Synthesis of trisubstituted C18 pyrrole fatty ester derivatives

Reaction of methyl 10(11)-dicarbethoxymethyl-9,12-dioxooctadecanoate (1a,1b) with ammonium acetate furnished a mixture of positional isomers of a pyrrole derivative, methyl 9,12-imino-10(11)-dicarbethoxymethyl-9,11-octadecadienoate (2a,2b). Decarboxylation of the mixture of compounds 2a,2b with sodium carbonate in aqueous methanol yielded a mixture of compounds 3a,3b containing a CH₂COOCH₃ group at the 3- or 4-position of the pyrrole ring after esterification. Heating of the hydrolyzed mixture of compounds 3a,3b at 180°C for 1 h gave the desired trisubstituted pyrrole derivatives, methyl 9,12-imino-10(11)-methyl-9,11-octadecadienoate (4a,4b), containing a methyl group at the 3- or 4-position of the pyrrole nucleus. The structures of the products and intermediates were confirmed by infrared, and by¹H and¹³C nuclear magnetic resonance spectroscopy.     

Ultrasound in lipid chemistry,cyclopropanation of unsaturated fatty esters and triglycerides

Concomitant ultrasonic irradiation during the Simmons-Smith reaction facilitated the cyclopropanation of ethylenic fatty esters and triglycerides. Methyl ricinoleate furnished predominantly the corresponding hydroxy cyclopropanoid ester when the reaction was carried out at 85–95 C under ultrasound in the presence of zinc, while a C₁₈ furanoid fatty ester gave a novel tricyclo derivative (methyl 9,12-epoxy-9,10;11,12-dimethanooctadecanoate).     

Ring location in cyclopropane fatty acid esters by boron trifluoride-catalyzed methoxylation followed by mass spectroscopy

Methyl esters of methylcis- andtrans-9,10-methyleneoctadecanoic acids react with 50% boron trifluoride-methanol to produce unsaturated and methoxy-esters; both products are shown by gas chromatography to be a mixture of several isomers. Mass spectra of the methoxylated esters are characterized by intense peaks due to cleavage adjacent to methoxy-functions which allow the position of the ring in the original cyclopropane ester to be easily assigned. Methyl oleate is also partially attacked by 50% BF₃−MeOH to produce a mixture of methyl 9- and 10-methoxyoctadecanoates. 14% BF₃−MeOH does not react with cyclopropane and olefinic esters under the reaction conditions employed.     

Synthesis of phenyl substituted C18 furanoid fatty esters

Methyl 9,12-epoxy-10-phenyl-9,11-octadecadienoate was prepared by acid catalyzed cyclization of methyl 9,12-dioxo-10-phenyloctadecanoate, which was derived from the oxidation of methyl 9-hydroxy-12-oxo-10-phenyloctadecanoate. The latter was exclusively obtained from methylcis-9,10-epoxy-12-oxooctadecanoate with phenyllithium in the presence of copper (I) bromide. A mixture of positional isomers, methyl 9,12-epoxy-10(11)-phenyl-9,11-octadecadienoates, was also prepared by another route. The spectroscopic properties of the various intermediates and products were studied. The positional isomers of the phenyl substituted furanoid fatty esters were characterized by¹³C nuclear magnetic resonance spectrometry.     

Epoxidation reactions of unsaturated fatty esters with potassium peroxomonosulfate

Epoxidation of the double bond in methyl oleate, octadec-11E-en-9-ynoate, ricinoleate (12-hydroxy-octadec-9Z-enoate), iso-ricinoleate (9-hydroxy-octadec-12Z-enoate), and 12-oxo-octadec-9Z-enoate with potassium peroxomonosulfate (oxone, 2 KHSO₅.K₂SO₄) in the presence of trifluoroacetone or methyl pyruvate gave the corresponding monoepoxy derivatives. Reaction of Oxone^® with methyl linoleate and octadeca-9Z,11E-dienoate furnished the corresponding diepoxystearate derivative. Methyl 9,12-dioxo-octadec-10Z-enoate was obtained when a C₁₈ furanoid fatty ester (methyl 9,12-epoxy-9,11-octadecadienoate) was treated with Oxone^®. The yield of these reactions was very high (85–99%), and the epoxy derivatives were readily isolated by solvent extraction. The products were identified by spectroscopic methods.     

Chemical and enzymatic preparation of acylglycerols containing C18 furanoid fatty acids

C₁₈ furanoid triacylglycerol [glycerol tri-(9,12-epoxy-9,11-octadecadienoate)] was prepared by chemical transformation of triricinolein isolated from castor oil. The procedure involved oxidation, epoxidation and cyclization of the epoxy-keto intermediate with sodium azide and ammonium chloride in aqueous ethanol. The furanoid triacylglycerol was also obtained by esterification of C₁₈ furanoid fatty acid with glycerol using Novozyme 435 (Novo Nordisk A.S., Bagsvaerd, Denmark) as biocatalyst. When Lipozyme (Novo Nordisk A.S.) was used, a mixture of the furanoid 1(3)-rac-monoacylglycerol and 1,3-diacylglycerol was obtained. In order to obtain the C₁₈ furanoid 1,2(2,3)-diacylglycerol, selective hydrolysis of the furanoid triacylglycerol was achieved using procine pancreatic lipase intris(hydroxymethyl) methylamine buffer. Interesterification of triolein with methyl C₁₈ furanoid ester in the presence of Lipozyme showed maximum incorporation of 34% of furanoid fatty acid. Extension of the interesterification to vegetable oils (olive, peanut, sunflower, corn and palm oil) allowed a maximum of 24% furanoid acid incorporation to be achieved.     

Furanoid fatty acids from fish lipids

Fatty acids, recently reported as constitutents of certain fish lipids, were identified to be derivatives of furan (furanoid fish fatty acids). 12,15-Epoxy-13,14-dimethyleicosa-12,14-dienoic acid is predominant among the furan acids and is associated withbis-homologs in regard to chain length. Monomethyl acids, such as 12,15-epoxy-13-methyleicosa-12,14-dienoic, are present in appreciable amounts. The structures were concluded from oxidative degradations, from mass spectrometry of methyl esters of the novel acids and fatty acids derived from them by opening the ring, and from nuclear magnetic resonance, infrared, and Raman spectra. The results from chemical procedures and from spectrometric methods were in aggreement with those obtained with authentic methyl 9,12-epoxyoctadeca-9,11-dienoate. The number of substituents at the furan ring greatly influences hydrogenation, hydrogenolysis, and hydrolysis reactions of the ring. Scientific Journal Series 9154, Agricultural Experiment Station, University of Minnesota, St. Paul, MN 55101; Hormel Institute Publication No. 749.     

A study of the structures and reactions of some methyl substituted unsaturated C18 ester intermediates in the synthesis of a racemic mixture of 10-methyloctadecanoic acid

Methyl 10-undecenoate was hydrated to methyl 10-hydroxyundecanoate using mercury (II) acetate in aqueous tetrahydrofuran (THF). Chromic acid oxidation of methyl 10-hydroxyundecanoate gave methyl 10-oxoundecanoate, which was hydrolyzed to 10-oxoundecanoic acid. Reaction of n-octyl magnesium bromide complex in THF with 10-oxoundecanoic acid furnished 10-hydroxy-10-methyloctadecanoic acid after hydrolysis. The latter compound was esterified, and dehydration of methyl 10-hydroxy-10-methyloctadecanoate withp-toluenesulfonic acid in benzene gave a mixture of unsaturated branched fatty ester intermediates:viz. methyl 10-methyl-9-octadecenoate, 10-methyl-10-octadecenoate and 10-octyl-10-undecenoate. Treatment of the mixture of unsaturated branched fatty ester intermediates with mercury (II) acetate in methanol gave exclusively methyl 10-methoxy-10-methyloctadecanoate. Epoxidation of the same mixture of unsaturated fatty esters withm-chloroperbenzoic acid provided a mixture of epoxy derivatives: methyl 9,10-epoxy-10-methyloctadecanoate, 10,11-epoxy-10-methyloctadecanoate and 2-octyl-oxirane-nonanoate. Catalytic hydrogenation of the mixture of unsaturated fatty esters gave a racemic mixture of methyl 10-methyloctadecanoate, which was hydrolyzed to 10-methyloctadecanoic acid. The structures of the mixture of unsaturated branched fatty ester intermediates and their derivatives were characterized by chemical and spectroscopic analyses.     

An efficient ultrasound-assisted zinc reduction of fatty esters containing conjugated enynol and conjugated enynone systems

Reduction of methyl 8-hydroxy-11-E/Z-octadecen-9-ynoate (1) with zinc in either aqueous n-propanol or water under concomitant ultrasound irradiation furnished a mixture of methyl 8-hydroxy-9Z,11E-octadecadienoate (3a) and methyl 8-hydroxy-9Z, 11Z-octadecadienoate (3b) (96% yield). Reduction of methyl 8-oxo-11-E/Z-octadecen-9-ynoate (2) under similar conditions gave methyl 8-oxo-10-Z-octadecenoate exclusively (4, 70%). The latter compound was epoxidized and converted to a C₁₈ furanoid fatty ester (6, methyl 8,11-epoxy-8,10-octadecadienoate) in 70% yield.     

Selective hydroformylation of polyunsaturated fats with a rhodium-triphenylphosphine catalyst

Soybean, safflower and linseed oils and their methyl esters were effectively hydroformylated with a rhodium and triphenylphosphine catalyst system. The product from safflower methyl esters, hydroformylated at 100 C and 1000 psi synthesis gas (H₂ + CO), proved to be a mixture of formylstearate, formyloleate and diformylstearate. At 150 C and 15 00 psi synthesis gas the formyloleate was hydrogenated and the product formed was a mixture of mono- and diformylstearates. The unsaturated monoformyl fraction (100 C) was tentatively identified as a mixture consisting mainly of methyl 9(10)-formyl-cis-12-and methyl 12(13)-formyl-cis-9-octadecenoates. The saturated monoformyl fraction (150 C) was a more complex isomeric mixture of methyl formylstearate. The diformyl fractions from hydroformylated safflower and linseed esters were identified as mixtures consisting mainly of 9,12-(10,13)- and 10,12-(11,13)-diformyloctadecanoates. When hydroformlyation of polyunsaturated fats was interrupted,cis-unsaturated formyl oils resulted. Presented at AOCS Meeting, Houston, May 1971. Northern Marketing and Nutrition Research Division, ARS, USDA.     

Fatty acids: Part 25.1 chemical transformations of C18 furanoid fatty esters

Synthetic and natural C₁₈ furanoid fatty esters were successfully converted to the corresponding furanoid alcohols, aldehydes, halides, ethers, acetates, mesylates, and chain extended by two carbon atoms in high yield to the corresponding C₂₀ furanoid ester homologues. Acid hydrolysis of the furanoid esters furnished dioxostearate derivatives, which were cyclized with ammonium carbonate or ammonia in titanium chloride and with phosphorus pentasulfide to pyrrole and thiophene ester derivatives, respectively. For Part 24, see reference 1.     

Autoxidation of the furan fatty acid ester, methyl 9,12-epoxyoctadeca-9,11-dienoate

The objective of this study was to identify autoxidation products of methyl 9,12-epoxyoctadeca-9,11-dienoate (F_9,12). Previous work has shown that F_9,12 is a product both of autoxidation and singlet oxygen oxidation of the methyl ester derivative of conjugated linoleic acid (CLA). F_9,12, 95% pure, was synthesized from methyl ricinoleate. The synthetic F_9,12 was heated at 50°C in sealed tubes containing air. Each tube contained 6 mg F_9,12 and 1 mg methyl stearate as an internal standard. Samples were taken at 4.5, 7, 23, 46.5, 69.5, and 93 h. The oxidized F_9,12 was dissolved in isooctane and analyzed by gas chromatography (GC), GC-direct deposition-Fourier transform infrared spectroscopy, and GC-electron ionization mass spectrometry. CLA methyl ester was oxidized in a similar manner. Under these conditions, the half-lives of CLA and F_9,12 were 40 and 35 h, respectively. Oxidation products of F_9,12 that were identified included: 5-hexyl-2-furaldehyde (I), methyl 8-oxooctanoate (II), methyl 13-oxo-9,12-epoxytrideca-9,11-dienoate (III), methyl 8-oxo-9,12-epoxy-9,11-octadecadienoate (IV), and methyl 13-oxo-9,12-epoxy-9,11-octadecadienoate (V).     

Reaction of mono-epoxidized conjugated linoleic acid ester with boron trifluoride etherate complex

The reaction of methyl 11, 12-E-epoxy-9Z-octadecenoate (1) with boron trifluoride etherate furnished a mixture of methyl 12-oxo-10E-octadecenoate (3a) and methyl 11-oxo-9E-octadecenoate (3b) in 66% yield. Methyl 9, 10-Z-epoxy-11 E-octadecenoate (2) with boron trifluoride etherate furnished a mixture of methyl 9-oxo-10 E-octadecenoate (4a, 45%) and methyl 10-oxo-11 E-octadecenoate (4b, 19%). A plausible mechanism is proposed for these reactions, which involves the attack on the epoxy ring system by BF₃, followed by deprotonation, oxo formation, and double bond migration to give a mixture of two positional α,β-unsaturated C₁₈ enone ester derivatives (3a/3b, 4a/4b). The structures of these C₁₈ enone ester derivatives (3a/3b, 4a/4b) were identified by a combination of NMR spectroscopic and mass spectrometric analyses.     

Hydrogen sulfide adducts of methyltrans,trans- 9,11-octadecadienoate

Hydrogen sulfide was added to methyltrans, trans- 9,11-octadecadienoate in benzene solution at 25 C with ultraviolet radiation. GC-MS and GLC analysis of the reaction product showed the presence of methyl oleate, methyl stearate, geometric isomers of methyl 9,11-octadecadienoate, methyl 9,12-epoxy-octadeca-9, 11-dienoate, an unknown compound with an apparent molecular weight of 306, methyl 8-(2′,5′-hexylthienyl) octanoate, an unidentified sul-fur ] containing C₁₈ ester with an apparent molecular weight of 326, methyl 9,12-epithiostearate, an adduct of methyltrans,trans- 9,11-octadecadienoate and ben-zene [bicyclo (4.4.0)-deca-2,5,7-triene-l-(Ω-carboxy-methyl heptyl)-4 hexyl] and a probable mixture of methyl 9,11-epidithiostearate, methyl 9,12-epidithio-stearate, and methyl 10,12-epidithiostearate.     

Synthesis of tetrahydrofuran ring containing oligoethylene glycol ethers from the seed oil of Vernonia anthelmintica

A tetrahydrofuran ring containing oligoethylene glycol ethers has been synthesized from the seed oil of Vernonia anthelmintica. The seed oil was reacted with mono-, di-, and triethylene glycols in the presence of boron trifluoride etherate, followed by saponification and esterification (MeOH/H⁺). The oligoethylene glycol ethers thus obtained were epoxidized with perbenzoic acid. The 9,10-epoxy oligoethylene glycol ethers so formed were intramolecularly cyclized in dry benzene using boron trifluoride etherate as a catalyst to yield the tetrahydrofuran ring containing oligoethylene glycol ethers; methyl 9,12-epoxy, 10-hydroxy-13-[2-hydroxyethyl-1-oxy]; methyl 9,12-epoxy,10-hydroxy-13-[2-hydroxy-3-oxapentyl-1-oxy] and methyl 9,12-epoxy,10-hydroxy-13-[8-hydroxy-3,6-dioxaoctyl-1-oxy]octadecanoates, respectively.     

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.     

Omega-formylalkanoates by ozonization of unsaturated fatty esters

Ozonization of the methyl esters of 11-eicosenoic, linoleic, erucic and linolenic acids gave a number of different homologous methyl ω-formylalkanoates. Complete ozonization of the monounsaturated esters formed C₁₁ and C₁₃ compounds with 90% conversion; partial ozonization of the polyunsaturated esters gave C₁₂ and C₁₅ products with maximum conversions at ca. 75% consumption of fatty ester. Thus, methyl linoleate gave 52 and 23% conversions to the 9- and 12-carbon products, and methyl linolenate gave 29, 27 and 19% conversions to the 9-, 12- and 15-carbon products. Yields of aldehyde or acetal esters in distilled products were 70–90% in preparative-scale experiments. Kinetic analysis showed that ozone attack was essentially random. Methanol was used as a participating solvent. Presented in part at the AOCS Meeting, New Orleans, 1962. A laboratory of the No. Util. Res. & Dev. Div., ARS, USDA.     

Analysis of furanoid esters in soybean oil and the effect of variety and environment on furanoid ester content

An improved method was developed to analyze the major furanoid esters in soybean oil. The method is based on urea fractionation of the methyl esters, silver ion chromatography, and gas chromatography of the furanoid concentrate. Activation of the soybean lipoxygenase decreased the amount of furanoid ester recovered from the oil, but the degumming of crude soybean oil and the choice of solvent used to extract soybean lipids caused no change in furanoid ester content. Fifty-six soybean varieties, representing a wide range in maturity group and geographical origin, were grown in Puerto Rico and used to determine the range of furanoid ester contents. Furanoid ester II ranged from 0.033–0.29 mg/g, and ester III ranged from 0.058–0.27 mg/g. The two major furanoid esters were positively correlated with each other and with maturity group. Growth environment as well as variety caused significant differences in furanoid content. Journal Paper No.J-17180 of the Iowa Agriculture and Home Economics Experiment Station, Ames, IA, 50011, Project No. 3414.     

Synthesis of dimethyl-substituted C18 furanoid fatty ester

Reaction of a C₁₈ furanoic fatty acid with dimethyl dicarboxylate (DMAD) furnished the corresponding bicyclo Diels-Alder adduct, which was partially hydrogenated over Pd/BaSO₄. Heat treatment (160–180°C) of the partially hydrogenated product caused a retro-Diels-Alder reaction to yield a furanoid fatty acid derivative containing methoxycarbonyl (COOCH₃) substituents at the 3-and 4-positions of the furan nucleus. Reduction of the COOCH₃ substituents with LiBH₄ gave the corresponding CH₂OH-substituted furanoid fatty acid. Hydrogenation of the latter over Pd/C furnished the desired dimethyl-substituted furanoid acid derivative (overall yield 60%). The spectroscopic properties of the intermediates and product are reported.     

Synthesis of methyl 9,12-epoxyoctadecanoate from castor oil

We report here the synthesis of methyl 9,12-epoxyoctadecanoate (2-[7-methoxycarbonyl-heptyl]-5-hexanyl-tetrahydrofuran). Methyl ricinoleate (methyl 12-hydroxy-9-cis-octadecenoate), isolated from castor oil methyl esters was isomerized with diphenyl disulfide as radical initiator under ultraviolet radiation to give thetrans isomer, methyl ricinelaidate. The latter was cyclized by slow addition of 10% bromine solution in dichloromethane to give methyl 10-bromo-9,12-epoxyoctadecanoate, which on hydrogenation with Pd/C catalyst gave the title compound, methyl 9,12-epoxyoctadecanoate.