Stereocontrolled total synthesis of leukotriene B4

Avignon-Tropis, M.; Berjeaud, J. M.; Pougny, Jean-René; Fréchard-Ortuno, I.; Guillerm, D.; Linstrumelle, G.

doi:10.1021/jo00028a046

Cited by 32 publications

(6 citation statements)

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“…Various organometallic cross-coupling reactions (Miyaura-Suzuki, [10][11][12] Sonogashira [13][14][15][16] ), stereoselective olefination reactions (Horner-Wadsworth-Emmons [17][18][19][20] or Wittig reactions [21][22][23] ), intramolecular [24] or radical [25] rearrangements, addition of Z-vinylbromide to aldehyde, and also addition of vinyl lithium reagents to pyrilium tetrafluoroborates [26] have been successfully reported to build the conjugated triene. These interesting papers document the difficulty in the syntheses of PUFA metabolites containing a conjugated triene and thus, some previously retrosynthetic approaches may be borrowed to achieve the synthesis of dihydroxylated docosatrienes.…”

Section: Introductionmentioning

confidence: 99%

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

Dayaker¹,

Balas²

2014

Chemistry A European J

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A versatile strategy featuring a Colvin rearrangement, hydrozirconation, a Sonogashira cross-coupling reaction and a Z-selective Wittig olefination, was successfully developed for the construction of a conjugated E,E,Z-triene subunit, flanked on both sides by two Z-allylic hydroxyl groups. This chemical pattern is found in many endogenous lipid metabolites such as maresin 1 (MaR1), neuroprotectin D1 (NPD1), and its aspirin triggered-isomer AT-NPD1, which not only counter-regulate inflammation but also actively orchestrate (at nanomolar doses) the resolution and termination program of acute inflammation while promoting wound healing, return to homeostasis and neuroprotection. Unlike previous approaches, the advantages of the present strategy are obvious, as it allows us to modify the nonpolar tail, the carboxylated head or both ends of the molecule without repeating the whole synthetic sequence (about 26-34 steps according to the literature). Thus, the first total syntheses of NPD1 methyl ester epimer (which can also be considered as an enantiomer of AT-NPD1) and its n-3 docosapentaenoic acid derived analogue were achieved from a highly functionalized and late advanced pivotal intermediate. This innovative route may be easily adapted to gain access to other dihydroxylated metabolites and analogues of polyunsaturated fatty acids containing a conjugated E,E,Z-triene subunit. Different epimers/diastereoisomers may be obtained by purchasing the suitable optically pure (S)- and/or (R)-1,2,4-butanetriol(s) as a chiral pool for both stereogenic centers.

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Section: Introductionmentioning

confidence: 99%

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

Dayaker¹,

Balas²

2014

Chemistry A European J

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“…This high-level expression system could be utilized to efficiently synthesize the enzymic isomer of LTB, whose chemical synthesis requires many reaction steps. (Avignon-Tropis et al, 1992;Guindon et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Coupling of recombinant 5‐lipoxygenase and leukotriene A₄ hydrolase activities and transcellular metabolism of leukotriene A₄ in Sf9 insect cells

Mancini

Evans

1993

European Journal of Biochemistry

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High‐level expression of human leukotriene (LT) A4 hydrolase has been established in Sf9 insect cells using the recombinant baculovirus system. LTA4 hydrolase activity in this system is at least 50‐fold higher than previously achieved in a bacterial cell system. Recombinant viral human LTA4 hydrolase (rvHLTA4h) was used for coinfection studies with recombinant viral 5‐lipoxygenase (rvH5LO). When Sf9 cells expressing 5‐lipoxygenase are incubated in the presence of A23187 and arachidonic acid, (5S)‐hydroperoxy‐6‐trans‐8,11,14‐cis‐eicosatetraenoic acid 5‐H(P)ETE and LTA4 are synthesized in a ratio of 5:1 for 5‐H(P)ETE/LT. Coexpression of 5‐lipoxygenase and LTA4 hydrolase in these insect cells results in the synthesis of 5‐H(P)ETE, LTA4 and in addition LTB4, and the ratio shifts to 2:1 for 5‐H(P)ETE/LT. The production of enzymically formed LTB4 after addition of arachidonic acid to the Sf9 cells coinfected with LTA4 hydrolase and 5‐lipoxygenase is the first demonstration of channeling of arachidonic acid to LTB4 in an engineered intact cell system. This delineates a novel biological system to synthesize significant amounts of the potent chemotactic agent, LTB4. Studies in which Sf9 cells infected with rvH5LO were incubated with Sf9 cells infected with rvHLTA4h resulted in export of LTA4 from the rvH5LO cells and transcellular metabolism of LTA4 to LTB4 in the rvHLTA4h Sf9 cells.

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“…Enantiomeric excess (GC): 98%. R f (PE/ethyl acetate 1 : 1): 0.57; [a] 25 D -14.4 (c 1.0, CDCl 3 ); (lit: 39 [a] 20 D -18.6, c 1.01 in CCl 4 ); n max (film)/cm -1 3436, 3286, 2954, 2924, 1731, 1437, 1159 1 H NMR, COSY (400 MHz, CDCl 3 ) d 4.39 (dt, 3 J 6.2 Hz, 4 J 2.1 Hz, 1H, H-5), 3.67 (s, 3H, OMe), 2.46 (d, 4 J 2.1 Hz, 1H, H-7), 2.37 (t, 3 J 7.1 Hz, 2H, H-2), 1.88-1.67 (m, 4H, H-3/H-4) ppm; 13 C NMR, HSQC, HMBC (101 MHz, CDCl 3 ) d 174.00 (C-1), 84.64 (C-6), 73.32 (C-7), 61.97 (C-5), 51.74 (OMe), 36.96 (C-4), 33.47 (C-2), 20.54 (C-3) ppm; GC-MS: m/z (%): 102 (13), 101 (24), 97 (5), 96 (9), 95 (8), 83 (6), 79 (54), 78 (7), 77 (16), 74 (39), 70 (31), 68 (9), 67 (6), 65 (7), 59 (28), 55 (38), 53 (23), 52 (59), 51 (25), 50 (21), 45 (5), 44 (7), 43 (34), 42 (100), 41 (40), 40 (13).…”

Section: (R)-5-hydroxy-7-trimethylsilylhept-6-ynoic Acid Methyl Estermentioning

confidence: 99%

“…R f (PE/ethyl acetate 2 : 1): 0.54; [a] 25 D +3.2 (c 0.1, CDCl 3 ); n max (film)/cm -1 3435, 2952, 2872, 1734, 1437; 1 H NMR, COSY (400 MHz, CDCl 3 ) d 5.86 (ddd, 3 J trans 16.9 Hz, 3 J cis 10.5 Hz, 3 J 6.2 Hz, 1H, H-6), 5.24 (pseudo-d, J app ~17.2 Hz, 1H, H-7 trans ), 5.12 (pseudo-d, J app ~10.4 Hz, 1H, H-7 cis ), 4.11 (m c , 1H, H-5), 3.67 (s, 3H, OMe), 2.35 (t, 3 (8), 126 (11), 102 (27), 101 (8), 99 (6), 98 (29), 85 (5), 83 (10), 81 (14), 74 (100), 71 (6), 70 (9), 59 (19), 57 (39), 55 (28), 44 (7), 43 (37), 42 (20), 41 (21), 40 (31), 39 (15); ESI-HRMS m/z calcd. for [2C 8 H 14 O 3 -CH 3 OH+Na] + : 307.1521, found: 307.1516.…”

Section: (R)-5-hydroxy-7-trimethylsilylhept-6-ynoic Acid Methyl Estermentioning

confidence: 99%

Structure elucidation of hypocreolide A by enantioselective total synthesis

et al. 2010

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The nonenolide hypocreolide A was isolated from culture filtrates of the ascomycete Hypocrea lactea. It exhibits moderate antimicrobial activity against various tested fungi and bacteria. Since neither the relative nor the absolute stereochemistry of the compound could be initially assigned, a stereochemically flexible total synthesis was developed. The two stereogenic centers were formed in high enantioselectivity and yield using transition metal catalyzed asymmetric reactions. While attempts to construct the ten-membered lactone in a ring-closing olefin metathesis gave disappointing results, a combination of cross metathesis and macrolactonization provided the title compound in nine steps and 12% overall yield.

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Stereocontrolled total synthesis of leukotriene B4

Cited by 32 publications

References 1 publication

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

Coupling of recombinant 5‐lipoxygenase and leukotriene A₄ hydrolase activities and transcellular metabolism of leukotriene A₄ in Sf9 insect cells

Structure elucidation of hypocreolide A by enantioselective total synthesis

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Stereocontrolled total synthesis of leukotriene B4

Cited by 32 publications

References 1 publication

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

A Versatile and Stereocontrolled Total Synthesis of Dihydroxylated Docosatrienes Containing a Conjugated E,E,Z‐Triene

Coupling of recombinant 5‐lipoxygenase and leukotriene A4 hydrolase activities and transcellular metabolism of leukotriene A4 in Sf9 insect cells

Structure elucidation of hypocreolide A by enantioselective total synthesis

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Coupling of recombinant 5‐lipoxygenase and leukotriene A₄ hydrolase activities and transcellular metabolism of leukotriene A₄ in Sf9 insect cells