Dimer acid structures. The thermal dimer of normal linoleate,methyl 9-cis, 12-cis octadecadienoate

The thermal dimer (290C) of normal methyl linoleate and its hydrogenated form have been examined by mass spectrometry. Parent mass peaks of the hydrogenated dimer show the presence of monocyclic, bicyclic, and tricyclic structures. The monocyclic structure is formed via the conjugation-Diels-Alder mechanism. The bicyclic structure is best explained by an extension of the hydrogen transfer free radical coupling mechanism. The noncyclic dehydrodimer resulting from free radical coupling undergoes a relatively rapid intramolecular cyclization to a bicyclic structure, probably by an interval Diels-Alder reaction. A model noncyclic dehydro-linoleate dimer was shown to give a bicyclic dimer as the predominant structure under thermal dimerization conditions. The tricyclic dimer may result from intramolecular alkylation of the bicyclic structures. Presented at the AOCS Meeting, Philadelphia, October 1966. Journal Series No. 450, General Mills Research Laboratories.     

Untersuchungen über die Struktur dimerer Fettsäuren IV: Struktur dimerer 9c,12c-Octadecadiensäure-methylester

Investigations on the Structure of Dimeric Fatty Acids, Part IV: Structure of Dimeric Methyl-9^c,12^c-octadecadienoates After 65 hrs. of heating methyl-9^c,12^c-linoleate at 280°C under argon, dimers in 24% yield could be isolated, which can be hydrogenated to completeness. Mass spectrometry of the mixture of dimers and those of their hydrogenated products showed that the dimers comprise of saturated tricyclic, monounsaturated bicyclic, diunsaturated monocyclic and triunsaturated acyclic dimers, all having the mol. weight 588, and dehydrodimers having mol. weight 586. Acyclic dehydrodimers with four double bonds could not be detected. Mass spectrometry of the conversion products of the dimers with monoperphthalic acid showed that the dehydrodimers occur predominantly as bicyclic and tricyclic compounds with two double bonds and one double bond respectively. Diels-Alder dimers with tetrasubstituted cyclohexene structure are not formed in the thermal dimerisation of methyl-9,12-linoleate under aforesaid conditions. The possible path of formation of the dimers via radical intermediates is discussed.     

Dimer acid structures. the thermal dimer of methyl 10-trans, 12-trans,linoleate

Thermal dimerization of the conjugated 10-trans, 12-trans linoleate (250C, 5 hr) produced a dimer whose structure is shown to be that of the Diels-Alder reaction between two molecules of monomer, with one molecule acting as diene, and either one of the two double bonds of the second molecule acting as dieneophile. This produces four skeletal isomers of a tetrasubstituted (1,2,3,4) cyclohexene structure with α-β unsaturation on one chain. The isomers formed depend on whether the 10 or the 12 double bond acts as dieneophile, and whether the monomers add “head to head” or “head to tail.” Evidences for the structures include chemical analyses, ozonolysis, nuclear magnetic resonance, IR and UV spectrometry and particularly mass spectrometry of the distilled dimer, of the completely hydrogenated dimer, and of the aromatized dimer formed by catalytic dehydrogenation. The hydrogenated dimer can be separated into two components by TLC. These are probably related to “head to head” vs. “head to tail” addition. Presented at the AOCS Meeting, New Orleans, 1964. Journal Series No. 366.     

Dimer acid structures. The dehydro-dimer from methyl oleate and Di-t-butyl peroxide

The dehydro-dimer of methyl oleate was prepared and its structure determined as a model of a non-ring dimer for reference in studying the structure of other fatty dimer acids. The dehydro-dimer of methyl oleate is formed by the action of di-t-butyl peroxide on methyl oleate. The reaction is stoichiometric; one mole of DTBP producing one mole of dehydrodimer and two moles of t-BuOH, when excess methyl oleate is used. The dimer was shown to contain two double bonds, and to be formed by carbon-to-carbon linkages predominantly and equally at the 8, 9, 10 and 11 carbons of the oleate monomer segments. Unsaturation was determined by quantitative hydrogenation and far UV absorption. The points of linkage were established by diagnosis of the positions of the involved tertiary carbons of the hydrogenated dimer 1) by chemical oxidation, and 2) by mass spectrometry. Positions of the double bonds were determined by quantitative ozonization, reductive cleavage followed by gas chromatography of the aldehydes and aldehyde esters. Precise molecular weight of the hydrogenated dimer was determined from the parant mass peak at the expected m/e of 594, confirming the non-ring structure. The unhydrogenated dimer showed a parent m/e peak at the expected value of 590. The bridging at the 8 and 10 positions is explained as being due to coupling of radicals with limiting resonance structures resulting from loss of a hydrogen atom from the methylene at position 8. The bridging at the 9 and 11 positions is explained as due to coupling of limiting resonance structures resulting from loss of a hydrogen atom from the methylene at position 11. Mass spectrometric data indicate that the dimerization is a coupling of the expected free radical forms, rather than attack by an oleate free radical on the double bond of an intact oleate molecule, with subsequent loss of hydrogen to form the second double bond in the dimer. Coupling at the 2-position (α to COOCH₃) occurs in not more than 5–10% of the molecules. A small amount of cyclic dimer may be present. Journal Series No. 295. Central Research Laboratories, General Mills, Inc., 2010 E. Hennepin Ave., Minneapolis, Minn. Presented at the AOCS meeting in Atlanta, April, 1963.     

Confirmatory mass-spectral data for cyclic fatty acid monomers

Cyclic fatty acid monomers (CFAM) are degradation products found in heat-abused edible oils. This study confirms previously published data and reports the structural elucidation of hydrogenated and deuterated monocyclic and bicyclic CFAM prepared from the corresponding unsaturated species that were previously isolated from heated flaxseed (linseed) oil. CFAM structures were determined as 2-alkyl-4,4-dimethyloxazoline derivatives by using gas chromatography-electron ionization mass spectrometry. The observed retention times for the deuterated CFAM were about 0.1 min shorter than those of the corresponding hydrogenated species. For two minor six-membered ring CFAM components, an increase in the mass of the unsaturated ring by eight mass units upon deuteration indicated the addition of four deuterium atoms to two double bonds in that ring. These data unequivocally confirmed the identity of cyclohexadienyl CFAM species in the original CFAM mixture that was isolated from heated linseed oil. The observed electron ionization mass spectrometic data for minor hydrogenated and deuterated CFAM species, which correspond to the last two eluting monounsaturated species, were consistent with CFAM having bicyclic (fused 5- and 6-membered rings) structures. The location of the ring along the fatty acid chain was also confirmed for all saturated CFAM mixture components. The presence of a pair of deuterium atoms on two adjacent carbon atoms further confirmed the previously determined double-bond position along the fatty acid chain of the corresponding parent (unsaturated) compound. This work was presented in part at the 85th AOCS Annual Meeting in Atlanta, Georgia, May 8–12, 1994.     

松节油催化热异构产物的气相色谱-质谱分析

用气相色谱-质谱联用技术(GC-MS)对Pd/C催化剂上松节油直接催化热异构的反应产物进行了分析鉴定,共分离出46个峰,鉴定出43个化合物,其中主要产物为单环单萜烯苧烯、α-焦烯、1,3,5,5-四甲基-1,3-环己二烯、无环单萜烯3,4-二甲基-2,4,6-辛三烯、2,6-二甲基-2,4,6-辛三烯、双环单萜烯莰烯、单环单萜烃对伞花烃,其相对质量分数分别为:57.87%、2.92%、1.45%、5.59%、7.15%、2.78%、3.39%。分析鉴定结果表明,松节油在Pd/C催化剂上发生开环异构生成单环单萜为主反应,并伴随深度开环异构、分子间氢转移、水合重排等副反应,倍半萜只发生极少量的异构化反应,蒎烯转化率为90.04%,蒎烯可高选择性地开环热异构制备单环单萜苧烯,苧烯选择性为73.17%。     

Characterization of products from clay catalyzed polymerization of tall oil fatty acids

Products obtained by acid clay catalyzed dimerization of oleic, elaidic, and tall oil fatty acids were characterized. The monomeric products (35% of total) consisted of stearic, octadecenoic (66%trans-), and mid chain monomethyl branched acids, both saturated and unsaturated. The polymeric products (65% of total) consisted of linear, alicyclic, aromatic, and polycyclic dimers. The tall oil fatty acid based dimer closely resembled oleic dimer in polycyclic character and linoleic dimer in aromatic and linear structures. Oleic dimers contained the highest linear structural content, while linoleic dimer contained the largest polycyclic content. Alicyclic structures were the principal components of all three products. The monocyclic dimer structures present consisted of six membered ring systems with linoleic and tall oil fatty acid dimers containing the highest aromatic contents. Presented at the National American Chemical Society Meeting, New York, August 1972.     

13C nuclear magnetic resonance spectroscopic analysis of the triacylglycerol composition of some margarines

The triacylglycerol fraction of three samples of margarine, namely “Flora” (Holland), “Kaliakra” (Bulgaria), and “Corona” (Holland), were studied by¹³C nuclear magnetic resonance spectroscopy. By examining the various carbon chemical shifts of the saturated and unsaturated carbon nuclei, “Flora” margarine was shown to contain a mixture of hydrogenated and unhydrogenated vegetable oils. This technique allowed all major acyl groups (saturated, oleate, linoleate, and linolenate) and minor acyl components [different positional isomers of long-chain (E)- and (Z)-monoenoic moieties, arising as by-products during catalytic hydrogenation] to be identified. The amount of each fatty acid present in the margarine was also estimated from the relative intensities of the corresponding signals. “Kaliakra” margarine consisted of a blend of unhydrogenated natural fats and oils that contained saturated fatty acids, oleate, and linoleate. There were no signs in the spectrum of “Kaliakra” of any (E)-isomers, nor signals associated with positional unsaturated acyl groups (other than oleate and linoleate). The sample of “Corona” margarine consisted of a mixture of hydrogenated and unhydrogenated vegetable oils and butter (1.3%). The presence of butter in this sample was identified by the characteristic carbon shifts of the C-1 to C-4 carbon atoms of butyrate. The distribution of the fatty acids on the glycerol “backbone” also was estimated by this technique.     

Thermal reactions of methyl linoleate. I. Heating conditions,isolation techniques,biological studies and chemical changes

Methyl linoleate, diluted with an equal weight of methyl laurate, was heated without exclusion of air at 200C for 200 hours. The reaction mixture was separated by means of molecular distillation, urea adduction, column chromatography, and gas chromatography. Cyclic and aromatic materials were detected in the nonurea adductable monomer fractions. The dimer was separated into polar and nonpolar fractions. Analytical data for the nonpolar dimer are consistent with a cyclic Diels-Alder product. Bioassays showed the nonadductable monomer, the polar dimer, and a fraction of intermediate boiling point to be toxic when administered to weanling male rats. Urea-adductable fractions, nonpolar dimer, and polymer were not toxic. The concentrations of the toxic components were so low that the heated linoleate, before fractionation but after removal of the laurate, was not toxic.     

The deposition of polyunsaturated fatty acids in the rat fed partially hydrogenated vegetable oil

The composition of deposited polyenoic fatty acids in rats fed liquid or partially hydrogenated corn oil was determined by gas chromatography, which did not distinguish isomeric forms, and by lipoxidase which reacted with thecis, cis-methylene-interrupted acids. The two methods gave similar results for the liver fatty acids of rats fed either the unhydrogenated or partially hydrogenated oil. Of the fatty acids from the epididymal fat pads of rats fed the hydrogenated product, an appreciable quantity of linoleate isomers did not react with lipoxidase. The total amount of linoleic acid deposited was related to the total fatty acid pattern of the dietary oil. It appeared that thetrans-acids were mostly metab-olized and that the originalcis,cis-linoleic acid remaining in the partially hydrogenated product was preferentially incorporated into tissues. One of 10 papers to be published from the Symposium “Hydrogenation” presented at the AOCS Meeting, New Orleans, April 1970.     

Chromatographic studies on oxidative and thermal fatty acid dimers

A chromatographic study was carried out to investigate the nature of polymeric products in edible oils. Dimers from low-temp oxidation of methyl linoleate were compared with thermal dimers from high-temp polymerization of conjugated methyl linoleate. The distilled dimers were subjected to liquid-partition chromatographic separations on silicic acid columns as methyl esters, as free acids, and as methyl esters prepared by saponification and reesterification. Chromatographically isolated dimer fractions were also rechromatographed before and after each treatment. When thermal dimer esters are saponified and reesterified, chromatographic recoveries are quantitative, and the expected changes in polarity result; whereas, with oxidative dimer esters, gross changes in polarity occur. Chromatographic separations of dimer esters or their acids fractionate into distinct areas of increasing polarity. Presented at the AOCS Meeting, New Orleans, 1964. Honorable Mention, Bond Award Competition. A laboratory of the No. Utiliz. Res. & Dev. Div., ARS, USDA.     

Structure and Activity of NADPH‐Dependent Reductase Q1EQE0 from Streptomyces kanamyceticus,which Catalyses the R‐Selective Reduction of an Imine Substrate

NADPH‐dependent oxidoreductase Q1EQE0 from Streptomyces kanamyceticus catalyzes the asymmetric reduction of the prochiral monocyclic imine 2‐methyl‐1‐pyrroline to the chiral amine (R)‐2‐methylpyrrolidine with >99 % ee, and is thus of interest as a potential biocatalyst for the production of optically active amines. The structures of Q1EQE0 in native form, and in complex with the nicotinamide cofactor NADPH have been solved and refined to a resolution of 2.7 Å. Q1EQE0 functions as a dimer in which the monomer consists of an N‐terminal Rossman‐fold motif attached to a helical C‐terminal domain through a helix of 28 amino acids. The dimer is formed through reciprocal domain sharing in which the C‐terminal domains are swapped, with a substrate‐binding cleft formed between the N‐terminal subunit of monomer A and the C‐terminal subunit of monomer B. The structure is related to those of known β‐hydroxyacid dehydrogenases, except that the essential lysine, which serves as an acid/base in the (de)protonation of the nascent alcohol in those enzymes, is replaced by an aspartate residue, Asp187 in Q1EQE0. Mutation of Asp187 to either asparagine or alanine resulted in an inactive enzyme.     

Thermal modification of vegetable oils

This article reviews old and recent literature concerning the hypothesis that the Diels‐Alder reaction is the dominant reaction in the thermal polymerization of vegetable oil. Both triacylglycerol oils and methyl esters are used to show that this mechanism is unlikely to be a significant contributor en route to the reaction products. The products formed under a range of different reaction conditions are reviewed, including dimer acid, where Diels‐Alder chemistry is not claimed, to the polymerization of mono‐unsaturated methyl oleate in the presence of oxygen. In these, and even in the system where Diels‐Alder chemistry is claimed, the polymerization of conjugated methyl linoleate, six‐membered ring structures are not found in levels detectable by ¹³C NMR. Since such structures are formed by a Diels‐Alder reaction, it is unlikely that any more than 5% of the reaction could be formed by that method. Other factors against the Diels‐Alder contribution to this process, such as conformation and electron withdrawing ability of the substrates are also discussed.     

Bicyclic Peptide Inhibitor of Urokinase‐Type Plasminogen Activator: Mode of Action

The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptide‐based inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase‐type plasminogen activator (uPA), based on the established monocyclic peptide, upain‐2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across‐the‐ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain‐2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain‐2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also investigated the solution structures of the bicyclic peptide by NMR spectroscopy to map possible conformations. An X‐ray structure of the bicyclic‐peptide–uPA complex confirmed an interaction similar to that for the previous upain‐1/upain‐2–uPA complexes. These physical studies of the peptide–protease interactions will aid future designs of bicyclic peptide protease inhibitors.     

Effects of hydrogen on the properties of Si-incorporated diamond-like carbon films prepared by pulsed laser deposition

We have deposited unhydrogenated and hydrogenated Si-incorporated DLC (Si-DLC) films by pulsed laser deposition using KrF excimer laser, and systematically examined the structure and the mechanical and tribological properties of the films. Hydrogenated Si-DLC films were prepared by atomic-hydrogen irradiation during deposition. The Si/(Si+C) ratio in DLC films increased by atomic-hydrogen irradiation during deposition, indicating that the hydrogen etching is more effective for C atoms compared with Si atoms. The formation of Si–C bonds in the films and silicon oxides only at the surfaces was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. It was found that the atomic-hydrogen irradiation led to the formation of Si–H bonds to prevent the surface oxidation of the Si-DLC films. The scratch tests revealed that the critical loads of the films deposited with hydrogen were higher than those of the films deposited without hydrogen. We found that the moderately hydrogen-irradiated Si-DLC films tended to have higher wear resistance than the unhydrogenated Si-DLC films.     

Zur Chemie der cyclischen Fettsäuren

Cyclic Fatty Acids Following a review, the most important processes for preparing monomeric cyclic fatty acids are dealt with. In the alkali cyclization of triunsaturated fatty acids, formation of cyclizable isomers having a central cis-structure takes place preferentially compared to thermal ring closure. Compared to conjugated or isolated structure, cis/trans configuration of double bonds have stronger impact on distribution of isomers in cyclic acids formed. Isolated unsaturated trienoic fatty acids yield also bicyclic compounds having indanyl structure besides monocyclic compounds. Heterogeneous catalytic cyclization with Pd/C or Ni favours more extensive displacement of double bonds and disproportionation leading to formation of aromatics besides monoenoic and saturated fatty acids.     

Asymmetric Synthesis of Polyfunctionalized Mono‐, Bi‐, and Tricyclic Carbon Frameworks via Organocatalytic Domino Reactions

An asymmetric organocatalytic multi‐component domino reaction is used as a key process for the stereoselective synthesis of polysubstituted mono‐ and bicyclic cyclohexene‐carbaldehydes. Furthermore, the extension of the domino reaction and further synthetic transformations of the cascade products were investigated. The combination of the three‐step cascade with an intramolecular Diels–Alder reaction opens up an entry to tricyclic decahydroacenaphthylene and decahydrophenalene skeletons, which are valuable characteristic carbon cores of natural products.     

Synthesis and Inhibition Study of Bicyclic Iminosugar-Based Alkaloids,Scaffolds, and Libraries towards Glucosidase

A small library of bicyclic iminosugar-based alkaloids and scaffolds possessing a polyhydroxylated pyrrolidine and a varied ring skeleton have been synthesized. Through rapid diversification of the scaffold via an amide coupling with random carboxylic acids, structurally diverse bicyclic iminosugar-based libraries were prepared with substituent diversity, core diversity, and configurational diversity. This discovery process allowed us to efficiently sieve out potent and specific glycosidase inhibitors, and a bicyclic, conformationally restricted iminosugar was demonstrated to be more potent than the monocyclic ones in this study. The most potent and selective inhibitor discovered was found to have a K_i value of 71 nM against α-glucosidase.     

Low-temperature test reaction for hydride transfer on solid acid catalysts

A new model test reaction is proposed for the estimation of low-temperature hydride transfer (HT) activity of solid acids. The reaction of cyclohexene with isobutane on zeolite Beta, ZSM-5 and sulfated zirconia distinguished between disproportionation/hydrogen transfer and HT. The effects of acid site density, catalyst structure and interaction with isobutane are discussed.     

Alkylation of Benzene with Cyclic Ethers in Superacidic Media

Superacidic trifluoromethanesulfonic acid (triflic acid, TFSA) catalyzes the alkylation of benzene with various cyclic ethers. The characteristic products formed in the reaction of highly reactive oxiranes (methyloxirane, styrene oxide, and cyclohexene oxide) are phenyl-substituted compounds formed as a result of Friedel–Crafts-type mono- and dialkylation. Oxetanes (2-isopropyloxetane) and oxolanes (tetrahydrofuran, 2,5-dimethyltetrahydrofuran, 2,2,5,5-tetramethyltetrahydrofuran), in turn, undergo electrophilic cyclialkylative ring closure (cyclialkylation) to form mainly bicyclic compounds (tetralin, dihydronaphthalene, and naphthalene derivatives). In the majority of cases, alkylated products can be isolated in good to reasonable yields. Reactivity of cyclic ethers, product formation and product distributions are interpreted by taking into account ring strain, acidity of reaction mixtures and stability of carbocationic intermediates.