- [6, 7, 10, 11-13C4]-labelled leukotriene B4 synthesis: Standard for mass spectrometry determination and metabolic studies
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The mass spectrometry quantification and metabolic studies of leukotriene B4 (LTB4) in biological fluids require standards labelled with stable isotopes. This paper describes the synthesis of LTB4 labelled with 13C in positions 6, 7, 10 and 11 (1). These labelled carbons come from 13C2-acetylene. A labelled LTB4 is obtained with an isotopic enrichment of 99%. Copyright
- Treilhou, Michel,Couderc, Francois
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- A NEW APPROACH TO (+/-)-LEUKOTRIENE A4 METHYL ESTER
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A stereoselective synthesis of (2E,4Z,7Z)-2,4,7-tridecatrienol, a key intermediate in the synthesis of leukotriene A4 methyl ester, is established via alumina-promoted rearrangement of ethyl (7Z)-3,4,7-tridecatrienoate to ethyl (2E,4Z,7Z)-2,4,7-tridecatrienoate as a key step.
- Tsuboi, Sadao,Masuda, Toshihide,Takeda, Akira
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- A new efficient synthesis of (58,12S)-DiHETE
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An efficient synthesis of (5S,12S)-diHETE was realized by a Pd-Cu catalysed coupling of the chiral synthons 3 and 4 which were easily obtained by the kinetic resolution of the corresponding racemates using the Sharpless reagent.
- Chemin,Alami,Linstrumelle
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- Survey of volatile oxylipins and their biosynthetic precursors in bryophytes
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Oxylipins are metabolites which are derived from the oxidative fragmentation of polyunsaturated fatty acids. These metabolites play central roles in plant hormonal regulation and defense. Here we survey the production of volatile oxylipins in bryophytes and report the production of a high structural variety of C5, C6, C8 and C9 volatiles of mosses. In liverworts and hornworts oxylipin production was not as pronounced as in the 23 screened mosses. A biosynthetic investigation revealed that both, C18 and C20 fatty acids serve as precursors for the volatile oxylipins that are mainly produced after mechanical wounding of the green tissue of mosses.
- Croisier, Emmanuel,Rempt, Martin,Pohnert, Georg
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- A convergent strategy toward linear Cis-skipped polyenes
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An easy preparation of symmetric Cis-skipped polyenic hydrocarbons 1 to 5 combining the controlled classical Wittig reaction or the oxidative dimerization of phosphoranes is described.
- Sandri, Jacqueline,Soto, Thierry,Gras, Jean-Louis,Viala, Jacques
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- A short stereocontrolled synthesis of leukotriene B4
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A short convergent total synthesis of LTB4 1 is accomplished by an efficient palladium-catalyzed coupling reaction of two easily accessible chiral synthons 3 and 4.
- Chemin, Denis,Linstrumelle, Gerard
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- An Efficient Stereocontrolled Synthesis of 12(R)-HETE and 12(S)-HETE
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An efficient synthesis of 12(R) and 12(S) HETEs was realized by assembly of the easily obtainable synthons: optically pure iodo-alcohols 3(R) and 3(S) with the ester 4, followed by reduction with activated zinc.
- Chemin, Denis,Gueugnot, Sylvie,Linstrumelle, Gerard
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- Synthesis of 7-thiaarachidonic acid as a mechanistic probe of prostaglandin H synthase-2
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The mechanism by which prostaglandin synthase converts arachidonic acid to prostaglandin G2, creating five new chiral centers in the process, is still incompletely understood. The first radical intermediate has been characterized by EPR spectroscopy but subsequent proposed intermediates have not succumbed to detection. We report the synthesis of 7-thiaarachidonic acid designed to stabilize one of the proposed radical intermediates, which may allow its detection.
- McGinley, Chris M.,Jacquot, Cyril,van der Donk, Wilfred A.
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- Structure-Odor Relationships of (Z)-3-Alken-1-ols, (Z)-3-Alkenals, and (Z)-3-Alkenoic Acids
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(Z)-3-Unsaturated volatile acids, alcohols, and aldehydes are commonly found in foods and other natural sources, playing a vital role in the attractiveness of foods but also as compounds with chemocommunicative function in entomology. However, a systematic investigation of their smell properties, especially regarding humans, has not been carried out until today. To close this gap, the odor thresholds in air and odor qualities of homologous series of (Z)-3-alken-1-ols, (Z)-3-alkenals, and (Z)-3-alkenoic acids were determined by gas chromatography-olfactometry. It was found that the odor qualities in the series of the (Z)-3-alken-1-ols and (Z)-3-alkenals changed, with increasing chain length, from grassy, green to an overall fatty and citrus-like, soapy character. On the other hand, the odor qualities of the (Z)-3-alkenoic acids changed successively from cheesy, sweaty via plastic-like, to waxy in their homologous series. With regard to their odor potencies, the lowest thresholds in air were found for (Z)-3-hexenal, (Z)-3-octenoic acid, and (Z)-3-octenal.
- Lorber, Katja,Zeh, Gina,Regler, Johanna,Buettner, Andrea
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p. 2334 - 2343
(2018/03/21)
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- Catalytic asymmetric synthesis of Leukotriene B4
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Leukotriene B4 1 was prepared from two chiral synthons 8 and 14. The chiral secondary alcohols of 8 and 14 were constructed by BINOL/Ti(OiPr)4 catalyzed enantioselective alkynylzinc addition to aldehydes.
- Yang, Pengfei,Zhong, Jiangchun,Ji, Kaijie,Yin, Jingwei,Li, Shuoning,Wei, Siyuan,Zhou, Yun,Wang, Lifeng,Wang, Min,Bian, Qinghua
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p. 1596 - 1601
(2017/10/20)
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- 3-Aminoazetidin-2-one derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors suitable for systemic administration
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N-Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti-inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator-activated receptor α (PPAR-α). Thus, preventing PEA degradation by inhibiting NAAA may provide a novel approach for the treatment of pain and inflammatory states. Recently, 3-aminooxetan-2-one compounds were identified as a class of highly potent NAAA inhibitors. The utility of these compounds is limited, however, by their low chemical and plasma stabilities. In the present study, we synthesized and tested a series of N-(2-oxoazetidin-3-yl)amides as a novel class of NAAA inhibitors with good potency and improved physicochemical properties, suitable for systemic administration. Moreover, we elucidated the main structural features of 3-aminoazetidin-2-one derivatives that are critical for NAAA inhibition. Stability is the key: α-Amino-β-lactams were synthesized as amide derivatives, and the effect of the azetidin-2-one ring, the stereochemistry at the α-position, and the functionalization of the α-amino group were studied with regard to N-acylethanolamine acid amidase inhibitory potency and hydrolytic and plasma stability.
- Fiasella, Annalisa,Nuzzi, Andrea,Summa, Maria,Armirotti, Andrea,Tarozzo, Glauco,Tarzia, Giorgio,Mor, Marco,Bertozzi, Fabio,Bandiera, Tiziano,Piomelli, Daniele
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supporting information
p. 1602 - 1614
(2014/07/21)
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- Influence of the chemical structure on odor qualities and odor thresholds in homologous series of alka-1,5-dien-3-ones, alk-1-en-3-ones, alka-1,5-dien-3-ols, and alk-1-en-3-ols
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Odor qualities and odor thresholds in air in homologous series of synthesized alk-1-en-3-ols and alka-1,5-dien-3-ols and their corresponding ketones were evaluated by gas chromatography-olfactometry. In the series of the alk-1-en-3-ols and alk-1-en-3-ones the odor quality changed successively from pungent for the compounds with five carbon atoms via metallic, vegetable-like for the six- and seven-carbon odorants to mushroom-like for the compounds with eight and nine carbon atoms. With further increase in chain length the mushroom-like impression decreased and changed to citrus-like, soapy, or herb-like. In both series, two odor threshold minima were found for the six-carbon and also for the eight- and nine-carbon odorants, respectively. In contrast to this, the odor qualities in the series of the (Z)- and (E)-alka-1,5-dien-3-ols and their corresponding ketones did not change significantly with geranium-like, metallic odors and an increasing mushroom-like odor note with increasing chain length. The lowest thresholds were found for the eight- and nine-carbon (Z)-compounds, respectively.
- Lorber, Katja,Schieberle, Peter,Buettner, Andrea
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p. 1025 - 1031
(2014/03/21)
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- Influence of the chemical structure on odor qualities and odor thresholds in homologous series of alka-1,5-dien-3-ones, alk-1-en-3-ones, alka-1,5-dien-3-ols, and alk-1-en-3-ols
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Odor qualities and odor thresholds in air in homologous series of synthesized alk-1-en-3-ols and alka-1,5-dien-3-ols and their corresponding ketones were evaluated by gas chromatography-olfactometry. In the series of the alk-1-en-3-ols and alk-1-en-3-ones the odor quality changed successively from pungent for the compounds with five carbon atoms via metallic, vegetable-like for the six- and seven-carbon odorants to mushroom-like for the compounds with eight and nine carbon atoms. With further increase in chain length the mushroom-like impression decreased and changed to citrus-like, soapy, or herb-like. In both series, two odor threshold minima were found for the six-carbon and also for the eight- and nine-carbon odorants, respectively. In contrast to this, the odor qualities in the series of the (Z)- and (E)-alka-1,5-dien-3-ols and their corresponding ketones did not change significantly with geranium-like, metallic odors and an increasing mushroom-like odor note with increasing chain length. The lowest thresholds were found for the eight- and nine-carbon (Z)-compounds, respectively.
- Lorber, Katja,Schieberle, Peter,Buettner, Andrea
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p. 1025 - 1031
(2015/04/22)
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- Whole-cell one-pot biosynthesis of azelaic acid
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Polymers benefit from the use of biogenic resources such as fatty acids. They enable easy access to valuable monomeric building blocks, which, in comparison to their exclusively fossil counterparts, lead to products with improved physicochemical properties. Monomers of special interest are medium-chain dicarboxylic acids, which are not easy to obtain by traditional chemical means. Previously, we established an in vitro pathway that combined a 9-lipoxygenase and a 9/13-hydroperoxide lyase, which enabled the conversion of linoleic acid via a hydroperoxy intermediate into 9-oxononanoic acid, the precursor of azelaic acid. Herein, we aimed for the further development of the multi-enzyme cascade, which included the oxidation of 9-oxononanoic acid and the establishment of a suitable whole-cell catalyst. A detailed investigation of the simultaneous in vitro reaction setup revealed that both lipoxygenase activation and the subsequent hydroperoxide lyase reaction depend on the hydroperoxide reaction intermediate. For the activation of lipoxygenase, the hydroperoxide lyase activity, therefore, has to be significantly reduced. In accordance with these observations, we established a suitable dual-expression system and we further demonstrated that endogenous E. coli redox enzymes are feasible to oxidize 9-oxononanoic acid to azelaic acid. The resulting whole-cell catalyst is, therefore, able to perform the direct bioconversion of linoleic acid into azelaic acid. The use of organic solvent as the second phase improved the overall performance of the E. coli host strain. The developed one-pot, single-step process afforded 29 mg L-1 of azelaic acid within 8 h with a substrate conversion of 34 % and a selectivity of 47 %. Tiny polymer factories: An E. coli whole-cell catalyst is developed for the bioconversion of linoleic acid to azelaic acid, an important building block for biopolymers. The catalytic machinery of the prokaryotic host is equipped with two plant enzymes, a lipoxygenase, and a hydroperoxide lyase. Together with an endogenous oxidoreductase, this three-enzyme cascade reaction catalyzes the oxidative cleavage of the fatty acid substrate.
- Otte, Konrad B.,Kittelberger, Jens,Kirtz, Marko,Nestl, Bettina M.,Hauer, Bernhard
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p. 1003 - 1009
(2014/05/06)
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- Enantioselective synthesis of cyclopropyl δ-lactonealdehydes and dodecyl-5-ene-1-yne-3-ol: Advanced intermediates of solandelactone A and B
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A stereocontrolled synthesis of cyclopropyl δ-lactonealdehydes and dodecyl-5-ene-1-yne-3-ol is accomplished with predictable absolute stereochemistry via organocatalytic and catalytic asymmetric transfer hydrogenation reactions. The salient feature of this protocol is the genesis of chirality through an organocatalytic reaction and utilized for installing a critical bifunctional trans-cyclopropane motif, which is a key segment of every representative member of the oxylipin class of natural products such as solandelactone A and B.
- Kumaraswamy, Gullapalli,Ramakrishna, Gajula,Sridhar, Balasubramanian
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supporting information; experimental part
p. 1778 - 1782
(2011/05/05)
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- Chemo-enzymatic enantio-convergent asymmetric total synthesis of (S)-(+)-dictyoprolene using a kinetic resolution - Stereoinversion protocol
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A single enantiomer of a (stereo)chemically labile allylic-homoallylic alcohol was obtained in 91% e.e. and 96% yield from the racemate by employing a lipase-catalysed kinetic resolution coupled to in situ inversion under carefully controlled (Mitsunobu) conditions in order to suppress side reactions, such as elimination and racemisation. This technique was successfully applied to an enantio-convergent asymmetric total synthesis of the algal fragrance component (S)-dictyoprolene.
- Wallner, Andreas,Mang, Harald,Glueck, Silvia M.,Steinreiber, Andreas,Mayer, Sandra F.,Faber, Kurt
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p. 2427 - 2432
(2007/10/03)
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- Clean and Efficient Oxidation of Homoallylic and Homopropargylic Alcohols into β,γ-Unsaturated Aldehydes by The Dess-Martin Periodinane
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We describe the first efficient oxidation of homoallylic and homopropargylic alcohols to the corresponding very sensitive and unstable β,γ-unsaturated aldehydes by using Dess-Martin periodinane with a new neutral and anhydrous extraction protocol.
- Wavarin, Laurence,Viala, Jacques
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p. 326 - 330
(2007/10/03)
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- A convenient strategy for the synthesis of β,γ-unsaturated aldehydes and acids. A construction of skipped dienes
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A novel strategy is described for the synthesis of β,γ-unsaturated aldehydes which are the useful-synthons for the synthesis of arachidonic acid and other eicosanoid products. These β,γ-unsaturated aldehydes have been used in the total synthesis of arachidonic acid.
- Saha, Goutam,Basu, Manas K.,Kim, Seongjin,Jung, Young-Ju,Adiyaman, Yurdanur,Adiyaman, Mustafa,Powell, William S.,FitzGerald, Garret A.,Rokach, Joshua
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p. 7179 - 7183
(2007/10/03)
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- 12-Oxo-LTB4, a key pivotal intermediate in LTB4 metabolism
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The first total synthesis of the very unstable and elusive biochemical intermediate 5(S)-hydroxy-12-oxo-6(Z),8(E),10(E),14(Z)-eicosatetraenoic acid (12-oxo-LTB4) (2) has been accomplished. Incubation of the synthetic 12-oxo-LTB4 (2) with human keratinocytes produced 5(S),12-dihydroxy-6-glutathionyl-7(E),9(E),14(Z)-eicosatrienoic acid (c-LTB3) and 5(S),12-dihydroxy-6-cysteinylglycyl-7(E),9(E),14(Z)-eicosatrienoic acid (d-LTB3), two new intriguing mediators which have been identified recently during the incubations of LTB4 with keratinocytes. We have also confirmed the identity of 12-oxo-LTB4 prepared from porcine leukocytes by comparison with the synthetic material and identified the formation in these incubates of the 6-trans-isomer of 12-oxo-LTB4.
- Khanapure,Manna,Rokach,Murphy,Wheelan,Powell
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p. 1806 - 1813
(2007/10/02)
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- The first total synthesis of (-)-lipstatin
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A key step in the first total synthesis of the potent pancreatic lipase inhibitor (-)-lipstatin (1) is a diastereoselective Lewis acid-promoted [2 + 2] cycloaddition reaction between n-hexyl(trimethylsilyl)ketene (4) and (R)-(-)-(Z,Z)-3-[(tert-butyldimethylsilyl)oxy]-5,8-tetradecadienal (3), which is prepared from dimethyl (S)-(-)-malate.
- Pommier,Pons,Kocienski
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p. 7334 - 7339
(2007/10/03)
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- An Approach to the Syntheiss of (-)-Lipstatin by Wittig Reaction and Lewis Acid-promoted Cycloaddition
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The β-lactone moiety of (-)-lipstatin 1, a potent inhibitor of pancreatic lipase, is prepared via a Lewis acid-promoted cycloaddition between hexyltrimethylsilyl ketene 3 and the (Z,Z)-dienic aldehyde 4, obtained from hexenal by two stereoselective Wittig reactions.
- Pons, Jean-Marc,Pommier, Agnes,Lerpiniere, Joan,Kocienski, Philip
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p. 1549 - 1552
(2007/10/02)
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- Organoaluiminum-promoted claisen rearrangement of allyl vinyl ethers
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Unprecedentad stereochemical control has achieved in the Claisen of allyl vinyl of type 4 with certain bulky organoaluminum Thus, methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (reagent A) can be utilized for obtaining the (Z) isomer, (Z)-6, whereas the (E) isomer, (E)-6 was produced with methylaluminum bis(2,6-diphenylphenoxide) (reagent B). This organoaluminum-promoted Claisen rearrangement proceeds under very mild conditions with very good E and Z selectlvities. On the basis of the Claisen rearrangement of optically active substrate 7 with reagent A, the Z selectivity would be interpreted by the intervention of the chairlike transition-state conformation with the isobutyl substituent axial. The present organoalunminum-promoted Claisen rearrangement has successfully applied to the synthesis of (4E,7Z)-4,7-tridecadienyl acetate (15), a component of the sex of tuberworm moth, in stereoselective fashion. Furthermore, the Claisen rearrangement of bisallyl vinyi ether16 with reagent A or B has been found to involve the more substituted allylic system to furnish dienal 18 preferentially, not obtainable in the ordinary thermal rearrangement. This chemistry been further extended to the ionic rearrangement of dienyl vinyl ether 28 by using reagent A in a polar solvent the previously unknown, remote transfer of the vinyloxy moiety by [3,5]-sigmatropic rearrangement via ionic intermediate 29 has observed.
- Nonshita, Katsumasa,Banno, Hiroshi,Maruoka, Keiji,Yamamoto, Hishashi
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p. 316 - 322
(2007/10/02)
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- Highly Stereocontrolled Total Synthesis of Leukotriene B4, 20-Hydroxyleukotriene B4, Leukotriene B3, and Their Analogues
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A highly stereocontrolled and practical new method for synthesis of LTB4 (1), 20-OH-LTB4 (2), and LTB3 (3) has been developed, which uses the palladium catalyzed coupling reaction of the vinylborane 5, derived from the C(1)-C(9) fragment 4, with the corresponding C(10)-C(20) fragments 6a-c.The acetylene 4 was synthesized by palladium-copper-catalyzed coupling reaction of (trimethylsilyl)acetylene with the bromide 12, which was prepared from γ-(trimethylsilyl)allylic alcohol (S)-10 by bromination followed by debromosilylation.The alcohol (S)-10 was obtained by the kinetic resolution of the racemate dl-10 using the Sharpless reagent.The vinyl iodides 6a and 6b were prepared from racemic γ-(trimethylsilyl)allylic alcohols dl-17 and dl-28, respectively, by the Sharpless kinetic resolution followed by the reactions taking advantage of the reactivity of vinylsilane moiety, while the segment 6c was prepared by the Sharpless kinetic resolution of racemic γ-iodoallylic alcohol dl-34 followed by protection.By using this method, precursors of the radiolabeled LTB4, and 20-OH-LTB4, i.e., 14,15-didehydro-LTB4 (40) and 14,15-didehydro-20-OH-LTB4 (41), respectively, were also synthesized.Similarly the novel structural analogue of LTB 42-44 were prepared.
- Kobayashi, Yuichi,Shimazaki, Toshiyuki,Taguchi, Hideki,Sato, Fumie
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p. 5324 - 5335
(2007/10/02)
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- Synthesis of rigidified arachidonic acid analogues
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The synthesis of eight arachidonic acid analogues, rigidified by bridging the 7- and 10- or the 10-and 13-bis-allylic positions, is described.
- Stoller,Mioskowski,Millet,Sepulchre,Bellamy
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p. 5035 - 5038
(2007/10/02)
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- SIMPLE (R) CHIRALLY INDUCED SYNTHESES OF (+)-(2E,4E,8Z)-ETHYL 6-TETRAHYDROPYRANYLOXY-2,4,8-TETRADECATRIENOATE, A PROSYNTHON AT C-14 FOR LTB4.
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Two suitable enantioselective syntheses of the title compound (XI) or (XIa), through the "chirones" (V) or (Va) (identical, differing only in enantiomeric ratio) respectively obtained by chiralizing agents of Mukaiyama and Midland, are reported and compared.
- Leggeri, Paolo,Giacomo, Marcello Di,Azzolina, Ornella,Vercesi, Dina,Pirillo, Demetrio
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p. 2759 - 2776
(2007/10/02)
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- Synthesis of (+/-)-Dictyoprolene through (Z)-3-Nonenol, A Pheromonal Component of Anastrepha ludens
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Synthesis of (+/-)-dictyoprolene has been achieved through the transformation of (Z)-3-nonenol, a pheromonal component of female fruit flies (Anastrepha ludens) via three steps.
- Vig, O. P.,Kad, G. L.,Sabharwal, Arun,Sharma, Sanjiv,Dogra, Vijay
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- Three-Carbon Homologation Agent: New Preparation of (3,3-Diisopropoxypropyl)triphenylphosphonium Bromide
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A new and very efficient preparation of the title compound in one step using acrolein, triphenylphosphine and hydrobromic acid is described.This reagent used in the three-carbon homologation of carbonyl compounds gave β,γ-unsaturated aldehydes in good yields.
- Viala, Jacques,Santelli, Maurice
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p. 395 - 397
(2007/10/02)
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- Synthesis of (+/-)-Dictyoprolene
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2-Octyn-1-ol (II) on hydrogenation over Lindlars' catalyst gives (Z)-2-octen-1-ol (III) which on treatment with Corey's reagent provides (Z)-2-octenal (IV).Wittig reaction of methoxymethylenetriphenylphosphorane on IV yields the diene (V) which in turn furnishes 1,1-ethylenedioxynon-3(Z)-ene (VI) in good yield upon refluxing with ethylene glycol/PTS in benzene.Deketalization of VI with PTS in aq. acetone affords the aldehyde (VII).Grignard reaction on VII with vinylmagnesium bromide in anhyd. tetrahydrofuran gives undeca-1,5(Z)-dien-3-ol (VIII) which on acetylation using acetic anhydride/pyridine furnishes (+/-)-dictyoprolene (I).
- Vig, O.P.,Sharma, M.L.,Verma, N.K.,Malik, Neera
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p. 104 - 105
(2007/10/02)
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- THE SYNTHESIS OF NATURALLY OCCURRING 4-ALKYL- AND 4-ALKENYL-γ-LACTONES USING THE ASYMMETRIC REDUCING AGENT B-3-PINANYL-9-BORABICYCLONONANE
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4-Hydroxy-2-alkynoates of high enantiomeric purity, available from the reduction of the corresponding ketones with B-3-pinanyl-9-BBN, are converted to 4-substituted-γ-lactones found in beetle and deer pheromones.
- Midland, M. Mark,Tramontano, Alfonso
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p. 3549 - 3552
(2007/10/02)
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