Convenient and efficient syntheses of 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal

Lipid peroxidation products 4-hydroxy-2(E)-nonenal (HNE) and 4-oxo-2(E)-nonenal (ONE) were conveniently synthesized using Wittig and Horner-Wardsworth-Emmons (HWE) reaction. Wittig or HWE reaction between an easily prepared phosphorane or phosphonate with glyoxal dimethyl acetal gave a protected 4-oxo-2(E)-nonenal. Hydrolysis gave 4-oxo-2(E)-nonenal, whereas reduction followed by hydrolysis gave 4-hydroxy-2(E)-nonenal.     

The effect of intermittent and continuous heating of soybean oil at frying temperature on the formation of 4-hydroxy-2-trans-nonenal and other α-, β-unsaturated hydroxyaldehydes

4-Hydroxy-2-trans-nonenal (HNE) is a cytotoxic secondary lipid peroxidation product of linoleic acid. Previous investigations in this laboratory showed that HNE is formed in thermally oxidized soybean oil, which is high in linoleic acid. Continuous exposure of the oil to frying temperature (185°C) for up to 6 h graduallyincreased the formation of HNE and other polar lipophilic aldehydes. Additional investigations in this laboratory showed that HNE is absorbed into food fried in thermally oxidized oil in the same concentration as was found in the oil. In the present experiment, the effect of intermittent heating on the formation of HNE in soybean oil was compared with continuous heating. Soybean oil samples were heated either for 1 h each day for five sequential days or for 5 h continuously at 185±5°C. The thermally oxidized soybean oil samples were analyzed by HPLC for the presence of HNE and three other polar lipophilic α-,β-unsaturated hydroxyaldehydes: 4-hydroxy-2-trans-hexanal, 4-hydroxy-2-trans-octenal, and 4-hydroxy-2-trans-decenal. Under intermittent and continuous heating over a total of 5 h, the concentration of these compounds increased similarly. These results indicate that the formation of HNE and other hydroxyaldehydes at frying temperature is a cumulative result of oxidation of PUFA over time.     

2-trans-nonenal,the hardened flavor present in hydrogenated peanut oil

Oils belonging to linoleic-oleic acid group may have a characteristic hardening flavor after hardening and refining. This flavor was isolated from hardened peanut oil by degassing and preparative gaschromatography. An investigation into the structure of this flavor showed it to be 2-trans-nonenal. The structure was confirmed by comparison with an authentic synthesized product. 10-Octadecenoic and 11-octadecenoic acid which are formed during the hardening process (isomerization) of linoleic and oleic acids, are proposed as precursors of the hardening flavor. Presented at the ISF-AOCS World Congress, Chicago, 1970.     

Stereochemistry of Electrophilic Reactions of 4-t-Butyl-1-phenylcyclohexyllithium, -sodium, -potassium and -cesium

The first three title compounds were prepared by treating the diastereomeric 4-t-butyl-1-phenyl-1-phenylthiocyclohexanes 8 or 9 (Scheme 3) with lithium, sodium, or potassium naphthalenide, respectively. The potassium derivative was also obtained by treatment of 9 with sodium/potassium alloy and the cesium derivative was similarly obtained by reaction with cesium/potassium/sodium alloy. Quenching of any of these salts with D₂O gave cis- and trans-4-t-butyl-1-phenylcyclohexane-1-d(cis- and trans- 7 -d) in an approximately 1:1 ratio. The reaction was stereoconvergent and the product ratio independent of the metal; the result is explained in terms of a diffusion controlled reaction of a planar or near-planar carbanion. In contrast, methylation with methyl iodide gave the product of axial methylation 10 in an approximately 2:1 predominance over diastereomer 11 . This result is explained in terms of Curtin-Hammett kinetics involving a stereoelectronically preferred axial approach to the electrophile. ¹³C NMR spectral studies of the lithium, potassium, and cesium salts indicate extensive delocalization of the anionic charge into the ring—somewhat more so with the K and Cs than with the Li salt. This finding supports the hypothesis that at least the K and Cs salts involve a planar carbanion moiety, whereas the Li salt may be slightly nonplanar. Both spectrally and stereochemically, the title compounds differ substantially from the earlier studied 2-phenyl-1,3-dithianes.     

Dehydration of 2-(2-Arylethyl)-2-hydroxy-4-oxopentanoic Acids and their hydrazones to form heterocycles

Dehydration of 2-(2-arylethyl)-2-hydroxy-4-oxopentanoic acids 1 with hydrochloric acid/acetic acid, affords 3-(2-arylethyl)-5-hydroxy-5-methyl-2(5H)-furanones 4 . Compounds of type 1 and 4 represent suitable precursors for the formation of pyridazin-3-ones 7 as they smoothly react with hydrazine. A new series of s-triazolo[4,3-b]pyridazin-3-ones 12 and tetrazolo[1,5-b]pyridazines 15 are obtained from the 3-chloropyridazines 11 upon treatment with semicarbazide and sodium azide, respectively. Reaction of 11 with phenyl- acetyl-hydrazine provides 3-benzyl-6-phenyl-8-(2-phenyl-ethyl)-s-triazolo[4,3-b]pyridazine 13 via dehydrative cyclization of the intermediate 14 which was clarified to exhibit tautomeric equilibria between enol–hydrazine form A and keto–hydrazine form B by means of ¹H and ¹³C NMR spectroscopy. Attempts to synthesize 3-alloxy-pyridazines 18 by reacting 11 with sodium alloxide afford N-allyl compounds 17 .     

Effect of 4-hydroxy-2(E)-nonenal on soybean lipoxygenase-1

The oxidation of linoleic acid by soybean lipoxygenase-1 (LOX-1) was inhibited in a time-dependent manner by 4-hydroxy-2-(E)-nonenal (HNE). Kinetic analysis indicated the effect was due to slow-binding inhibition conforming to an affinity labeling mechanism-based inhibition. After 25 min of preincubation of LOX-1 with and without HNE, Lineweaver-Burk reciprocal plots indicated mixed noncompetitive/competitive inhibition. Low concentrations of HNE influenced the electron paramagnetic resonance (EPR) signal of 13(S)-hydroperoxy-9(Z), 11(E)-octadecadienoic acid (13-HPODE)-generated Fe³⁺-LOX-1 slightly, but higher concentrations completely eliminated the EPR signal indicating an active site hindered from access by 13-HPODE. HNE may compete for the active site of LOX-1 because its precursor, 4-hydroperoxy-(2E)-nonenal, is a product of LOX-1 oxidation of (3Z)-nonenal. Also, it was an attractive hypothesis to suggest that HNE may disrupt the active site by forming a Michael adduct with one or more of the three histidines that ligate the iron active site of LOX-1.     

1-Octen-3-ol and its relation to other oxidative cleavage products from esters of linoleic acid

By means of preparative GLC, 1-octen-3-ol and 2-trans-heptenal could be isolated from mildly oxidized linoleic acid ester and from oils containing this acid (e.g., soybean oil). A hypothesis for the origin of these two substances in natural products is given. The absence of 2-trans-octenal in the cleavage products from methyl linoleate, its presence in oils and the controversial experimental results obtained by various investigators, seem to be reconcilable by assuming the formation of an acetal. The suggested acetal may, on intermolecular cyclic rearrangement and cleavage, give 1-octen-3-ol. *** DIRECT SUPPORT *** A03O2190 00002     

A facile synthesis of 4-hydroxy-2(E)-nonenal

A facile, efficient synthesis of 4-hydroxy-2(E)-nonenal is presented as an alternative to the approaches published previously, which either employed four to six separate steps or furnished low yields. The commercially available 3(Z)-nonenol was sequentially oxidized into 3,4-epoxynonanol by 3-chloroperoxybenzoic acid followed by oxidation of the alcohol by periodinane to afford 4-hydroxy-2(E)-nonenal by this two-step procedure in 48±7% yield.     

Components of the hardening flavor present in hardened linseed oil and soybean oil

The characteristic hardening flavor which develops in hardened linseed and soybean oils during storage has been coned from hardened linseed oil by stripping with nitrogen. After separating the volatile substances by adsorption chromatography on silica, the fraction containing the hardening flavor has been converted into 2,4-dinitrophenylhydrazones (DNPHs) and separated by means of partition chromatography. On regeneration of the fractions of DNPSs obtained, the characteristic hardening flavor was observed in one specific band. Both by hydrogenation and by oxidation of the free carbonyl the carrier of the flavor was found to be an unsaturated aldehyde; however, not of the α-β unsaturated type. Further separation of the regenerated carbonyls by means of gas-liquid chromatography (GLC) points to a C₉-aldehyde. After synthesis of the 4-,5- and 6-cis- andtrans-nonenals, comparison made it probable that the carrier of the hardening flavor is a mixture of 6-cis and 6-trans-nonenal, the latter of which has the greatest share in the hardening flavor. In order to confirm the location of the double bond in the carrier of the hardening flavor a recent isolation technique was applied. The volatile substances from hardened linseed oil were first separated via GLC. After conversion of the carbonyls in question into their DNPHs, the latter have been separated by means of thin-layer chromatography (TLC). By means of IR-analysis and oxidation with osmium tetroxide of the pure derivative, the principal carrier of the hardening flavor has been identified as 6-trans-nonenal.     

H2SO4-SiO2催化7-羟基-4-甲基香豆素的无溶剂合成

分别制备了4种H₂SO₄-SiO₂。以H₂SO₄-SiO₂为催化剂,乙酰乙酸乙酯和间苯二酚为原料,通过Pechmann反应,在无溶剂条件下,催化合成了7-羟基-4-甲基香豆素。以4种不同H₂SO₄-SiO₂、催化剂用量、反应时间、反应温度和反应原料的物质的量比设计了五因素四水平的正交试验,得到负载硫酸催化反应的最佳条件：n(H₂SO₄)∶n(Si)=0.75∶1,n(间苯二酚)∶n(乙酰乙酸乙酯)=1∶1,催化剂用量0.35 g（间苯二酚0.04 mol）,反应时间95 min,反应温度105 ℃,最佳条件下产品收率为72.4%。     

Preparation and properties of new surfactants containingd-glucosamine as the building block

Three types of new surfactants were prepared by usingN-acetyl-d-glucosamine as a starting material. The first type of surfactant, sodium methyl 4,6-O-alkylidene-2-(carboxyl-atomethylamino)-2-deoxy-d-glucopyranoside, was prepared successively by the following treatments: methyl glucosidation ofN-acetyl-d-glucosamine, transacetalization with an appropriate aldehyde dimethyl acetal, deacetylation, and finally reaction of the resulting methyl-4,6-O-alkylidene-2-amino-2-deoxy-d-glucopyranoside (2-amino precursor) with bromoacetic acid. The reaction of this 2-amino precursor with methyl iodide yielded the second type of surfactant, methyl 4,6-O-alkylidene-2-deoxy-2-(trimethylammonio)-d-glucopyranoside iodide, in excellent yield. The last type of compound, sodium methyl 2-acetamide-4,6-O-alkylidene-3-O-[1-(carboxylato)-ethyl]-2-deoxy-d-glucopyranoside, was synthesized by the reaction of methyl 2-acetamide-4,6-O-alkylidene-2-deoxy-d-glucopyranoside with 2-chloropropionic acid. Concerning the two carboxylate types of surfactants, the compounds containing a C₉ or C₁₁ hydrophobic chain in the alkylidene part showed higher water solubility than the corresponding compounds containing a C₇ hydrophobic chain. Both the micelle-forming property and the ability to lower the surface tension of these carboxylate types of compounds increased with an increase in the length of the hydrophobic chain in the alkylidene part. These compounds can be applied to new acid-decomposable types of cleavable surfactants because they contain an acetal group. The acetal bond of the ammonium type of compound was cleaved more slowly than that of the corresponding carboxylate types of surfactants in 2% aqueous HCI solution. The biodegradabilities of these compounds were also determined.     

Ethylene adduct of conjugated octadecadienoic acids: I. Peracid oxidation products

8-(4-n-Hexylcyclohex-2-enyl)octanoic acid obtained by the addition of ethylene totrans,trans-9,11-octadecadienoic acid was treated with 28% hydrogen peroxide in acetic or formic acid to give the hydroxyacetoxy or-formoxy derivative. Saponification of the hydroxyacetoxy derivative yielded two crystalline glycols. The hydroxyformoxy fatty acid was converted in one step either to the glycol ester, methyl 8-(4-n-hexyl-2,3-dihydroxycyclohexyl)octanoate, by reaction with anhydrous hydrochloric acid in methanol or to the acetone derivative of the glycol ester by treatment with dimethoxypropane and anhydrous hydrochloric acid in methanol. Epoxidation of the C₂₀ cyclohexene fatty methyl ester gave the oxirane derivative. A ring opening reaction of the diol acid with periodic acid yielded 9,12-diformylstearic acid. Presented in part at the AOCS-AACC Meeting, Washington, D.C., April 1968. No. Utiliz. Res. Dev. Div., ARS, USDA.     

Conformational behavior of 3,3-dimethyl-3-silathiane 1-oxide and its diastereomeric 2-methyl derivatives

The conformational behavior of 3,3-dimethyl-3-silathiane 1-oxide 3 and its trans-4 and cis-4 2-methyl derivatives has been studied by ¹H and ¹³C NMR. The equatorial conformer 3-eq for 3 and the diequatorial isomer trans-4-eq for trans-4 predominate (>95%) in CDCl₃ solution. In contrast, the cis-4-ax conformer is the more preferred form of cis-4. The conformational free energy (ΔG°) in the equilibrium cis-4-ax???cis-4-eq was determined to be about +0.01 and +0.52?kcal?mol^?1 at 26 and ?120°C, respectively. The Gibbs free energy of activation (ΔG ^?) for the inversion cis-4-ax?→?cis-4-eq was estimated to be 8.1?kcal?mol^?1 at ?100°C.     

Synthesis and characterization of copolyesters based on tartaric acid derivatives

A series of aliphatic copolyesters based on naturally occurring l-tartaric acid amenable to facile post-polymer modification have been synthesized and characterized. The hydroxyl groups of the tartaric acid were protected and copolyesters were synthesized by taking different feed molar ratio of dimethyl 2,3-O-isopropylidene tartarate and dimethyl succinate with 1,6-hexanediol. Then, a series of copolyesters were synthesized by taking equal feed molar ratio of dimethyl 2,3-O-isopropylidene tartrate and dimethyl succinate or dimethyl adipate with different alkane diols. The acetal protecting groups were then selectively hydrolyzed to prepare a new series of copolyesters with pendant hydroxyl groups along the copolymer chain. The number average molecular weights (M _n) of the copolymers were found to vary in the range of 3.7–8.4 × 10³ g mol⁻¹. The hydroxy copolyesters show higher glass transition (T _g) and melting (T _m) temperatures as compared to isopropylidene copolyesters and the T _g varies from −8.0 to −48.2 °C depending on the feed ratio of the comonomers. The hydrolytic degradation studies of copolyesters revealed that hydroxyl copolyesters degrade faster than isopropylidene copolyesters.     

Facile and general method for preparation of (E)-4-hydroxy-2-alkenals

A facile one-pot synthesis of (E)-4-hydroxy-2-alkenals such as (E)-4-hydroxy-2-nonenal, (E)-4-hydroxy-2-heptenal, and (E)-4-hydroxy-2-hexenal was achieved from the corresponding (2E,4E)-2,4-alkadienals by reduction-oxygenation with molecular oxygen and triethylsilane in the presence of cobalt(II) porphyrin as a catalyst followed by treatment with trimethylphosphite.     

Structural significance of the alkyl substituent at the C-4 of (+)-trans-verbenyl acetate in sex pheromonal activity of the American cockroach

The significance of the alkyl group at the C-4 of (+)-trans-verbenyl acetate, which is the sex pheromone mimic of the American cockroach, was investigated. Seven alcohols possessing an ethyl, propyl, or dimethyl group at this position of the 6,6-dimethylbicyclo[3.1.1]heptane skeleton were synthesized and evaluated by behavioral assay. All of the alcohols were inactive, while three of four acetates of the 2-alcohols induced sexual behavior in male cockroaches at the 0.02 or 0.5 mg dosage level, either of which is many orders of magnitude higher than the threshold level of the natural sex pheromones (10^–8 mg). Among the acetates, the compounds with a methyl group or an -oriented ethyl group at C-4 showed the highest activity. The results are discussed in terms of spatial requirements of the molecules for interactions with the receptor.Studies on the sex pheromone mimic of the American cockroach, (+)-trans-verbenyl acetate. Part VIII. For Part VII, seeComp. Biochem. Physiol.,70A: 229–234 (1981).     

2-trans,4-cis,7-cis-Decatrienal,the fishy off-flavor occurring in strongly autoxidized oils containing linolenic acid or ω 3,6,9, etc., fatty acids

A possible decomposition product of oils containing unsaturated fatty acids with the double bond pattern ω3,6,9 or ω3,6,9, etc., is 2-trans,4-cis,7-cis-decatrienal. It has therefore been investigated whether this trienal is present in strongly autoxidized linolenic acid, soybean, linseed and fish oils. Via a degassing technique the carbonyls from the samples of oils heated in a closed system under nitrogen were collected and separated as their 2,4-dinitrophenylhydrazones (DNPHs) by thin layer chromatography (TLC). The presence of 2-trans,4-cis,7-cis-decatrienal in the samples was positively established by TLC, UV absorption and mass spectroscopy of its DNPH. All analytical data established the complete identity of the isolated DNPH with a synthesized 2,4,7-decatrienal-DNPH. The free aldehyde obtained on hydrolysis of the alkatrienal-DNPH in question had the same flavor as authentic 2-trans,4-cis,7-cis-decatrienal, having a fish or rather a whale oil flavor.     

Synthesis of Calix[4]arene-Based Thiourea Derivatives for Extraction of Toxic Dichromate and Arsenate Ions

In the environment, the presence of toxic oxyanions such as Cr(VI) and As(V), especially in drinking water, creates serious hazards to human health. For efficient and selective detection of these species; novel calix[4]arene-based thiourea derivatives which obtained using p-tert-butylcalix[4]arene as starting material have been prepared from m-aniline or o-aniline or o-aminophenol in moderate yield. The structures of all new synthesized compounds obtained from these reactions were determined by using FTIR, ¹H, and ¹³C NMR spectroscopy. The complexing properties of calix[4]arene-based thiourea derivatives have been studied towards the As(V) and Cr(VI). It was found that calix[4]arene-based thiourea derivative 5,11,17,23-tetra-tert-butyl-25,27-bis(o-amino-phenylthioureido propoxy)-26,28-hydroxycalix[4]arene is an effective extractant for carrying HCr₂O₇^2? anions.     

A CO2-switchable amidine monomer: synthesis and characterization

Smart system employed CO₂ gas as new trigger has been attracting enormous attention in recent years, but few monomers that are capable of switching their hydrophobicity/hydrophility upon CO₂ stimulation have been reported. A novel CO₂ responsive monomer, 4-vinylbenzyl amidine, is designed and synthesized in this work with N,N-dimethylacetamide dimethyl acetal and 4-vinylbenzyl amine that is prepared through the Gabriel reaction. In bi-phase solvent of n-hexane and water, the monomer dissolves in n-hexane first and then transforms into water upon the CO₂ treatment, indicating a hydrophobic to hydrophilic transition. This transformation is demonstrated as reversible by monitoring the conductivity variation of its wet dimethyl formamide solution during alternate bubbling/removing CO₂. The protonation of 4-vinylbenzyl amidine upon CO₂ treatment is demonstrated by ¹H NMR which also accounts for the dissolubility change. The reversible addition-fragmentation chain-transfer polymerization of this monomer is also performed, finding the reaction only occurs in glacial acetic acid. The reason can be ascribed to the different radical structure produced in different solvent.     

Synthesis of octadecynoic acids and [1-14C] labeled isomers of octadecenoic acids

Geometric and positional isomers of [1-¹⁴C] octadecenoic acids have been synthesized by modifications of published procedures. Positional isomers of octadecynoic acids also have been synthesized to obtain the geometric and positional isomers of the unlabeled octadecenoic acid analogs. The syntheses were accomplished by coupling a haloalkyl compound with a substituted acetylene using n-butyl lithium in hexamethylphosphoramide. The coupled product, either a 17-or 18-carbon acetylenic alcohol, could be semihydrogenated and chain extended to afford a carboxy labeled derivative, could be partially hydrogenated and chain extended to afford a carboxyl labeledcis-ortrans-octadecenoic acid in the former case. In the latter case, octadecynoic,cis-octadecenoic ortrans-octadecenoic acids could be obtained by the appropriate reactions. The methods used in this study enabled the synthesis of¹⁴C-labeled fatty acids in generally higher yields and by simpler reactions than were previously possible.