A novel method for the introduction of a methyl group into the furan ring of a 2,5-disubstituted C18 furanoid fatty estervia a malonic acid function

Furan ring opening with benzohydroxamic acid of methyl 9,12-epoxy-9,11-octadecadienoate gave a mixture of positional isomers of conjugated methyl 3-phenyl-1,4,2-dioxazolyl C₁₈-enone esters 6a,6b. Michael addition of diethyl malonate anion to the conjugated enone system of 6a,6b furnished the corresponding malonyl intermediates 7a,7b, which upon removal of the dioxazole ring by hydrolysis gave methyl 10- and 11-dicarbethoxymethyl-9,12-dioxooctadecanoate 8a,8b. Cyclization of the latter gave the trisubstituted C₁₈ furanoid fatty esters 9a,9b, containing the malonate ester function at the 3-/4-position of the furan ring. Base hydrolysis of compounds 9a,9b gave the corresponding tricarboxylic acid derivatives 10a,10b, which were esterified to the trimethyl esters 11a,11b in BF₃/MeOH. When a mixture of 9a,9b was refluxed with Na₂CO₃/MeOH, hydrolysis of the malonate ester function was followed by decarboxylation to yield a-CH₂COOH substituent at the 3-/4-position of the furan ring (12a, 12b). Esterification of the latter with BF₃/MeOH gave the corresponding methyl diester derivatives 13a,13b. When a mixture of tricarboxylic acids 10a,10b was heated at 160–180°C for 6 hr, exhaustive decarboxylation of malonic acid function furnished a methyl group at the 3-/4-position of the furan nucleus. Esterification of the decarboxylated product gave a mixture of trisubstituted furanoid compounds 14a,14b (overall yield 28%). The procedure constitutes a novel method for the introduction of a methyl groupvia a malonic acid group to the 3-/4-position of the furan ring of a 2,5-disubstituted C₁₈ furanoid fatty ester.     

Cyclic fatty esters: Synthesis and characterization of methyl ω-(6-alkyl-3-cyclohexenyl) alkenoates

Diunsaturated C₁₈ cyclic fatty acid methyl esters of known structure and configuration were synthesized as model derivatives of cyclic fatty acids formed in heat-abused vegetable oils for characterization and further biological evaluation. The Wittig reaction was used to prepare 5 pure methyl esters: (a) 12-(3-cyclohexenyl)-11-dodecenoate, (b) 11-(6-methyl-3-cyclohexenyl)-10-undecenoate, (c) 10-(6-ethyl-3-cyclohexenyl)-9-decenoate, (d) 9-(6-propyl-3-cyclohexenyl)-8-nonenoate and (e) 8-(6-butyl-3-cyclohexenyl)-7-octenoate. Diels-Alder cycloaddition reactions between 1,3-butadiene and appropriate (E)-2-alkenals produced 3-cyclohexenal intermediates. The appropriate methyl ω-bromoesters and their triphenylphosphonium bromides were made and converted to their respective ylids with NaOCH₃ in DMF. The appropriate 3-cyclohexenals and phospho-ylids were reacted, and the desired cyclic ester products were isolated in crude yields of 30–83% as liquids and fractionally distilled. The crude cyclic esters were purified either by preparative TLC or by saponification-esterification. Double bonds in purified cyclic esters weretrans-isomerized and hydrogenated. Each derivative was characterized by IR,¹H-NMR,¹³C-NMR, capillary GLC and GC-MS. On the basis of these analyses, no positional isomers were detected, Z-unsaturated isomers were produced in better than 90% purity, and the alkyl and ester ring substituents were predominantlytrans to each other. Presented in part at the AOCS meeting, New Orleans, LA, May 1981.     

The rearrangement of fatty cyclopropenoids in the presence of boron trifluoride

The destruction of the cyclopropenoid ring system of methyl 9,10 methyleneoctadec-9-enoate (methyl sterculate) with boron trifluoride etherate has been shown to give a complex mixture of products, including methyl esters of C₁₉ allenes (12%), a C₁₈ alkyne (11%) and a variety of C₁₉ and C₂₀ conjugated dienes containing either a methyl or methylene branch. The methylene group lost from the methyl sterculate reactant in the formation of methyl octadec-9-ynoate is incorporated into a second molecule of reactant to yield a mixture of methyl 9-methylene-trans-nonadec-10-enoate and the 11-methylene-trans-9-isomer.     

Comparison of some commercial waxes by gas liquid chromatography

Volatile components (hydrocarbons, monoesters, free acids as methyl esters and free alcohols as acetates) of seven unhydrolyzed commercial waxes-ouricury, carnauba, Chinese insect, lac, esparto, candelilla and Japan wax—have been analyzed and compared by gas liquid chromatography. Though appreciable portions of the waxes were nonvolatile, the results were sufficient to distinguish the seven waxes completely. Methanolysis products were analyzed directly by gas liquid chromatography, and the results agreed with those previously obtained for hydrolysis products of these waxes. Ouricury wax gave 18% C₂₄−C₃₄ αω-diols and 4% C₂₄−C₃₂ ω-hydroxy acids, in addition to 28% C₂₀−C₃₂ aciods and 17% C₂₂−C₃₄ alcohols, on methanolysis. NRCC No. 13387.     

Ethylene adduct of conjugated octadecadienoic acids: III. Aromatization of C20 cyclohexene methyl esters

A procedure is described for the catalytic aromatization of the ethylene adduct of conjugated isomers of methyl octadecadieonate. When the C₂₀ cyclohexene fatty methyl esters were heated at 290–300 C with palladium and 1-octadecene as hydrogen acceptor, C₂₀ aromatic cyclic esters were obtained in 90–95% yield.     

Direct determination of saturated fatty acids in fats,oils, and methyl esters

Summary A direct gravimetric method has been developed for the determination of saturated fatty acids in fats, oils, and methyl esters. The procedure involves methanolysis of the triglycerides to produce methyl esters, followed by oxidation of the unsaturated methyl esters by potassium permanganate. The undesired, acidic oxidation products are removed by alkaline washing and the saturated methyl esters thus isolated are weighed directly. The method is intended for the determination of saturated fatty acids having C₁₆ or longer carbon chains. Small quantities of C₁₄ saturated acids will be included in the determination if present with other higher saturated acids. The method is applicable to both natural and hydrogenated vegetable oils. It is not applicable to oils containing large amounts of C₁₄ and lower saturated acids. Concentrations of saturated acids ranging from 3 to 90% in known glyceride mixtures and from 0.3 to 95% in mixtures of methyl esters were determined with an average difference from the calculated value of 0.8%. Replicate determinations on samples in the 10 to 30% saturates range gave a standard deviation of 0.3 to 0.4%. Presented at the spring meeting, American Oil Chemists’ Society, New Orleans, La., April 28 to May 1, 1957     

Synthesis of oxygenated fatty acid esters from santalbic acid ester

The reaction of methyl octadec-trans-11-en-9-ynoate (1) with mercuric sulfate in the presence or absence of sulfuric acid is described. Treatment of 1 with mercuric sulfate in absolute methanol yielded methyl 9(10)-oxoocta-dec-trans-11-enoates (Product A). This product, upon treatment withm-chloroperbenzoic acid, afforded methyltrans-11,12-epoxy-9-oxooctadecanoate (4) and methyl 10-oxooctadec-trans-11-enoate (2). Sodium borohydride reduction of A furnished the corresponding hydroxy esters. The treatment of 1 with mercuric sulfate in the presence of sulfuric acid gave as major product methyl 9(10)-oxo-11(12)-methoxyoctadecanoates and methyl 9(10)-oxoocta-dec-trans-11-enoates as a minor product. When methyl 11,12-epoxyoctadec-9-ynoate was reacted with acid in methanol, methyl 12-hydroxy-11-methoxyoctadec-9-ynoate was formed, which on treatment with zinc chloride in CCl₄ yielded methyl 9,12-epoxyoctadec-9,11-dienoate exclusively. The preparation of oxo fatty esters from the total methyl esters ofSantalum album was also demonstrated. The structures of the products were established by chemical derivatization and spectral characterization.     

The fatty acids of wax esters and sterol esters from vernix caseosa and from human skin surface lipid

Separation of sterol esters from wax esters in the lipids of vernix caseosa and adult human skin surface was accomplished by column chromatography on MgO. The fatty acids of the sterol esters and wax esters of both samples were separated into saturates and monoenes, and examined in detail by gas liquid chromatography (GLC). The saturated fatty acids of the wax esters of vernix caseosa and of adult human skin surface were remarkably similar. They ranged in chain length from at least C₁₁ to C₃₀, six skeletal types being present: straight even, straight odd, iso, anteiso, other monomethyl branched and dimethyl branched. A large number of patterns of monoenes were observed, each pattern consisting of desaturation of a specific chain at Δ6 or Δ9 plus its extension or degradation products. The mole per cent of the total Δ6 and Δ9 patterns of wax ester fatty acid monoenes of vernix caseosa were 87% and 12%, respectively, and 98% and 1%, respectively, for adult human skin surface lipid. The sterol ester fatty acids of vernix caseosa were much different from those of adult human skin surface: vernix caseosa saturates were largely branched and of lengths greater than C₁₈, whereas the saturates of adult human surface lipid resembled the wax ester fatty acids. Of the vernix caseosa monoene patterns, the mole per cent was 30% Δ6 and 70% Δ9, whereas of the adult human skin surface sterol ester fatty acids 89% were Δ6 and 11% Δ9. Chain extension was particularly pronounced in the sterol ester fatty acid monoenes of vernix caseosa amounting to 7–8 C₂ units in some cases. The fatty acids of the sterol esters of both vernix caseosa and adult human skin surface appear to be derived from the sebaceous gland and from the keratinizing epidermis, but those of the wax esters are from the sebaceous glands only.     

Identification of novel octadecadienoic fatty acids in the seaweedCladophora rupestris through oxidative ozonolysis of the alcohols prepared from the acids

The BF₃−MeOH reagent for ozonolysis of ethylenic unsaturation does not oxidize alcohols. It is therefore feasible to determine the position of ethylenic unsaturation in long chain fatty alcohols of synthetic or natural origin by recovering the methyl ester products intact and silylating the alcohol function of half-ester, half-alcohol, products prior to gas liquid chromatographic analysis. The C₃ fragment from methylene-interrupted alkyl chains is not recovered, but, by first reducing carboxyl ester groups to alcohols, the terminal difunctional products can be identified in nonmethylene-interrupted dienoic fatty acids. The seaweedCladophora rupestris is shown to contain Δ5,Δ11-,Δ8,Δ11-, and Δ11, Δ14- as well as Δ9,Δ12-octadecadienoic acid.     

Organoselenium-mediated cyclization of hydroxyolefinic fatty acids and m-CPBA oxidation of selenium-containing 1,4-epoxy acids

Chlorophenylselenenylation methodology is shown to cause cyclization of naturally occurring β- and γ-hydroxyolefinic acids. The phenylseleno-substituted 1,4-epoxides (tetrahydrofurans) thus obtained are oxidized by m-chloroperbenzoic acid (m-CPBA). Reaction of phenylselenenyl chloride with methyl 12-hydroxyoctadec-cis-9-enoate (methyl ricinoleate) gave methyl 9,12-epoxy-10-phenylselenenyloctadecanoate in useful yields. A similar reaction of phenylselenenyl chloride with methyl 9-hydroxyoctadec-cis-12-enoate afforded a quantitative yield of methyl 9,12-epoxy-13-phenylselenenyloctadecanoate. Oxidation of selenium-containing 1,4-epoxy esters by m-chloroperbenzoic acid (1 equivalent) yielded the respective olefinic 1,4-epoxy esters, while 5 equivalent m-CPBA afforded the corresponding oxirane esters of epoxytetrahydrofurans in high yields. The structure of the individual reaction products have been established from analytical and spectral data and corroborated by a study of their mass spectra.     

Molecular species of wax esters in jaw fat of atlantic bottlenose dolphin,Tursiops truncatus

The jaw fat of the Atlantic bottlenose dolphin (Tursiops truncatus) contains unusual wax esters which can be separated into short chain (<C₂₄) and long chain (>C₂₄) fractions by thin layer chromatography. The short chain wax esters (28 wt. %) have been characterized as a 72∶24∶4 mixture of isovaleroyl, isobutoryl, and 2-methylbutyrol, esters of C₁₄–C₁₈ n- and iso-alcohols. The intact <C₂₄ esters have been resolved into individual molecular species by gas liquid chromatography on open-tubular polyester columns. The long chain wax esters (12 wt. %) contain C₁₀–C₂₂ n- and iso-acids esterified to the same C₁₄–C₁₈ n- and iso-alcohols. Gas liquid chromatography of the intact, hydrogenated >C₂₄ esters on a short JXR column has characterized them according to carbon number and the number of methyl branches they contain.     

Ultrasound-assisted synthesis of santalbic acid and a study of triacylglycerol species inSantalum album (Linn.) seed oil

Methyl ricinoleate (1) was treated with bromine and the dibromo derivative (2) was reacted with ethanolic KOH under ultrasonic irradiation to give 12-hydroxy-octadec-9-ynoic acid upon acidification with dil. HCl. The latter compound was methylated with BF₃/methanol to give methyl 12-hydroxy-octadec-9-ynoate (3). Compound3 was treated with methanesulfonyl chloride in the presence of triethylamine in CH₂Cl₂ to give methyl 12-mesyloxy-octadec-9-ynoate (4). Reaction of methyl 12-mesyloxy-octadec-9-ynoate with aqueous KOH under ultrasonic irradiation (20 kHz) gave (11E)-octadecen-9-ynoic acid (5, santalbic acid, 40%) and (11Z)-octadecen-9-ynoic acid (6, 60%) on acidification with dil. HCl. These isomers were separated by urea fractionation. The¹³C nuclear magnetic resonance (NMR) spectroscopic properties of the methyl ester and the triacylglycerol (TAG) esters of these enynoic fatty acid isomers were studied. The carbon shifts of the unsaturated carbon nuclei of the methyl ester of theE-isomer were unambiguously assigned as 88.547 (C-9), 79.287 (C-10), 109.760 (C-11), and 143.450 (C-12) ppm while the unsaturated carbon shifts of the (Z)-enynoate isomer appeared at 94.277 (C-9), 77.561 (C-10), 109.297 (C-11), and 142.668 (C-12) ppm. In the¹³C NMR spectral analysis of the TAG molecules of type AAA containing either the (Z)-or (E)-enyne fatty acid, the C-1 to C-6 carbon atoms on the α- and β-acyl positions were differentiated. The unsaturated carbon atoms in the α- and β-acyl chains were also resolved into two signals except that of the C-11 olefinic carbon. Sandal (Santalum album) wood seed oil (a source of santalbic acid) was separated by silica chromatography into three fractions. The least polar fraction (7.2 wt%) contained TAG which had a random distribution of saturated and unsaturated fatty acids, of which oleic acid (69%) was the predominant component. The second fraction (3.8 wt%) contained santalbic acid (58%) and oleic acid (28%) together with some other normal fatty acids. Santalbic acid in this fraction was found in both the α- and β-acyl positions of the glycerol “backbone”. The most polar fraction (89 wt%) consisted of TAG containing santalbic acid only. The distribution of the various fatty acids on the glycerol “backbone” was supported by the results from the¹³C NMR spectroscopic analysis.     

Hydroesterification of 1-alkenes in Supercritical Carbon dioxide

The palladium catalysed hydroesterification of linear alkenes to obtain carboxylic esters in supercritical carbon dioxide is studied for the first time. Palladium complexes with phosphines containing –CF₃ groups are used as catalyst precursors. For 1-hexene, conversions into the corresponding methyl esters up to 67% were obtained using [PdCl₂(PhCN)₂]/P(3,5-CF₃C₆H₄)₃.     

A simple method for the preparation of pure 9-d-hydroperoxide of linoleic acid and methyl linoleate based on the positional specificity of lipoxygenase in tomato fruit

Incubation of linoleic acid with crude homogenate of tomato fruit gave a high yield (69%) of linoleic acid hydroperoxides with a ratio of 9- to 13-hydroperoxide isomers of 96∶4. After chromatography of the products, as free acids or methyl esters, hydroperoxides with 9- to 13-isomeric ratios of >99∶1 were obtained. The major product was characterized as 9-d-hydroperoxy-octadeca-trans-10,cis-12-dienoic acid. The results demonstrate the positional specificity of lipoxygenase from tomato fruit.     

Lipase-catalyzed reactions involving thia fatty acids and ester derivatives

Enzymatic hydrolysis of synthetic methyl 5-, 9-, and 12-thiastearates in aqueous media withCandida cyclindracea or porcine pancreatic lipases gave the corresponding fatty acids in 70–100% yield. Hydrolysis of the 3- and 4-positional isomers gave only 15–25% of the free thia fatty acids, suggesting discrimination against these isomers by lipases. No lipolysis was achieved with methyl 2-thialaurate under a range of reaction conditions. Esterification of the 3-, 4-, 5-, 9-, and 12-thiastearic acids withn-butanol inn-hexane using Lipozyme (immobilizedRhizomucor miehei) as the biocatalyst gave the corresponding butyl esters in 80–95% yield. Interesterification (acyl exchange) of triolein with methyl 9-thiastearate in the presence of Lipozyme showed the incorporation of 9-thiastearoyl chain at only one of the α-positions of triolein. In the case of methyl 2-thialaurate, no lipase-catalyzed acyl exchange reaction was possible. This study showed that the position of the sulfur atom in thia fatty esters affects the lipase-catalyzed hydrolysis and interesterification reactions.     

Alkali-isomerized linoleic acid

Summary Alkali-isomerized linoleic acid and its methyl ester have been found to have boiling points higher than the corresponding normal C₁₈ acids and esters. By careful fractional distillation of methyl esters of alkali-isomerized C₁₈ cottonseed acids, methyl linoleate of 95% or more purity is obtained consisting of 75% conjugated methyl linoleate and some 20% of methyl ester of an altered linoleic acid. Paper No. 69, Journal Series, Research Department, General Mills, Inc. (Presented at the 19th Annual Fall Meeting of the American Oil Chemists’ Society, Nov. 7–9, 1945, in Chicago, Ill.)     

Analysis of the dark-colored impurities in sulfonated fatty acid methyl ester

A fractionally distilled C₁₄−C₁₆ fatty acid methyl ester, derived from palm oil, was sulfonated with gaseous SO₃ in a falling film reactor to form an α-sulfo fatty acid methyl ester (α-SF; unbleached and unneutralized form). The included dark-colored impurities were then separated from α-SF as a diethyl ether-insoluble matter. After purification by thin-layer chromatography, the colored species were analyzed by ion-exchange chromatography, gel-permeation chromatography, and nuclear magnetic resonance spectrometry. These data suggested that the colored species were polysulfonated compounds with conjugated double bonds. Minor components in the raw fatty acid methyl ester, found by gas chromatography/mass spectrometry, were spiked into the purified methyl palmitate and then sulfonated. The unsaturated methyl ester and hydroxy ester showed the worst color results. The methyl oleate and methyl 12-hydroxystearate were then sulfonated and analyzed. Deep black products were obtained, which showed the same properties as the colored species in α-SF. It was concluded that low levels of unsaturated fatty acid methyl esters and hydroxy esters in the fatty acid methyl ester are the main causes of the coloring.     

Fatty acid-specific, regiospecific, and stereospecific hydroxylation by cytochrome P450 (CYP152B1) from Sphingomonas paucimobilis: Substrate structure required for α-hydroxylation

Fatty acid α-hydroxylase from Sphingomonas paucimobilis is an unusual cytochrome P450 enzyme that hydroxylates the α-carbon of fatty acids in the presence of H₂O₂. Herein, we describe our investigation concerning the utilization of various substrates and the optical configuration of the α-hydroxyl product using a recombinant form of this enzyme. This enzyme can metabolize saturated fatty acids with carbon chain lengths of more than 10. The K _m value for pentadecanoic acid (C₁₅) was the smallest among the saturated fatty acids tested (C₁₀–C₁₈) and that for myristic acid (C₁₄) showed similar enzyme kinetics to those seen for C₁₅. As shorter or longer carbon chain lengths were used, K _m values increased. The turnover numbers for fatty acids with carbon chain lengths of more than 11 were of the same order of magnitude (10³ min⁻¹), but the turnover number for undecanoic acid (C₁₁) was less. Dicarboxylic fatty acids and methyl myristate were not metabolized, but monomethyl hexadecanedioate and ω-hydroxypalmitic acid were metabolized, though with lower turnover values. Arachidonic acid was a good substrate, comparable to C₁₄ or C₁₅. The metabolite of arachidonic acid was only α-hydroxyarachidonic acid. Alkanes, fatty alcohols, and fatty aldehydes were not utilized as substrates. Analysis of the optical configurations of the α-hydroxylated products demonstrated that the products were S-enantiomers (more than 98% enantiomerically pure). These results suggested that this P450 enzyme is strictly responsible for fatty acids and catalyzes highly stereo- and regioselective hydroxylation, where structure of ω-carbon and carboxyl carbon as well as carbon chain length of fatty acids are important for substrate-enzyme interaction.     

Oxidative cyclization of unsaturated fatty acids with lead tetraacetate

The reaction of 10-undecenoic acid with lead tetraacetate (LTA) in the presence of acetic acid and anhydrous potassium acetate gave a eutectic mixture of 10(11)-acetoxy-11(10)-methylundecanoic acid (25%), 10,11-diacetoxyundecanoic acid (15%) and 5-(ω-carboxyoctyl) γ-butyrolactone (45%). Similar reaction withcis-9-octadecenoic acid yielded a eutectic mixture of 9(10)-acetoxy-10(9)-methyloctadecanoic acid (20%) and 4(5)-(ω-carboxyheptyl)-5-(4)-octyl γ-butyrolactone (40%). In the reaction withtrans-2-enoic acids (C₁₆ and C₁₈) products obtained were: 1,2-diacetoxypenta- and heptadecane (27%), 3-acetoxyhexa- and octadecanoic acid (31%) and 2-(2-penta- and heptadecyl) succinic anhydride (23%), respectively. The structures of individual compounds were characterized by spectral methods.     

Possible fatty acyl pheromone precursors in Spodoptera littoralis. Search for 11- and 12-hydroxytetradecanoic acids in the pheromone gland

Lipidic extracts of Spodoptera littoralis pheromone glands submitted to acid methanolysis using: (i) sulfuric acid/methanol/benzene (0.1∶4∶2, by vol) at 90°C for 1 h; (ii) 12 N HCl/methanol (1∶2; vol/vol) at 90°C for 1 h, or (iii) 14% BF₃-MeOH at 90°C for 1 h did not reveal the presence of either 11- or 12-hydroxytetradecanoic acid in the extracts, as concluded from the gas chromatography-mass spectrometry analyses. Under the above methanolysis conditions, a synthetic sample of methyl (14, 14, 15-²H₃) 12-hydroxytetradecanoate remained unaltered. These results may indicate that formation of (E)-11-tetradecenoic acid from tetradecanoic acid does not occur in the pheromone gland by dehydration of an intermediate hydroxyacid. Acid methanolysis of a lipidic extract using BF₃-MeOH led to the formation of a mixture of methoxy fatty acid methyl esters, identified by gas chromatography-mass spectrometry. These methoxy derivatives should arise from BF₃-catalyzed addition of methanol to the double bond of the natural monounsaturated fatty acyl derivatives present in the gland. Thus, under the same conditions, a synthetic sample of methyl (Z)-11-tetradecenoate was partially transformed into methyl 11-methoxytetradecanoate and methyl 12-methoxytetradecanoate. This reaction might be a useful alternative procedure to obtain methoxy derivatives of olefins, which are very helpful for the structural characterization of the parent alkenes.