- 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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- An efficient total synthesis of leukotriene B4
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Lipid mediators have attracted great interest from scientists within the chemical, medicinal, and pharmaceutical research community. One such example is leukotriene B4 which has been the subject of many pharmacological studies. Herein, we report a convergent and stereoselective synthesis of this potent lipid mediator in 5% yield over 10 steps in the longest linear sequence from commercial starting materials. The key steps were a stereocontrolled acetate-aldol reaction with Nagao's chiral auxiliary and a Z-selective Boland reduction. All spectroscopic data were in agreement with those previously reported.
- Primdahl, Karoline Gangestad,Tungen, Jorn Eivind,Aursnes, Marius,Hansen, Trond Vidar,Vik, Anders
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p. 5412 - 5417
(2015/05/20)
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- COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes
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Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5 S -HETE as a substrate for COX-2 forming 5 S,15 S -diHETE, 5 S,15 R -diHETE, and 5 S,11 R -di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 ± 0.2 ng/106 cells (mean ± SEM, n = 6), reaching about half the level of LTB 4 (1.3 ± 0.5 ng/106 cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/106 cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 ± 0.05 ng/106 cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5 S,12 S -diHETE with the unusual 6 E,8 Z,10 E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A 4 -epoxide. Exogenous octadeuterated 5 S -HETE and 15 S -HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes. Copyright
- Tejera, Noemi,Boeglin, William E.,Suzuki, Takashi,Schneider, Claus
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scheme or table
p. 87 - 94
(2012/03/26)
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- Preparation of high specific activity tritium-labelled leukotriene B 4 suitable for radioligand binding assay
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We describe a method of preparation of high specific activity tritium-labelled leukotriene (LT) B4 from [5,6,8,9,11,12, 14,15- 3H] arachidonic acid (AA; 6.66 TBq/mmol) utilizing a LTB 4-synthesizing enzyme system from rat basophilic leukemia (RBL-1) cells. It was shown that both cyclooxygenase inhibitor indomethacin and adenosine 5′-triphosphate induced [3H] AA transformation to [3H] LTB4. In optimized conditions up to 15% of total radioactivity of the incubation mixture was present in [3H] LTB 4. A separation of [3H] LTB4 from other labelled C20:4 products was achieved by a three-step reverse phase-high-performance liquid chromatography in methanol- and acetonitrile-based solvent systems. [3H] LTB4 was confirmed to be identical to the naturally occurring LTB4 by a radioligand binding assay using a culture of HF1 cells that express a BLT1 receptor. Copyright
- Schramm, Stanislav I.,Nagaev, Igor Yu.,Sabirsh, Alan,Shevchenko, Valeriy P.,Arkhipova, Anastasiya S.,Haeggstroem, Jesper Z.,Myasoedov, Nikolay F.
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p. 101 - 105
(2008/09/20)
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- An atom-economic and selective ruthenium-catalyzed redox isomerization of propargylic alcohols. An efficient strategy for the synthesis of leukotrienes
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Catalytic ruthenium complexes in conjunction with an indium cocatalyst and Broensted acid isomerize primary and secondary propargylic alcohols in good yields to provide trans enals and enones exclusively. Readily available indenylbis(triphenylphosphine)ruthenium chloride, in the presence of indium triflate and camphorsulfonic acid, gives the best turnover numbers and reactivity with the broadest range of substrates. Deuterium labeling experiments suggest that the process occurs through propargylic hydride migration followed by protic cleavage of the resultant vinylruthenium intermediate. Application of this method to the synthesis of leukotriene B4 demonstrates its utility and extraordinary selectivity.
- Trost, Barry M.,Livingston, Robert C.
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supporting information; experimental part
p. 11970 - 11978
(2009/02/05)
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- Total synthesis of 12(R)-HETE, 12(S)-HETE, 2H2-12(R)-HETE and LTB4 from racemic glycidol via hydrolytic kinetic resolution
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The total synthesis of 12(R)-HETE, 12(S)-HETE (Samuelsson's HETE), [14,15-2H2]-12(R)-HETE and Leukotriene B4 from racemic glycidol is described. The key steps are the hydrolytic kinetic resolution of racemic TES-glycidol with salen-Co catalyst and the selective oxidation of primary silyl ethers, in the presence of secondary ones, under Swern conditions to give a short entry to both enantiomers of 12-HETE and LTB4.
- Rodríguez,Nomen,Spur,Godfroid,Lee
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- Application of the low-valent titanium reductive elimination of 1,6-dibenzoate-2,4-dienes to the total synthesis of 6(E)-5(S)-12(R)-leukotriene B4
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A stereoselective synthesis of 6(E)-5(S)-12(R)-leukotriene B4 is described in this paper, using a novel reaction, the low-valent titanium induced reductive elimination of a 1,6-dibenzoate-2,4-diene, for the selective synthesis of the trans-trie
- Solladie, Guy,Stone, Guy B.,Hamdouchi, Chafiq
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p. 1807 - 1810
(2007/10/02)
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- Application of Sodium Amalgam Reductive Elimination of Allylic Dibenzoates to the Total Synthesis of 5(S)-12(R) Leukotriene B4
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A stereoselective synthesis of 5(S)-12(R) LTB4 is described in this paper using a novel reaction, the sodium amalgam induced reductive elimination of allylic dibenzoates for the selective synthesis of the E,E,Z-triene moiety.The creation of the
- Solladie, Guy,Urbano, Antonio,Stone, Guy B.
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p. 6489 - 6492
(2007/10/02)
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- Use of the Two Enantiometers of 7,7-Dimethylbicyclohept-2-en-6-one to form Complementary Optically Active Synthons in a Convergent Synthesis of Leukotriene-B4
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The acetate (+/-)-4 was resolved by an enantioselective hydrolysis catalysed by porcine pancreatic lipase.The resultant alcohol (-)-3 and the optically active ester (+)-4 were converted into the ketones (+)-2 and (-)-2 respectively.The ketone (+)-2 was el
- Cotterill, Ian C.,Jaouhari, Rabih,Dorman, Gyoergy,Roberts, Stanley M.,Scheinmann, Feodor,Wakefield, Basil J.
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p. 2505 - 2512
(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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- An efficient synthesis of leukotriene B4
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Leukotriene B4 (5S, 12R) and its epimer (5R, 12R) have been prepared by coupling a chiral hydroxy vinyl borane with a racemic vinyl iodide, followed by the easy separation of the thus formed diastereomers.
- Avignon-Tropis,Treilhou,Lebreton,Pougny,Frechard-Ortuno,Huynh,Linstrumelle
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p. 6335 - 6336
(2007/10/02)
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- Total Synthesis of Leukotriene B44> and Homo-LTB4 from D-Mannitol
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A convergent total synthesis of leukotriene B4 and its homo analogue has been carried out via enantiomerically pure α-hydroxy aldehydes, chiral key intermediates obtained from D-mannitol and connected at a four carbon atom interval by Wittig re
- Merrer, Yves Le,Gravier-Pelletier, Christine,Micas-Languin, Dominique,Mestre, Francoise,Dureault, Annie,Depezay, Jean-Claude
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p. 2409 - 2416
(2007/10/02)
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- A Chemoenzymatic Synthesis of Leukotriene B4
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A total synthesis of leukotriene B4 (1) is accomplished by the assembly of the key chirons 2 and 3, which are prepared via enzymatic methods.
- Han, Chao-Qi,DiTullio, Dennis,Wang, Yi-Fong,Sih, Charles J.
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p. 1253 - 1258
(2007/10/02)
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- SYNTHESIS OF 5S,12S-diHETE (LTBx)
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The total synthesis of 5S,12S-diHETE (LTBx) was completed.The Wittig reaction of phosphorane 8 and chiral aldehyde 9 provided the key step to form the C-20 chain.
- Adams, Julian,Leblanc, Yves,Rokach, Joshua
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p. 1227 - 1230
(2007/10/02)
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- A GENERAL AND STEREOCONTROLLED TOTAL SYNTHESIS OF LEUKOTRIENE B4 AND ANALOGUES
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A new, general, and stereocontrolled total synthesis of leukotriene B4 (1) is disclosed.The application of the methodology to the synthesis of several novel analogues of leukotriene B4 is also described.
- Nicolaou, K. C.,Zipkin, R. E.,Dolle, R. E.,Harris, B. D.
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p. 3548 - 3551
(2007/10/02)
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- SIMPLE EFFICIENT SYNTHESIS OF LTB4 AND 12-epi-LTB4
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Using L- and D-arabinose respectively as the source of chirality at C-12 in LTB4, efficient new syntheses of LTB4 and 12-epi-LTB4 have been realized.
- Zamboni, Robert,Rokach, Joshua
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p. 2631 - 2634
(2007/10/02)
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- STEREOSPECIFIC SYNTHESIS OF LEUKOTRIENE B4 (LTB4)
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A stereospecific and chirally economical synthesis of LTB4 starting from 2-deoxy-D-ribose is reported as part of a comprehensive and efficient approach to the Leukotrienes (A, B, C, D, E).The process includes a novel approach to chiral dienic synthons.
- Guindon, Yvan,Zamboni, Robert,Cheuk-Kun Lau,Rokach, Joshua
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p. 739 - 742
(2007/10/02)
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- STEREOSPECIFIC TOTAL SYNTHESIS OF 12-(R)- AND 12-(S) FORMS OF 6-TRANS LEUKOTRIENE B
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Non enzyamatic hydration of leukotriene A (1), the biogenetic precursor of leukotriene B (2) affords among other products two diastereomeric 6-trans-isomers of 2, the first stereospecific and efficient syntheses of which are recorded herein.
- Corey, E. J.,Marfat, Anthony,Hoover, Dennis J.
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p. 1587 - 1590
(2007/10/02)
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- A STEREOCONTROLLED AND EFFECTIVE SYNTHESIS OF LEUKOTRIENE B (1).
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An efficient synthesis of leukotriene B (1) is reported which renders this important substance accessible in quantity.The process is convergent and includes a novel method for stereospecific generation of the conjugated triene unit.
- Corey, E. J.,Marfat, Anthony,Munroe, John,Kim, Kwan Soo,Hopkins, Paul B.,Brion, Francis
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p. 1077 - 1080
(2007/10/02)
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