Synthesis and antimicrobial activity of fatty 2-morpholinones prepared from epoxy fatty acid methyl esters

Reactions of methyl 10,11-epoxyundecanoate (I), methyl 9,10-epoxyoctadecanoate (II) methyl 12,13-epoxy-cis-9-octadecenoate (III) and methyltrans-2,3-epoxyhexadecenoate (IV) with glycine in dimethylformamide (DMF) in the presence of anhydrous AlCl₃ as catalyst have yielded 5(6)-[8′-carbomethoxyoctyl]-2-morpholinone (V); 5(6)-[7′'-carbomethoxyheptyl]-6(5)-octyl-2-morpholinone (VI);5(6)-[10′-carbomethoxydec-cis-2-enyl)-6(5)-pentyl-2-morpholinone (VII), and 5-tridecyl-6-carbomethoxy 2-morpholinone (VIII), respectively in excellent yield. The products have been characterized with the help of spectral data and microanalysis. Antifungal and antibacterial screening of (V–VIII) showed pronounced activity against four bacteria and seven fungal species. Presented in part at the 43rd Annual Convention of the Oil Technologists' Association of India (OTAI) held in Bombay, India In February 1988.     

Synthesis of 2, 3 fatty aziridines

A new route for the synthesis of 2,3-aziridines is described. The reaction of methyl 2,3-dibromohexadecanoate (II) with ammonia at 0 C gave methyl 2-bromohexadec-2-enoate (III, ca. 93%). Compound III, on further treatment with ammonia at 25 C, gave methyl 2-aminohexadec-2-enoate (IV, ca. 5%), methyltrans-2,3-epiminohexadecanoate (V, ca. 64%), methylcis-2,3-epiminohexadecanoate (VI, ca 24%) andtrans-2,3-epiminohexadecamide (VII, ca 3%). The structures were established with the help of elemental analyses and infrared (IR), nuclear magnetic resonance (NMR) and mass spectral analyses.     

Reaction of methyltrans-2,3-epoxyhexadecanoate with urea: Synthesis of long chain fatty 2-oxazolidones

Methyltrans-2,3-epoxyhexadecanoate on refluxing with urea in dimethylformamide (DMF) afforded isomeric 4(5)-tridecyl-5(4)-carbomethoxy-cis-2-oxazolidone (II), 5-tridecylmethylene hydantoin (II) and 2-hydroxy-3-carbamidohexadecanoic acid (III). Presented at the 4th Convention of the Indian Council of Chemists at Uttar Pradesh, India, December 1984.     

Lasioderma chemistry sex pheromone of cigarette beetle (Lasioderma serricorne F.)

A chemical study of the sex pheromone of the cigarette beetle was carried out. Seven components were isolated from active fractions of column chromatography of the female extract, and their structures were elucidated by spectroscopic evidence and confirmed by synthesis to be (4S,6S,7S)-4,6-di-methyl-7-hydroxynonan-3-one (serricornin) (I), 2,6-diethyl-3,5-dimethyl-3,4-dihydro-2H-pyran (anhydroserricornin) (II), 4,6-dimethylnonan-3,7-dione (III), 4,6-dimethylnonan-3,7-diol (IV), 4,6-dimethyl-7-hydroxy-4-nonen-3-one (V), (2S,3R)-2,3-dihydro-3,5-dimethyl-2-ethyl-6-(l-methyl-2-oxobutyl)-4H-pyran-4-one (serricorone) (VI) and (2S,3R)-2,3-dihydro-3,5-dimethyl-2-ethyl-6-(1-methyl-2-hydroxybutyl)-4H-pyran-4-one (serricorole) (VII).These structural features suggested that the occurrence of these components might be related to the polyketide biosynthesis. The behavioral bioassay and BAG experiments revealed the biological role of each component in the copulatory behavior of this insect.     

Preparation and characterization of derivatives of isoricinoleic acid and their antimicrobial activity

Methylisoricinoleate (methyl-9-hydroxy-cis-12-octadecenoate) (I) has been derivatized to yield new fatty acid derivatives analogous to those obtained from the ricinoleic acid of castor oil. These derivatives include 1,9-dihydroxy-12-octadecene (II); 1,9-diacetoxy-12-octadecene (III); 12,13-epoxy-1,9-diacetoxyoctadecane (IV); 9-cyanoethoxy-1-hydroxy-12-octadecene (V); 1-morpholine-9-hydroxy-12-octadecene (VI), and 1-morpholine-9-cyanoethoxy-12-octadecene (VII). Structures of these compounds were established by chemical and spectral data. The compounds V, VI and VII showed antifungal activity againstAlternaria sp.,Helminthosporium sp.,Penicillium citrinum, Fusarium oxysporum, Aspergillus ochraceous, A. flavus, A. niger, Actinomyces sp. andCladosporium harbarum.     

Reaction of methyltrans-2,3-epoxyoctadecanoate with phenyl isocyanate: Synthesis of fatty 3-phenyl-2-oxazolidones

Reaction of methyltrans-2,3-epoxyoctadecanoate (I) with phenyl isocyanate in dimethylformamide (DMF) in the presence of anhydrous AlCl₃ as catalyst has yielded 3-phenyl-4-pentadecylmethyleneoxazolid-2,5-dione (II) and 4(5)-carbomethoxy-5 (4)-pentadecyl-3-phenyl-cis-2-oxazolidone (III). The products have been characterized with the help of spectral data and microanalyses. Presented at the 41st Annual Convention and Symposium of the Oil Technologists’ Association of India (OTAI) in Hyderabad in February, 1986.     

Iodoazide addition to olefinic esters and their reaction with methanolic KOH

Addition of iodine azide to methyl 10-undecenoate (1), methyl oleate/elaidate (III,IV) and methyltrans-2-hexadecenoate (VII) yielded methyl 10-azido-11-iodoundecanoate (II, ∼ 100%), methylerythro/threo-9(10)-azido-10(9)-iodooctadecanoate (V,VI) and methylerythro-3-azido-2-iodohexadecanoate (VIII), respectively. The reaction of iodoazide adduct (II) with methanolic KOH yielded 10-azidoundec-10-enic acid (IX) and 10-oxoundecanic acid (X), while V and VI gave a mixture of 9(10)-oxooctadecanoic acid (XI). Adduct VIII, under the identical condition after esterification, gave 3 products, methyl 4-methoxy-trans-2-hexadecenoate (XII), 2-oxopentadecane (XIII) and methyl 3-methoxyhexadecanoate (XIV). The unusual behavior of VIII can be tentatively attributed to the role of adjacent carbonyl on the expected elimination of HI by methanolic alkali.     

Synthesis of substituted fatty oxathiolanes and thioethers from an allylic oxo fatty acid ester

Substituted oxathiolane and thioether derivatives have been synthesized from an allylic oxo fatty acid ester. The reaction of methyl 4-oxo-trans-2-octadecenoate with 3-mercaptopropan-1,2-diol (1-thioglycerol) affords methyl 4-(3′-hydroxymethyl-1′,4′-oxathiolane)-2(3)-(O-mercaptopropan-1″,2″-diol)-octadecanoate (II), methyl 4-oxo-2(3)-(O-mercaptopropan-1′,2′-diol)-octadecanoate (III), methyl 4-(3′-hydroxy-l′,5′-oxathiane)-2 (3)-(S-mercaptopropan-1″,2″-diol)-octadecanoate (IV), methyl 4-oxo-2(3)-(S-mercaptopropan-1′, 2′diol)-octadecanoate (V) and methyl 4-(3′-hydroxymethyl-1′, 4′-oxathiolane)-2(3)-(S-mercaptopropan-1″, 2″-diol)-octadecanoate (VI). Structures of the individual reaction products have been established on the basis of spectral data and microanalyses.     

Synthesis and characterization of copolymers with alternating 1,4-bis(5'-acetyl-2'-thienyl)benzene or 1,3-bis(5'-acetyl-2'-thienyl)benzene chromophore and disiloxane units

Summary Activated (Ph₃P)₃RuH₂CO (Ru) catalyzed copolymerization of 1,4-bis(5'-acetyl-2'-thienyl)benzene (I) and 1,3-divinyltetramethyldisiloxane (II) yields alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,4-benzene)-3',3"-bis (thiophenylene)] (III). On the other hand, Ru catalyzed copolymerization of 1,3-bis(5'-acetyl-2'-thienyl)benzene (IV) and II fails. Nevertheless, Ru catalyzed reaction of IV with excess vinylpentamethyldisiloxane (V) yields 1,3-bis(4'-pentamethyldisiloxy-ethyl-5'-acetyl-2'-thienyl)benzene (VI). VI undergoes acid catalyzed siloxane equilibration polymerization to give alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,3-benzene)-3',3"-bis(thiophenylene)] (VII) and hexamethyldisiloxane. Copolymers III and VII have been characterized. Received: 26 July 1999/Revised version: 12 October 1999/Accepted: 12 October 1999     

Synthesis of tetrazole from α, β—Unsaturated carbonyl fatty acid

Methyl 4-oxo-trans-2-octadecenoate (II), when treated with excess hydrazoic acid in the presence of BF₃-etherate, produced 66% methyl 5-aza-nonadec-trans-2-enoate (4,5-d)-tetrazole (III), 10% methyl 5-aza-nonadec-4-oxo-trans-2-enoate (IV) and 7% pentadecamide (V). Individual products were characterized by spectral and elemental methods.     

Homolytic decomposition of linoleic acid hydroperoxide: Identification of fatty acid products

An isomeric mixture of linoleic acid hydroperoxides, 13-hydroperoxy-cis-9,trans-11-octadecadienoic acid (79%) and 9-hydroperoxy-cis-12,trans-10-octadecadienoic acid (21%), was decomposed homolytically by Fe(II) in an ethanol-water solution. In one series of experiments, the hydroperoxides were decomposed by catalytic concentrations of Fe(II). The 10⁻⁵ M Fe(III) used to initiate the decomposition was kept reduced as Fe(II) by a high concentration of cysteine added to the reaction in molar excess of the hydroperoxides. Nine different monomeric (no detectable dimeric) fatty acids were identified from the reaction. Analyses of these fatty acids revealed that they were mixtures of positional isomers identified as follows: (I) 13-oxo-trans,trans-(andcis,trans-) 9,11-octadecadienoic and 9-oxo-trans,trans- (andcis,trans-) 10,12-octadecadienoic acids; (II) 13-oxo-trans-9,10-epoxy-trans-11-octadecenoic and 9-oxo-trans-12, 13-epoxy-trans-10-octadecenoic acids; (III) 13-oxo-cis-9,10-epoxy-trans-11-octadecenoic and 9-oxo-cis-12, 13-epoxy-trans-10-octadecenoic acids; (IV) 13-hydroxy-9,11-octadecadienoic and 9-hydroxy-10,12-octadecadienoic acids; (V) 11-hydroxy-trans-12, 13-epoxy-cis-9-octadecenoic and 11-hydroxy-trans-9, 10-epoxy-cis-12-octadecenoic acids; (VI) 11-hydroxy-trans-12, 13-epoxy-trans-9-octadecenoic and 11-hydroxy-trans-9,10-epoxy-trans-12-octadecenoic acids; (VII) 13-oxo-9-hydroxy-trans-10-octadecenoic acids; (VIII) isomeric mixtures of 9, 12, 13-dihydroxyethoxy-trans-10-octadecenoic and 9, 10, 13-dihydroxyethoxy-trans-11-octadecenoic acids; and (IX) 9, 12, 13-trihydroxy-trans-10-octadecenoic and 9, 10, 13-trihydroxy-trans-11-octadecenoic acids. In another experiment, equimolar amounts of Fe(II) and hydroperoxide were reacted in the absence of cysteine. A large proportion of dimeric fatty acids and a smaller amount of monomeric fatty acids resulted. The monomeric fatty acids were examined by gas liquid chromatography-mass spectroscopy. Spectra indicated that the monomers were largely similar to those produced by the Fe(III)-cysteine reaction. Presented in part at the American Chemical Society Meeting, Los Angeles, March 1974. ARS, USDA.     

Thermal alteration of a cyclic fatty acid produced by a flaxseed extract

Methyl 8-[2-(cis-pent-2′-enyl)-3-oxo-cis-cyclopent-4-enyl] octanoate (I) is the methyl ester of a cyclic fatty acid synthesized enzymically from an incubation of linolenic acid with an extract of flaxseed (Linum usitatissimum L.). A proposed trivial name for I is methyl 12-oxo-cis-10, 15-phytodienoate (12-oxo-PDA). The evidence presented indicated that compound I has thecis configuration of the carbon chains with respect to the cyclopentenone ring. Treatment with acid, base, or heat isomerized I to a second product (II) that has thetrans configuration of the carbon chains. Prolonged heat treatment of II yielded a third cyclic product, methyl 12-oxo-9(13),cis-15-phytodienoate (III).     

Synthesis of sulfur-Containing derivatives from olefinic fatty esters

The reaction of 3-mercaptopropan-l,2-diol with methyl 10-undecenoate (Ib) yielded three products, methyl 11-(3′-mercaptopropan-l′,2′-diacetoxy) undecanoate (II, 48.9%), methyl 11-(1-oxapropan-2′-acetoxy-3′-mercaptoacetyl) undecanoate (III, 27.4%) and methyl 10-(3′-mercaptopropan-1′-acetoxy-2′-ol) undecanoate (IV, 23.0%) along with hydrolyzed starting material (Ia, 5.4%). The same reaction with methyl 9-octadecenoate (Vb) gave an isomeric product, 9(10)-(3′-mercaptopropan-l′-acetoxy-2′-ol) octadecanoic acid (VI, 78.5%) and oleic acid (Va, 21.4%). Reaction withtrans-2-octadecenoic acid (VII) afforded 2(3)-(3′-mercaptopropan-l′-acetoxy-2′-ol) octadecanoic acid (VIII, 85.7%).     

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.     

Synthesis of sulfur heterocycles from α,β-unsaturated carbonyl fatty acid esters

Alkyl chain substituted oxathiolanes from allylic oxo are described. Reaction of methyl 4-oxo-trans-2-hexadecenoate (1) with β-mercaptoethanol yields methyl 4-oxathiolane-trans-2-hexadecenoate (II), methyl 4-oxathiolane-2(3)-(S-β-mercaptoethyl acetate) hexadecanoate (III) and methyl 4-oxathiolane-2(3)-(S-β-mercaptoethanol)hexadecanoate (IV).     

Synthesis and antibacterial activity of some new diarylsulphides and diarylsulphones containing azetidin-2-one and/or diazetidin-2-onyl moities

Cyclonucleophilic addition of N-phthaloylaminoacid chlorides (II on 4-(N-ary-lideneamino)-4′-nitrodiphenyl sulphides (I) in dioxane and triethylamine afforded 4-(4″-aryl-3″-phthalylamino-2″-oxo-azetidin-1″-yl)-4′-nitro-diphenyl sulphides (III). Hydrazinolysis of III yielded 4-(4″-aryl-3″-amino-2″-oxo-azetidin-1″-yl)-4′-nitro-diphenyl sulphide hydrochlorides (IV). Condensation of IV with anisaldehyde using ethanol and piperidine as a basic catalyst gave 4-(4″-aryl-3″-anisylidine amino-2″-oxoazetidin-1″-yl)-4′-nitrodiphenylsulphides (V) in good yields. Interaction of V with chloroacetyl chloride in dioxane and triethylamine produced 4-(4″-aryl-3″-substituted β-lactamyl-2″-oxo-azetidin-1″-yi)-4′-nitrodiphenyl sulphides VI. Oxidation of IV, V and VI using hydrogen peroxide/glacial acetic acid mixtures gave the corresponding sulphones (VII), (VIII) and (IX). Sulphones of the type IX were obtained by unequivocal synthesis through interaction of sulphone-anils VIII with chloroacetyl chloride. The antibacterial activities of some of these compounds were determined.     

Odor similarity between stress-inducing odorants in wistar rats

Odor similarity to the odor of 4-mercapto-4-methyl-2-pentanone (I) was measured on eight rats by generalization of a conditioned avoidance response tocis- andtrans-8-mercapto-p-menthan-3-one (II and III), 3-mercapto-3-methyl-2-pentanone (V), andt-amyl mercaptan (VI). Previously, these odorants had been found to induce stress in rats in an open-field situation. In the present experiment, rats generalized the avoidance response learned with I, for V, VI, and to a lesser extenttrans-isomer III, implying odor similarities;cis isomer II was discriminated. Odor similarity between mercapto ketone I and mercaptan VI is surprising since VI lacks the keto group.     

Novel olygomeric C-3 esters of betulin derivatives

Novel copolymers of C-3 esters of betulin derivatives (3-hydroxy-1-cyano-2,3-seco-2-nor-19β,28-epoxyoleane 3-O-vinylbenzoate (I), 3-hydroxy-1-cyano-2,3-seco-2-nor-19β,28-epoxyoleane 3-O-vinylacetate (II), methyl 3-hydroxy-1-cyano-2,3-seco-2-norlup-20(29)-en-28-oate 3-O-vinylbenzoate (III)) with N-vinylpyrrolidone and acrylonitrile have been prepared by free radical copolymerization. Kinetic regularities of the process were investigated. New water-soluble silver nanocomposites based on (III) copolymer with N-vinylpyrrolidone [poly((III)-VP)] have been developed. The average silver particle size ranged from 40 to 52?nm, with the corresponding UV–vis absorption peak position at 400?nm. The nanocomposite obtained has a significant cytotoxic activity toward melanoma cell line and may be considered for the development of new materials for medical applications.     

Stabilization of gamma-irradiated poly(vinyl chloride) by epoxy compounds. I. Radiation yield of hydrogen chloride and changes of epoxy group concentration in gamma-irradiated PVC–stabilizer mixtures

The G_HCl values of γ-irradiated PVC mixtures and the changes of the epoxy group concentration were studied after addition of various amounts of five epoxy stabilizers: diglycidyl ether of 2, 2-bis(4-hydroxy-3-methyl phenyl)propane (I), diglycidyl ether of 2, 2-bis(4-hydroxy-3-nitrophenyl)-propane (II), styrene oxide (1, 2-epoxy ethyl benzene) (IV), epoxidized ricinus oil (VI), and epoxidized soybean oil (Drapex 6.8.) (VII). It is stated that only about 50% of epoxy groups, declining in the system, take part in binding of HCl; the rest of these groups disappear as a consequence of other reactions. In connection with the data of the previous paper,¹ the results presented indicate that the process of stabilization goes in two stages. In the first stage the process consists of the HCl capture by the epoxy groups; in the second stage, due to the remaining part of the stabilizer molecule, a protective effect occurs. This effect consists, for the stabilizers I, II, IV, of gaining the energy by the benzene ring and, for the stabilizers VI, VII, of a mechanical drawing of polymer chains, which makes the energy transfer more difficult. Having the greatest content of epoxy oxygen (about 10%), the styrene oxide (IV) stabilizes best.     

Derivatization of keto fatty acids,Part IX. Synthesis and characterization of oxathiolanes

Oxathiolanes are prepared from the condensation of the oxo fatty acids with β- mercaptoethanol using BF₃etherate as catalyst. 10-Oxoundecanoic acid (I) reacts with the reagent promptly and gives 1-(ethylene oxathiolane) undecanoic acid (V). A similar reaction of 9-oxooctadecanoic acid (II) yields 9-(ethylene oxathiolane) octadecanoic acid (VII). Hemimercaptals (VI, VIII) are also isolated as minor products in the above reactions. Methyl 9,10-dioxooctadecanoate (III) is also found to react readily and affords methyl 9(10)- (ethylene oxathiolane)- 10(9)oxooctadecanoate (IX) as the sole product. There is no reaction with 2-oxooctadecanoic acid (IV). The spectral (infrared, nuclear magnetic resonance, mass) properties of oxathiolanes are detailed.