified oleic acid using Novozym 435 lipase as catalyst. Finally, the cleavage of unpurified 1,2-acetonide-3-oleoylglycerol in methanol was conducted to obtain 1-monoolein. The effects of reaction system, addition amount of solvent, lipase load, reaction temperature and time on 1,2-acetonide-3-oleoylglycerol content in the crude reaction mixture were investigated. Under the optimal conditions, 94.6% 1,2-acetonide-3-oleoylglycerol in crude reaction mixture was obtained. 1-Monoolein was synthesized further by cleaving unpurified 1,2-acetonide-3-oleoylglycerol in methanol at room temperature with Amberlyst-15 resin as catalyst. The cleavage reaction resulted in the formation of 76.5% 1-monoolein and 96.2% 1-monoolein was obtained at 72.8% yield after repeated recrystallization in hexane to remove nonpolar impurities and water washing to remove glycerol. The main novelties for the synthesis of 1-monoolein are the use of Novozym 435 lipase instead of chemical catalysts used in previous studies to catalyze the esterification of 1,2-acetnode glycerol with free fatty acids and scalable crystallization method used instead of column chromatography to purify 1-monoolein.
- Wang, Xiaosan,Jin, Qingzhe,Wang, Tong,Huang, Jianhua,Wang, Xingguo
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p. 130 - 136
(2013/10/01)
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- 1-O-Alkyl (di)glycerol ethers synthesis from methyl esters and triglycerides by two pathways: Catalytic reductive alkylation and transesterification/reduction
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From available and bio-sourced methyl esters, monoglycerides or oleic sunflower refined oil, the corresponding 1-O-alkyl (di)glycerol ethers were obtained in both high yields and selectivity by two different pathways. With methyl esters, a reductive alkylation with (di)glycerol was realized under 50 bar hydrogen pressure in the presence of 1 mol% of Pd/C and an acid co-catalyst. A second two step procedure was evaluated from methyl esters or triolein and consisted of a first transesterification to the corresponding monoglyceride with a BaO/Al2O3 catalyst, then its reduction to the desired glycerol monoether with a recyclable heterogeneous catalytic system Pd/C and Amberlyst 35 under H2 pressure. In addition, a mechanism for the reaction was also proposed.
- Sutter, Marc,Dayoub, Wissam,Metay, Estelle,Raoul, Yann,Lemaire, Marc
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supporting information
p. 786 - 797
(2013/04/24)
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- The chemical synthesis of metabolically stabilized 2-OMe-LPA analogues and preliminary studies of their inhibitory activity toward autotaxin
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The chemical synthesis of five new metabolically stabilized 2-OMe-LPA analogues (1a-e) possessing different fatty acid residues has been performed by phosphorylation of corresponding 1-O-acyl-2-OMe-glycerols which were prepared by multistep process from racemic glycidol. The now analogues were subjected to biological characterization as autotaxin inhibitors using the FRET-based, synthetic ATX substrate FS-3. Among tested compounds 1-O-oleoyl-2-OMe-LPA (1e) appeared to be the most potent, showing ATX inhibitory activity similar to that of unmodified 1-O-oleoyl-LPA. Parallel testing showed, that similar trend was also observed for corresponding 1-O-acyl-2-OMe-phosphorothioates (2a-e, synthesized as described by us previously). 1-O-oleoyl-2-OMe-LPA (1e) was found to be resistant toward alkaline phosphatase as opposed to unmodified 1-O-oleoyl-LPA.
- Gendaszewska-Darmach, Edyta,Laska, Edyta,Rytczak, Przemys?aw,Okruszek, Andrzej
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supporting information; body text
p. 2698 - 2700
(2012/05/20)
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- Pheromone synthesis. Part 253: Synthesis of the racemates and enantiomers of triglycerides of male Drosophila fruit flies with special emphasis on the preparation of enantiomerically pure 1-monoglycerides
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The racemates and enantiomers of triglycerides 1aee (2,3-ditigloyloxypropyl esters of palmitic, palmitoleic, stearic, oleic, and linoleic acids) of male Drosophila fruit flies were synthesized in three steps from the racemate and enantiomers of 2,3-acetoneglycerol (2) via 1-monoglycerides 4aee derived from the above fatty acids. Appropriate conditions were established for the preparation of enantiomerically pure 1-monoglycerides 4aee, and their enantiomeric purities were determined by NMR analysis of the corresponding bis-(R)-MTPA esters.
- Mori, Kenji
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experimental part
p. 8441 - 8449
(2012/10/07)
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- Influence of fatty acid desaturation on spontaneous acyl migration in 2-monoacylglycerols
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The effect of desaturation from the C9 to the C15 carbon of 2-monoacylglycerol (2-MAG) fatty acids on spontaneous acyl migration is described. Three 2-MAG species, 2-monooleoylglycerol (C18:1 cis-Δ9), 2-monolinoleoylglycerol (C18:2 cis-Δ9,12), and 2-monolinolenoylglycerol (C18:3 cis-Δ9,12,15) were synthesized by lipase-catalyzed ethanolysis of their respective triacylglycerols and isolated in >60 % yield and at 2-MAG purities of >95 % relative to 1-monoacylglycerol (1-MAG). 1H-NMR spectroscopy was used to monitor the spontaneous acyl migration of the 2-MAG species over a temperature range from 20 to 80 °C. The relative energies of activation calculated from the Arrhenius relationships of the 2-MAG acyl migration rate constants were 73.3, 68.0, and 72.9 kJ mol-1 for the three 2-MAG species, respectively. Density functional calculations performed using the B3LYP functional at the 6-31+G* basis set on the three ketal ring intermediate of the three 2-MAG species followed a similar trend with a lack of relative energetic preference associated with the degree of desaturation. The kinetically determined relative activation energies were approximately twofold higher than the theoretical relative Gibbs free energies of the intermediates, suggesting that other factors influence acyl migration. In general, increasing desaturation after the C9 carbon of 2-MAG fatty acids had no appreciable effect on acyl migration rates. AOCS (outside the USA) 2012.
- Compton, David L.,Laszlo, Joseph A.,Appell, Michael,Vermillion, Karl E.,Evans, Kervin O.
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p. 2259 - 2267
(2013/01/15)
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- Efficient synthesis of unsaturated 1-monoacyl glycerols for in meso crystallization of membrane proteins
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A highly efficient synthesis of unsaturated 1-monoacyl glycerols was established to fulfill the pressing need for materials that form lipidic mesophases utilized in membrane protein crystallization. Georg Thieme Verlag Stuttgart.
- Fu, Yu,Weng, Yue,Hong, Wen-Xu,Zhang, Qinghai
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p. 809 - 812
(2011/06/21)
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- Glycerol acyl-transfer kinetics of a circular permutated Candida antarctica lipase B
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Triacylglycerols containing a high abundance of unusual fatty acids, such as γ-linolenic acid, or novel arylaliphatic acids, such as ferulic acid, are useful in pharmaceutical and cosmeceutical applications. Candida antarctica lipase B (CALB) is quite often used for non-aqueous synthesis, although the wild-type enzyme can be rather slow with bulky and sterically hindered acyl donor substrates. The catalytic performance of a circularly permutated variant of CALB, cp283, with various acyl donors and glycerol was examined. In comparison to wild-type CALB, butyl oleate and ethyl γ-linolenate glycerolysis rates were 2.2- and 4.0-fold greater, respectively. Cp283 showed substrate inhibition by glycerol, which was not the case with the wild-type version. With either ethyl ferulate or vinyl ferulate acyl donors, cp283 matched the performance of wild-type CALB. Changes in active site accessibility resulting from circular permutation led to increased catalytic rates for bulky fatty acid esters but did not overcome the steric hindrance or energetic limitations experienced by arylaliphatic esters.
- Laszlo, Joseph A.,Yu, Ying,Lutz, Stefan,Compton, David L.
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scheme or table
p. 175 - 180
(2012/07/01)
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- The chemical synthesis of phosphorothioate and phosphorodithioate analogues of lysophosphatidic acid (LPA) and cyclic phosphatidic acid (CPA)
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The chemical synthesis of new sulfur analogues of lysophospholipids has been described, including phosphorothioate/phosphorodithioate derivatives of lysophosphatidic acids (LPA) and phosphorothioate/phosphorodithioate derivatives of cyclic phosphatidic acids (cPA). For the preparation of LPA and cPA derivatives both oxathiaphospholane and dithiaphospholane approaches have been employed. Each lysophospholipid analogue has been synthesized as a series of five compounds, bearing five different fatty acid residues, both saturated (12:0, 14:0, 16:0, 18:0) and unsaturated (18:1), in the form of ammonium salts. The phosphorodithioate analogues of LPA were obtained as triethylammonium salts, however these were not stable and decomposed when transformed into the ammonium salt by ion exchange in aqueous methanol solution. The new sulfur analogues of LPA and cPA may share interesting biological properties of their parent compounds, and previously synthesized derivatives may behave as regulators of many metabolic processes and hopefully show new biological activity.
- Rytczak, Przemyslaw,Koziolkiewicz, Maria,Okruszek, Andrzej
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experimental part
p. 1008 - 1017
(2010/08/05)
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- Preparation of diacid 1,3-diacylglycerols
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A complete methodology (including synthesis, purification and analysis) for the preparation of 1,3-DAG is described. For a successful synthesis project, the strengths and weaknesses of each particular process should be taken into account and measures taken to offset or balance potential weaknesses. To this end, we describe some of the challenges associated with: chemically and enzymatically catalyzed acylglycerol syntheses; recrystallization and flash chromatography for purification of partial acylglycerols; and thin-layer chromatography (TLC) separation of DAG. For this work, 1-MAG intermediates and subsequent diacid 1,3-DAG were prepared using non-enzymatic methods, whereas, monoacid 1,3-DAG were prepared by enzymatic methods. It was not always possible to obtain pure samples of target compounds-in recrystallizations this is due to solid solution formation and co-crystallization and in chromatographic separations it is due to co-elution of components with similar Rf. Furthermore, TLC Rf of DAG is determined by two main factors: acyl chain length and positional isomerism. Interestingly, while the role of positional isomerism is well-known, the role of acyl chain length in these separations has only recently come to light.
- Craven, R. John,Lencki, Robert W.
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experimental part
p. 1281 - 1291
(2011/08/21)
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- Monoglycerides from the brown alga Sargassum sagamianum: Isolation, synthesis, and biological activity
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Polyunsaturated fatty acid-derived monoglycerides were characterized from the marine brown alga Sargassum sagamianum, collected from Jeju Island, Korea. A new compound of this structural class was isolated and determined to be 1-octadecatetraenoyl glycerol, by combined spectroscopic methods. Based on the structures and bioactivity of these compounds, a series of monoglycerides were synthesized using glycerol and various fatty acids. Several compounds exhibited moderate to significant inhibition of phospholipase A2 and cyclooxygenase-2.
- Chang, Hyeun Wook,Jang, Kyoung Hwa,Lee, Doohyun,Kang, Hee Ryong,Kim, Tae-Yoon,Lee, Bong Ho,Choi, Byoung Wook,Kim, Sanghee,Shin, Jongheon
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body text
p. 3589 - 3592
(2009/04/11)
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- Regioselective and stereospecific acylation across oxirane- and silyloxy systems as a novel strategy to the synthesis of enantiomerically pure mono-, di- and triglycerides
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A trifluoroacetate-catalyzed opening of the oxirane ring of glycidyl derivatives bearing allylic acyl or alkyl functionalities with trifluoroacetic anhydride (TFAA), provides an efficient entry to configurationally homogeneous 1(3)-acyl- or 1(3)-O-alkyl-sn-glycerols. Selective introduction of tert-butyldimethylsilyl- (TBDMS), or triisopropylsilyl- (TIPS) transient protections at the terminal sites within these key intermediates secures 1(3)-acyl- or 1(3)-O-alkyl-3(1)-O-TBDMS (or TIPS)-sn-glycerols as general bifunctional precursors to 1,2(2,3)-diacyl-, 1(3)-O-alkyl-2-acyl- and 1,3-diacyl-sn-glycerols and hence triester isosters. Incorporation of a requisite acyl residue at the central carbon of the silylated synthons with a subsequent Et3N·3HF-promoted, direct trichloroacetylation across the siloxy system by trichloroacetic anhydride (TCAA), followed by cleavage of the trichloroacetyl group, affords the respective 1,2(2,3)-diacyl- or 1(3)-O-alkyl-2-acyl-sn-glycerols. Alternatively, a reaction sequence involving: (i) attachment of a trichloroacetyl fragment at the stereogenic C2-centre of the monosilylated glycerides; (ii) replacement of the silyl moiety by a short- or long-chain carboxylic acid residue by means of the acylating agent: tetra-n-butylammonium bromide (TBABr)-carboxylic acid anhydride (CAA)-trimethylsilyl bromide (TMSBr); and (iii) removal of the trichloroacetyl replacement, provides pure 1,3-diacyl-sn-glycerols. The TBABr-CAA-TMSBr reagent system allows also a one-step conversion of 1,2-diacylglycerol silyl ethers into homochiral triglycerides with predefined asymmetry and degree of unsaturation. These compounds can also be accessed via a two-step one-pot approach where the trichloroacetyl derivatives of 1,2(2,3)- or 1,3-diacyl-sn-glycerols serve as triester building blocks for establishing the third ester bond at preselected C3(1)- or C2-positions within the glycerol skeleton at the very last synthetic stage. In all instances, the target compounds were produced under mild conditions, in high enantiomeric purity, and in practically quantitative yields. The Royal Society of Chemistry 2007.
- Stamatov, Stephan D.,Stawinski, Jacek
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p. 3787 - 3800
(2008/10/09)
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- PROCESS FOR THE PRODUCTION OF A POLYOL MONOMER
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A process for preparing palm-based polyol monomer includes reacting unsaturated fatty acids or its corresponding triglycerides with polyhydric alcohol. In particular, one example uses oleic acid with about 70% purity as the starting material for preparing the polyol monomer. Moreover, another example uses refined, bleached, and deodorised (RBD) palm olein as an alternative to oleic acid as the starting material. The preparation of the polyol monomer involves the production of monoglyceride of unsaturated fatty acids, which was further epoxidised with peracid and finally ring opened with polyhydric alcohols. Such polyol monomer is used as a raw material for the production of various types of polyurethane products.
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Page/Page column 3
(2008/06/13)
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- Stereospecific and regioselective opening of an oxirane system. A new efficient entry to 1- or 3-monoacyl- and 1- or 3-monoalkyl-sn-glycerols
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Acyl or alkyl glycidols in the presence of trifluoroacetic anhydride (TFAA) and trifluoroacetate anions, undergo a regioselective and stereospecific opening of the oxirane system to produce the bis(trifluoroacetylated) derivatives, from which the corresponding 1(3)-monoacyl-sn-glycerols or 1(3)-monoalkyl-sn-glycerols can be obtained directly in high purity (>99%) and in quantitative yields.
- Stamatov, Stephan D.,Stawinski, Jacek
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p. 1601 - 1605
(2007/10/03)
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- Functionalized polymers for medical applications
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The present invention is directed to synthetic, biodegradable, biocompatible polymers that are the reaction product of an α,β-unsaturated polybasic acid or derivative thereof and a monoglyceride, and which further contain pended thereto a functional agent, and to medical devices and compositions containing such polymers.
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- Modular approach to the synthesis of unsaturated 1-monoacyl glycerols
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A modular synthesis of unsaturated 1-monoacylglycerols (1) from cis-1-iodo-1-alkenes [cis-RCH=CHI] and unsaturated carboxylic acids [CH 2=CH(CH2)nCO2H] is described. The method revolves around a Suzuki coupling to establish olefin geometry.
- Coleman, Bridgett E.,Cwynar, Valerie,Hart, David J.,Havas, Fabien,Jakkam, Madan Mohan,Patterson, Suzanne,Ridenour, Sam,Schmidt, Michael,Smith, Eboney,Wells, Angela J.
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p. 1339 - 1342
(2007/10/03)
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- Wetting agent composition for agricultural chemicals
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The present invention provides an agrochemical spreader composition having excellent low-temperature stability. Specifically, the present invention provides an agrochemical spreader composition comprising a surfactant (A) having a melting point of 20 to 60° C., a surfactant (B) having a melting point of not more than 0° C. and water in a specific ratio.
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- Host-recognizing kairomones for parasitic wasp, Anisopteromalus calandrae, from larvae of azuki bean weevil, Callosobruchus chinensis.
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Host-recognizing kairomones for the stinging behavior of the parasitic wasp, Anisopteromalus calandrae, were identified on host azuki bean weevil larvae, Callosobruchus chinensis (L.). The kairomones were extracted with acetone from Chinese green beans, from which emerged wasps and host weevils had been removed. The kairomones are a mixture of triacylglycerols and fatty acids, each of which is separately active, and with no observable synergistic effect between them. These compounds are known to be constituents of an oviposition-marking pheromone of host azuki bean weevils. However, they differ from the previously reported saturated hydrocarbons and diacylglycerols of the kairomone that another parasitic wasp, Dinarmus basalis, uses for the host recognition of C. chinensis. Thus, A. calandrae and D. basalis selectively utilize different constituents of the oviposition-marking pheromone of C. chinensis as host-recognizing kairomones.
- Onodera, Junko,Matsuyama, Shigeru,Suzuki, Takahisa,Fujii, Koichi
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p. 1209 - 1220
(2007/10/03)
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- Osteoblast-specific mitogens and drugs containing such compounds
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Osteoblast-specific mitogens and drugs containing such compounds can be used for treating metabolic bone diseases. These compounds include lysophosphatidylic acid derivatives selected from the group consisting of compounds of formula: wherein R1=alkenyl or alkynyl having from 6 to 24 carbon atoms; n=0-12; X=oxygen or NH; the compounds (all-cis-5,8,11,14)-eicosatetraenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9, cis-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-9,12,15)-octadecatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and erucic acid 2-hydroxy-3-phosphonooxypropylester being excluded, and the physiologically tolerable salts, esters, optically active forms, and racemates of said compounds, and derivatives of said compounds, salts, esters, optically active forms and racemates which can be metabolized in vivo to yield the corresponding compound of formula (I).
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- Enzymatic synthesis of symmetrical 1,3-diacylglycerols by direct esterification of glycerol in solvent-free system
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1,3-Diacylglycerols were synthesized by direct esterification of glycerol with free fatty acids in a solvent-free system. Free fatty acids with relatively low melting points (45°C) such as unsaturated and medium-chain saturated fatty acids were used. With stoichiometric ratios of the reactants and water removal by evaporation at 3 mm Hg vacuum applied at 1 h and thereafter, the maximal 1,3-diacylglycerol content in the reaction mixture was: 84.6% for 1,3-dicaprylin, 84.4% for 1,3-dicaprin, 74.3% for 1,3-dilinolein, 71.7% for 1,3-dieicosapentaenoin, 67.4% for 1,3-dilaurin, and 61.1% for 1,3-diolein. Some of the system's parameters (temperature, water removal, and molar ratio of the reactants) were optimized for the production of 1,3-dicaprylin, and the maximal yield reached 98%. The product was used for the chemical synthesis of 1,3-dicapryloyl-2-eicosapentaenoylglycerol. The yield after purification was 42%, and the purity of the triacylglycerol was 98% (both 1,3-dicapryloyl-2-eicosapentaenoylglycerol and 1,2-dicapryloyl-3-eicosapentaenoylglycerol included) by gas chromatographic analysis, of which 90% was the desired structured triacylglycerol (1,3-dicapryloyl-2-eicosapentaenoylglycerol) as determined by silver ion high-performance liquid chromatographic analysis.
- Rosu, Roxana,Yasui, Mamoru,Iwasaki, Yugo,Yamane, Tsuneo
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p. 839 - 843
(2007/10/03)
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- Study of the effect of DATEM. 1. Influence of fatty acid chain length on rheology and baking
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To answer the question of which fatty acid residue is the most effective, diacetyltartaric esters of monoglycerides (DATEMs) with fatty acids of chain lengths 6:0-20:0 were synthesized. The activity of synthesized DATEMs and commercial DATEM products was studied by means of rheological methods and a microscale baking test with 10 g of flour. Variation of the acyl residue from 6:0 to 22:0 showed that stearic acid (18:0) had the best effect on the baking activity of DATEM (loaf volume increased by 62%). DATEMs containing unsaturated fatty acids (18:1, 18:2) or DATEMs produced from diacylglycerols instead of monoacylglycerols showed a slight increase of the loaf volumes. A slight effect of DATEM on the rheology of dough was observed. However, much greater was the effect on the gluten isolated from doughs prepared with DATEM. The resistance of gluten to extension was increased after the addition of increasing amounts of DATEM (0.1-0.5%). Within the series of DATEMs derived from the homologous series of monoacylglycerols the product based on glycerol monostearate (18:0) showed a maximum increase of the gluten resistance.
- Koehler, Peter,Grosch, Werner
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p. 1863 - 1869
(2007/10/03)
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- Monoacetyldiglycerides as new Ca2+ mobilizing agents in rat pancreatic acinar cells.
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Several monoacetyldiglycerides were synthesized from glycerol in search for new Ca2+ mobilizing agent in vitro. All monoacetyldiglycerides except linolenoyl and phenlycyclopropylcarbonyl derivatives showed activity toward Ca2+ release in pancreatic acinar cells. Linoleoyl and docosahexaenoyl derivatives were chosen for further test and exhibited unique activity.
- Han,Cho,Kim,Seo,Moon,Jhon
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- Propofol microdroplet formulations
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Formulations of phospholipid-coated microdroplets of propofol devoid of fats and triglycerides provide chronic sedation over extended periods of time without fat overload. Being free of nutrients that support bacterial growth, these microdroplet formulations are bacteriosatic and bactericidal (e.g. self-sterilizing) and thus have extended shelf life.
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- Enzymatic esterification of glycerol III. Lipase-catalyzed synthesis of regioisomerically pure 1,3-sn-diacylglycerols and 1(3)-rac-monoacylglycerols derived from unsaturated fatty acids
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Lipases that display high regioselectivities and broad substrate tolerance were used as catalysts for the efficient esterification of glycerol under the conditions of irreversible acyl transfer. A variety of unsaturated fatty acids, such as oleic, linoleic, erucic, ricinolic, hydroxystearic and coriolic acid, were used for this purpose in the form of their vinyl esters. Suitable biocatalysts were chosen on the basis of systematic screening experiments regarding their regioselectivities (RE) and substrate tolerances. Distinct differences were found and expressed in numerical RE values as a measure for differences of these biocatalysts as being specific, selective, and nonspecific. Based on these experiments, a variety of molecules were synthesized on a preparative scale (>150 mmol) in good yield (ca. 85%) and with high regioisomerical purities (>95% RE).
- Waldinger,Schneider
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p. 1513 - 1519
(2007/10/03)
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- Synthesis of Mono- and Diglycerides In Water-in-Oil Microemulsions
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Enzyme-Catalyzed esterification was carried out in single-phase, oil-continuous microemulsions.The lipozyme was solubilized, along with glycerol and water, in the aqueous core of water / diethylhexyl sodium sulfosuccinate / hydrocarbon microemulsion system.Upon addition of fatty acid, mono- and diglycerides were formed, due to the esterification reaction taking place at the interface of the droplets in the microemulsion.The initial rate of conversion of oleic acid increases with oil chainlength of the continuous phase whereas final conversion is maximum for hexane.The conversion of stearic acid is 30percent whereas conversion of oleic acid is 70percent.The percent conversion of various fatty acids in the same continuous medium increases with fatty acid chainlength.The oleic acid / glycerol ratio is an important parameter for optimum conversion of oleic acid into glycerides.The yield can be increased by subsequent addition of glycerol after equilibrium is reached.High-performance liquid chromatography analysis of samples from microemulsions showes the presence of mono- and diglycerides.Possible mechanisms for the abovementioned effects are discussed. KEY WORDS: AOT, diglyceride, esterification, fatty acid, glycerol, hydrolysis, lipase, microemulsion, monoglyceride, reversed micelle.
- Singh, C. P.,Shah, D. O.,Holmberg, Krister
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p. 583 - 587
(2007/10/02)
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- Sustained release delivery of water-soluble bio-molecules and drugs using phospholipid-coated microcrystals, microdroplets and high-concentration liposomes
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The novel uses of the phospholipid-coated microcrystal in the delivery of water-soluble biomolecules such as polypeptides and proteins. The proteins are rendered insoluble by complexation and the resulting material forms the solid core of the phospholipid-coated particle. Alternatively, the proteins, bio-molecules or drugs can be entrapped in water-soluble form between the membranous layers of the coated microcrystal. All types of phospholipid microcrystals can incorporate 5 nm to 10 um diameter iron oxide particles to allow for manipulation by magnetic fields. Water-soluble bio-molecules including proteins, peptides, and drugs can be entrapped and retained with long shelf life in liposomes at high concentrations, provided that the phospholipid concentration is greater than 10% (w/v) such that greater than 50% of the system volume is enclosed within phospholipid membranes. Both the phospholipid-coated microcrystal and the phospholipid-coated microdroplet can be used as vaccine adjuvants.
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- Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs
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Water-insoluble drugs are rendered injectable by formulation as aqueous suspensions of phospholipid-coated microcrystals. The crystalline drug is reduced to 50 nm to 10 um dimensions by sonication or other processes inducing high shear in the presence of phospholipid or other membrane-forming amphipathic lipid. The membrane-forming lipid stabilizes the microcrystal by both hydrophobic and hydrophilic interactions, coating and enveloping it and thus protecting it from coalescence, and rendering the drug substance in solid form less irritating to tissue. Additional protection against coalescence is obtained by a secondary coating by additional membrane-forming lipid in vesicular form associated with and surrounding but not enveloping the lipid-encapsulated drug particles. Tissue-compatible formulations containing drug in concentrations up to 40% (w/v) are described. The preparations can be injected intra-lesionally and in numerous other sites, including intra-venous, intra-arterial, intra-muscular, intra-dermal, etc. The disclosure describes examples of formulations and pharmacokinetic data with antibiotics, anthelmintic drugs, antiinflammatory drugs, local and general anesthetics, and biologicals.
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