Fatty Acid Diesters Research Articles

Nuclear magnetic resonance characterization of reaction products of interesterification of peracetylated α‐d‐glucopyranose and fatty acid methyl esters

AbstractMono‐ and diesters of fatty acids of peracetylated α‐d‐glucopyranose were prepared by chemical interesterification. Substituent‐induced chemical shift effects on the carbonyl carbons rather than the ring carbons and proton atoms unambiguosly show the fatty acyl substituents to be at C1 in the monosubstituted, and at C1 and C6 in the disubstituted products. 1H nuclear magnetic resonance (NMR) integration data before and after interesterification complemented 13C chemical shift data in verifying the molecular structures. Empirical data from classical 1H and 13C NMR experiments thus provide a simple self‐contained method for determining the number and position of fatty acyl substituents, and the anomeric compositions of peracetylated glucose fatty esters.

Final Report on the Safety Assessment of Propylene Glycol (PG) Dicaprylate, PG Dicaprylate/Dicaprate, PG Dicocoate, PG Dipelargonate, PG Isostearate, PG Laurate, PG Myristate, PG Oleate, PG Oleate SE, PG Dioleate, PG Dicaprate, PG Diisostearate, and PG Dilaurate

The Propylene Glycol Dicaprylate family of ingredients includes several esters and diesters of Propylene Glycol and fatty acids. These ingredients are used in cosmetic formulations as skin conditioning agents, viscosity increasing agents, and surfactants. Two skin irritation studies (minimal to no irritation) and a comedogenicity study (insignificant comedogen) on Propylene Glycol Dicaprylate/Dicaprate and a skin irritation study (slight) and an acute oral toxicity study (nontoxic) on Propylene Glycol Laurate were available. Available data were also found indicating that Propylene Glycol Dicaprylate/Dicaprate and Propylene Glycol Dipelargonate may enhance the skin penetration of other chemicals. Because of the ability of these Polyethylene Glycol esters and diesters to enhance penetration of other agents, it was recommended that care be taken in using these and other Polyethylene Glycol esters and diesters in cosmetic products. Previous Cosmetic Ingredient Review safety assessments of related ingredients, including Polyethylene Glycol, Polyethylene Glycol Stearate, Coconut Oils and Acids, Isostearic Acid, Lauric Acid, Myristic Acid, Oleic Acid, and Caprylic/Capric Triglyceride, were summarized. Included were mutagenicity, chronic toxicity, and skin irritation and sensitization data. Based in part on the limited data available on the ingredients included in the report, but more so on the previous reviews of chemically similar moieties, it was concluded that Propylene Glycol Dicaprylate, Propylene Glycol Dicaprylate/Dicaprate, Propylene Glycol Dicocoate, Propylene Glycol Dipelargonate, Propylene Glycol Isostearate, Propylene Glycol Laurate, Propylene Glycol Myristate, Propylene Glycol Oleate, Propylene Glycol Oleate SE, Propylene Glycol Dioleate, Propylene Glycol Dicaprate, Propylene Glycol Diisostearate, and Propylene Glycol Dilaurate are safe for use as cosmetic ingredients in the present practices of use.

Final Report on the Safety Assessment of Propylene Glycol (PG) Dicaprylate, PG Dicaprylate/Dicaprate, PG Dicocoate, PG Dipelargonate, PG Isostearate, PG Laurate, PG Myristate, PG Oleate, PG Oleate SE, PG Dioleate, PG Dicaprate, PG Diisostearate, and PG Dilaurate

The Propylene Glycol Dicaprylate family of ingredients includes several esters and diesters of Propylene Glycol and fatty acids. These ingredients are used in cosmetic formulations as skin conditioning agents, viscosity increasing agents, and surfactants. Two skin irritation studies (minimal to no irritation) and a comedogenicity study (insignificant comedogen) on Propylene Glycol Dicaprylate/Dicaprate and a skin irritation study (slight) and an acute oral toxicity study (nontoxic) on Propylene Glycol Laurate were available. Available data were also found indicating that Propylene Glycol Dicaprylate/Dicaprate and Propylene Glycol Dipelargonate may enhance the skin penetration of other chemicals. Because of the ability of these Polyethylene Glycol esters and diesters to enhance penetration of other agents, it was recommended that care be taken in using these and other Polyethylene Glycol esters and diesters in cosmetic products. Previous Cosmetic Ingredient Review safety assessments of related ingredients, including Polyethylene Glycol, Polyethylene Glycol Stearate, Coconut Oils and Acids, Isostearic Acid, Lauric Acid, Myristic Acid, Oleic Acid, and Caprylic/Capric Triglyceride, were summarized. Included were mutagenicity, chronic toxicity, and skin irritation and sensitization data. Based in part on the limited data available on the ingredients included in the report, but more so on the previous reviews of chemically similar moieties, it was concluded that Propylene Glycol Dicaprylate, Propylene Glycol Dicaprylate/Dicaprate, Propylene Glycol Dicocoate, Propylene Glycol Dipelargonate, Propylene Glycol Isostearate, Propylene Glycol Laurate, Propylene Glycol Myristate, Propylene Glycol Oleate, Propylene Glycol Oleate SE, Propylene Glycol Dioleate, Propylene Glycol Dicaprate, Propylene Glycol Diisostearate, and Propylene Glycol Dilaurate are safe for use as cosmetic ingredients in the present practices of use.

Epidemiologic Evidence for a New Class of Compounds Associated with Toxic Oil Syndrome

Toxic oil syndrome appeared in epidemic form in Spain in 1981. Epidemiologic studies have demonstrated that illness was caused by consumption of rapeseed oil that had been denatured with aniline. Chemical analyses of oil specimens conducted in conjunction with epidemiologic studies have established that consumption of specific oils containing fatty acid anilide contaminants was associated with increased risk for disease. New chemical analytic methods identified a family of compounds, the di-fatty acid esters of phenylamino propane-diol, and one of these compounds, the 1,2-di-oleyl ester of 3-(N-phenylamino)-1,2-propanediol (DPAP), has been found to be more strongly associated with disease status than the fatty acid anilides. We found the odds ratio for exposure to DPAP (OR = 26.4, 95% CI = 6.4-76.3) is much higher than the odds ratio for exposure to oleyl anilide (OR = 4.1, 95% CI = 2.2-7.8), implying that exposure to DPAP was a more relevant risk factor for development of toxic oil syndrome than exposure to oleyl anilide. In this paper, we review and present analyses of data from multiple studies of the possible etiologic role of DPAP in toxic oil syndrome. The presence of DPAP in oil collected from affected and unaffected households was a more specific correlate of case relatedness than was the presence of fatty acid anilides, and it was equally sensitive. Moreover, DPAP was found in oil from the only refinery whose oil was clearly associated with illness.

Xanthophyll Esters in Human Skin

Carotenol fatty acid esters in various fruits and vegetables are sources of carotenoids for humans and are cleaved during intestinal absorption to yield the parent xanthophyll. In the present study we demonstrate that low amounts of carotenol esters are present in human skin. Eighteen different carotenol fatty acid esters were separated in extracts from human skin by means of reversed-phase high-performance liquid chromatography. After saponification of tissue samples, lutein, zeaxanthin, 2′,3′-anhydrolutein, α-cryptoxanthin and β-cryptoxanthin were identified as the major parent carotenoids. Based on comparison with synthetic reference compounds, several carotenol mono- and di-fatty acid esters were tentatively assigned, ranging from linoleate to stearate; the levels are low, in the range of pmol/g human skin, i.e., several orders of magnitude lower than that of β-carotene. Carotenol esters in human skin may be formed by reesterification of xanthophylls following absorption. Also, very small amounts of esters may circulate in the blood and subsequently accumulate in tissues such as skin.

Synthesis of tritium and carbon-14 labelled linoleic acid esters of 3-phenylamino-1,2-propanediol, compounds potentially involved in the etiology of the Toxic Oil Syndrome

A simple, one-pot procedure for the preparation of 3H and 14C labelled mono and diesters of fatty acids with 3-phenylamino-1,2-propanediol, compounds shown to have a strong association with Toxic Oil Syndrome, is reported. Ring opening of glycidol with carbon-14 aniline in methanol led to the regioselective insertion of the phenylamino moiety at C-3. This intermediate was allowed to react with the appropriate molar equivalents of tritiated linoleic acid in the presence of DCC and DMAP to give the desired compounds in satisfactory overall yields. © 1998 John Wiley & Sons, Ltd.

Synthesis of tritium and carbon-14 labelled linoleic acid esters of 3-phenylamino-1,2-propanediol, compounds potentially involved in the etiology of the Toxic Oil Syndrome

A simple, one-pot procedure for the preparation of 3H and 14C labelled mono and diesters of fatty acids with 3-phenylamino-1,2-propanediol, compounds shown to have a strong association with Toxic Oil Syndrome, is reported. Ring opening of glycidol with carbon-14 aniline in methanol led to the regioselective insertion of the phenylamino moiety at C-3. This intermediate was allowed to react with the appropriate molar equivalents of tritiated linoleic acid in the presence of DCC and DMAP to give the desired compounds in satisfactory overall yields. © 1998 John Wiley & Sons, Ltd.

Inhibition of cytarabine-induced MDR1 (P-glycoprotein) gene activation in human tumor cells by fatty acid-polyethylene glycol-fatty acid diesters, novel inhibitors of P-glycoprotein function.

Fatty acid ester surfactants Cremophor EL and Solutol HS 15 were described earlier as modulators of multidrug resistance mediated by MDR1 P-glycoprotein (Pgp). We have shown that the most active components of these polydisperse surfactants are fatty acid-polyethylene glycol-fatty acid diesters (FA-PEG-FA). A new generation of Pgp-surfactant inhibitors of defined structure was therefore synthesized. In the present study we show that these compounds are also able to inhibit up-regulation of MDR1 gene expression caused by cytarabine (ARA-C) and doxorubicin in human tumor cell lines H9 and KB 3-1, which express minimal levels of MDR1 mRNA. The surfactant inhibitors, however, had no effect on the induction of MDR1 gene expression by protein kinase C agonists. Using a set of FA-PEG-FA diesters with various fatty acids and different lengths of the PEG domain, we demonstrated that the activity of diester preparations as inhibitors of drug-induced MDR1 activation was in proportion to their activity as inhibitors of Pgp function. Oleic and stearic acid diesters with PEG 900 (20 ethylene oxide units) were the most potent. The poloxamer analogs of these diesters demonstrated similar effects. In contrast, the well-known, structurally unrelated inhibitors of Pgp activity, verapamil, cyclosporin A and PSC 833, had no inhibitory effect on drug-induced MDR1 activation. The ability of FA-PEG-FA diesters to inhibit both Pgp function and drug-induced MDR1 activation suggests that these chemomodulators may be uniquely useful for the prophylaxis of Pgp-mediated multidrug resistance in drug-treated tumors.

Transdermal administration of emedastine.

Transdermal administration of emedastine was tested in vitro and in vivo. In the diffusion cell method in vitro, emedastine free base was more permeable by transdermal administration than emedastine difumarate. Emedastine had higher permeability in hydrophobic vehicles than in hydrophilic vehicles, and was most permeable in fatty acid monoesters. It was suggested that the change in permeability of emedastine from these vehicles was dependent on the change in its partition from the vehicle to the skin. In studies using rabbits in vivo, emedastine had high permeability from fatty acid monoesters and fatty acid diesters as found in in vitro studies, and bioavailability of the drug after transdermal administration was greater than that after peroral administration. The flux of emedastine in vitro was correlative with the pharmacokinetic parameters in vivo. Consequently, it is clear that transdermal permeability of emedastine is very high and that the drug may be efficacious in the system after administration by these means.

Enhancement of polyether biodegradation in activated sludge following exposure to conditioning agents

Abstract Activated sludge exposed to C18 unsaturated fatty acid diesters of polyethylene glycol (PEG) acquires the ability to degrade PEG of average molecular weight (Afn) 1,000, 1,450, 3,350 but not 8,000. Likewise, a polypropylene glycol (PPG) diester of oleic acid enhances the degradation of PPG Afn 1,025. An analogous enhancement in PEG degradative activity is effected by pre‐exposure to polyoxyethylene oleyl monoether. Enhancement of degradation is restricted to polyethers which are the same kind as used in the pretreatment; for example, samples pre‐exposed to PEG unsaturated diester are unable to degrade PPG. Thin layer chromatographic analysis of PEG incubations indicates disappearance of PEGs from the supernatant without a noticeable change in the molecular weight of remaining PEGs. Removal of these compounds from the supernatants occurs well before catabolic CO2 evolution is completed. Since there were negligible increases in the biomass and acetylesterase activity resulting from the catabolism o...

Estrogen induction of alcohol dehydrogenase in the uropygial gland of mallard ducks

Treatment of mallard ducks with estradiol, or a combination of estradiol and thyroxine, has been shown to result in the proliferation of peroxisomes and production of diesters of 3-hydroxy fatty acids, the female pheromones, in the uropygial gland of male and female mallard ducks. Such a treatment results in the induction of a unique set of proteins. A cDNA library enriched in hormone-induced transcripts was subjected to differential screening. The nucleotide sequence of one of the two unique cDNA clones, DGH1, had high similarity to the Human class I alcohol dehydrogenase (ADH) gamma subunit and represented the carboxy-terminus of the protein from amino acid 190-374. SDS/PAGE and Western blot analysis of the proteins indicated that the level of a 38-kDa protein that cross-reacted with antibodies prepared against the chicken ADH was increased 5-7-fold by hormone treatment. Assays for ADH activity in the uropygial gland extracts of male mallards showed a 5-7-fold induction of the enzyme by hormone treatment. The 1.9-kb ADH mRNA levels were increased 12-14-fold under these conditions. Of all the tissues tested, the uropygial gland had the highest levels of ADH mRNA. Induction of ADH by estradiol treatment occurred only in this tissue. Elevated levels of ADH were also observed in the glands of male mallards in eclipse, the post-nuptial condition when the hormonal balance is shifted to higher estrogen levels, suggesting that this enzyme is regulated by estrogens in this period. Estradiol treatment caused an 80% decrease in the NAD+/NADH ratio in the uropygial gland and a twofold increase in the fatty alcohol oxidation rate catalyzed by the gland extract. These observations could help explain how increased levels of ADH could contribute to the production of the diesters.

Estradiol induces proliferation of peroxisome-like microbodies and the production of 3-hydroxy fatty acid diesters, the female pheromones, in the uropygial glands of male and female mallards

During the mating season the female mallards produce sex pheromones, diesters of 3-hydroxy fatty acids, in their uropygial glands. Subcellular fractionation by sucrose and Nycodenz density gradient centrifugations and electron microscopic examination of the fractions showed that diesters of 3-hydroxy acids and the enzymes that catalyze the formation and esterification of the 3-hydroxy fatty acids are located in the catalase-containing fractions, probably peroxisomes, whereas monoester synthesizing activities are located in the endoplasmic reticulum. Fatty acyl-CoA reductase that would provide fatty alcohol needed for the synthesis of monoester and diester waxes was found both in the peroxisomal and endoplasmic reticulum fraction. Upon daily intramuscular injection of estradiol into the females in the nonmating season, the short chain monoester waxes of the uropygial glands were replaced by long chain monoester waxes, and subsequently the monoester waxes were replaced by diester waxes. Injection of thyroxine with estradiol hastened the induction of the compositional changes including diester synthesis. Similar changes, including the synthesis of the female pheromones, were induced in the uropygial glands by the hormone treatment of males that do not normally produce diesters at any time during their life cycle. The structure and composition of the diesters induced by hormone treatment of both males and females were identical to those of the female pheromones produced during their mating season. Electron microscopic examination of diaminobenzidine-treated glands showed that peroxisomes proliferated in the gland of the females in the mating season and in the estradiol-treated males that produce the diesters.

Determination of Sucrose Esters of Fatty Acids by High Performance Liquid Chromatography

A sensitive method was developed for the quantitative determination of sucrose mono-and di-fatty acid esters (SuE) in foods by high performance liquid chromatography (HPLC). The SuE were extracted with tetrahydrofuran from foods and purified by silica gel column chromatography. The isolated SuE were derivatized with 3, 5-dinitrobenzoyl chloride (DNBC) and the reaction products were dissolved in a mixture of tetrahydrofuran and acetonitrile (1:1). A portion of this solution was injected into an Inertsil C8 column and eluted with a linear gradient elution system from 15% water in acetonitrile to 100% acetonitrile over 30min, then hold for 20min.Each SuE was detected with a UV detector set at 230nm. SuE in various kinds of foods could be selectively detected without interference on the HPLC. All peaks of mono-and diesters having C12, C14, C16, C18 C16-C16, C16-C18 and C18-C18 carbon chains could be well separated. The recoveries of SuE added to margarine, ice cream, cookies, curry roux and coffee whitener were more than 80% for the monoesters and more than 75% for the diesters. The detection limit was 0.001% for each SuE.

Separation of carotenol fatty acid esters by high-performance liquid chromatography

Employing isocratic and gradient-elution high-performance liquid chromatography HPLC a number of straight-chain fatty acid esters (decanoate, laurate, myristate, palmitate) of violaxanthin, auroxanthin, lutein, zeaxanthin, isozeaxanthin, and β-cryptoxanthin, prepared by partial synthesis, have been separated on a C 18 reversed-phase column. Several chromatographic conditions were developed that separated a mixture of di-fatty acid esters (dimyristate, myristate palmitate mixed ester, dipalmitate) of violaxanthin, auroxanthin, lutein, and zeaxanthin in a single chromatographic run. Hydroxycarotenoids such as lutein, zeaxanthin, and isozeaxanthin that are not easily separated by HPLC on C 18 reversed-phase columns, can be readily separated after derivatization with fatty acids and chromatography of their esters. Chromatographic conditions for optimum separation of carotenoids from various classes are discussed.

Diesters of 3-hydroxy fatty acids produced by the uropygial glands of female mallards uniquely during the mating season

The uropygial gland secretions produced by female mallards (Anas platyrhynchos) throughout the year were analyzed by thin-layer chromatography and combined gas-liquid chromatography and mass spectrometry. Most of the year, the secretion was composed of wax esters. With the beginning of the mating season in the middle of March, a polar component appeared which became the dominant and sole component of the secretion through April and May and as the mating season ended in June, wax esters became the sole component of the secretion. The polar components were identified to be diesters of n-C8, n-C10, and n-C12 3-hydroxy acids with n-C16 and n-C18 alcohols and n-C6 to C16 even chain acids. Immediately after the diester-producing period the female uropygial glands produced very long chain wax esters composed of fatty acids longer than C12. By the end of August, shorter chain wax esters composed of C6 and C12 acids became the dominant components of the secretion and this composition, previously considered characteristic of mallards, remained constant until March. The observed disappearance of the short chain waxes during the postnuptial period is similar to that in males. The dramatic changes in the composition of the uropygial glands similar to those observed in the female mallards during the mating season have not yet been observed in any other species.

Phosphatidic acid may stimulate membrane receptors mediating adenylate cyclase inhibition and phospholipid breakdown in 3T3 fibroblasts.

Incubation of 3T3 fibroblasts with phosphatidic acid (PA) from egg lecithin or with thrombin resulted in decreases in cellular cAMP due to inhibition of adenylate cyclase, in rapid increases in inositol 1,4,5-tris-,1,4-bis-, and 1-monophosphates probably due to activation of phospholipase C, and in arachidonic acid release. Synthetic PAs consisting of unsaturated fatty acid diesters were as effective as PA from egg lecithin, whereas PAs with saturated fatty acids were only slightly effective and antagonized the effect of active PAs selectively, despite the fact that both types of PA analogues (sodium salts) were apparently dissolved in the incubation medium. PA-induced decreases in cAMP were not affected by omission of Ca2+ from incubation medium but were abolished by prior exposure of cells to islet-activating protein (pertussis toxin). This islet-activating protein treatment of cells was without effect on PA- or thrombin-induced generation of inositol phosphates. Thus, PA-induced inhibition of adenylate cyclase was (but activation of phospholipase C was not) mediated by an islet-activating protein substrate GTP-binding protein. Homologous desensitization was observed with thrombin-, bradykinin-, and PA-induced decreases in cAMP in 3T3 cells; prior exposure of the cells to any one of these agents abolished or greatly diminished the subsequent response to the same agent but did not affect the responses to others. The effects of PA were cell-specific; it failed to decrease cAMP in rabbit platelets in which labeled PA rapidly increasing in response to thrombin or A23187 was mostly outside the cells. Based on these results, it is proposed that PA interacts with its own specific membrane receptors, thereby triggering multiple effector systems in 3T3 cells.

Preparation and emulsifying properties of polyethylene glycol (15OO) diesters of fatty acids

AbstractOil soluble polyethylene glycol (PEG‐1500) diesters of stearic, 12‐hydroxystearic, oleic and 12‐hydroxy oleic (ricinoleic) acids were prepared by standard condensation reaction procedure. The surface active/emulsifying properties of the products were evaluated by determining interfacial tension and through performance test in making water‐in‐oil emulsion. The presence of double bond or hydroxyl group in the C18 acids, PEG content of reacting mixture, and nature and concentration of the catalyst in preparing the emulsifier all were found to have great bearing on the emulsifying property and stability of w/o emulsions, particularly when the aqueous phase contained a significant quantity of ions. Only the first factor, the effect of double bond and/or the hydroxyl group, is discussed in this paper.

HPLC of fatty acid esters of mono‐ and polyhydric alcohols. Part 1: Analytical separation

AbstractThis paper shows how simply and yet very rapidly fatty acid esters of monohydric alcohols, but particularly partial and full fatty acid esters of fully hydric alcohols can be separated and determined by means of high‐pressure liquid chromatography on LiChrosorb RP‐8 with methanol/water. We have separated quantitatively the methylesters of the fatty acids C8:0 to C22:0 and C24:0, the i‐propyl‐, i‐butyl‐, n‐hexyl‐ and i‐octyl‐esters of the even‐numbered fatty acids C8:0 to C18:0, mono‐ and difatty acid esters of the 1,3‐bis‐(2‐hydroxyethyl)‐5,5‐dimethyl‐hydantoin, mono‐, di‐ and triesters of the trimethylolpropane as well as the tetraesters of the penta‐erythrite.

Diesters of alkane diols and 2-hydroxy fatty acids: Identification and discrimination of isomers with the aid of NMR spectroscopy

High resolution nuclear magnetic resonance spectroscopy has been shown to be extremely useful for the identification and discrimination of naturally occurring diesters of 1,2- and 2,3-alkanediols as well as for fatty alkyl esters of acylated 2-hydroxy fatty acids. A comparison of 220 MHz spectra of 1,2 and erythro- 2,3-alkanediol diesters exhibits the following distinguishing features: (1) two non-equivalent methylene protons from the glycol group of 1,2-alkanediol diesters resonate at 3.87 ppm and 4.17 ppm respectively while these resonances are completely absent in the spectrum of 2,3-isomer; (2) methylene protons adjacent to ester carbonyl groups appear as two overlapping triplets at 2.22 ppm in 1,2-alkanediol diesters while the corresponding protons in the 2,3-isomer are displayed as two partially overlapping triplets centered at 2.15 ppm and 2.2 ppm respectively; and (3) methyl protons adjacent to glycol group in 2,3-isomer appear as downfield doublet at 1.13 ppm; this downfield doublet is not shown by 1,2-alkanediol diesters. Erythro- and threo-2,3-alkanediol diesters have also been distinguished from each other; two α-methylenes in erythro isomers appear as partially overlapping triplets while these protons in threo isomer display an apparent quartet centered at 2.22 ppm. Fatty alkyl esters of acylated 2-hydroxy fatty acids display a triplet at 4.79 for 2-position methylene proton, a distinguishing feature not shown by diacyl alkanediols. A distinction between diester lipids and other classes of neutral lipids has also been achieved by the study of nuclear magnetic resonance spectra, particularly in the region of 3–6 ppm.

Studies of the Pyrolysis of Triglycerides

Abstract The pyrolysis of triglycerides (trilaurin and tripalmitin) in an atmosphere of nitrogen at 300–700°C has been attempted. Fatty acids, acrolein, ketones, and olefins have been identified as pyrolysis products. As intermediates of the pyrolysis, unsaturated glycol difatty acid esters and acid anhydrides were also detected. These results suggest a reaction mechanism of the pyrolysis involving the above compounds.