- Total synthesis of leukotriene E4, a member of the SRS-A family
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Leukotriene E4 and two analogues homo-LTE4 and nor-LTE4 have been prepared via the intermediate epoxides. The epoxides were formed by the coupling of a polyenyne sulfonium salt with the required aldehyde-ester in a biphasic reaction system employing aqueous sodium hydroxide as the base for the generation of the ylide. Reduction of the acetylene bonds yielded the desired polyene epoxides which on treatment with L-cysteine methyl ester gave a 1:1 mixture of diastereomers from which the 5S,6R isomers were separated.
- Rosenberger,Newkom,Aig
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Read Online
- Aliphatic sulfates released from Daphnia induce morphological defense of phytoplankton: Isolation and synthesis of kairomones
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Six aliphatic sulfates, kairomones released from a crustacean Daphnia pulex induce morphological changes of phytoplankton Scenedesmus gutwinskii at ppb (10-9 g/mL) concentrations.
- Yasumoto, Ko,Nishigami, Akinori,Yasumoto, Mina,Kasai, Fumie,Okada, Yasuhiro,Kusumi, Takenori,Ooi, Takashi
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Read Online
- Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of 1,6-Enynes with Racemic Secondary Allylic Alcohols through Kinetic Resolution
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It has been established that a cationic rhodium(I)/P-phos complex catalyzes the asymmetric [2+2+2] cycloaddition of 1,6-enynes with racemic secondary allylic alcohols to produce the corresponding chiral bicyclic cyclohexenes, possessing three stereogenic
- Suzuki, Shunsuke,Shibata, Yu,Tanaka, Ken
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supporting information
p. 3698 - 3702
(2020/03/03)
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- Kinetics of the reaction of N,N-dimethylaniline with 1-bromoalk-2-ynes
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Quaternization of N,N-dimethylaniline with propargyl bromide, 1-bromobut-2-yne, and 1-bromooct-2-yne were studied. It was shown that, with the lengthening chain of the substituent at the triple bond, the quaternization rate tends to increase.
- Andreev,Ryzhakov,Sobolev
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p. 1486 - 1489
(2017/09/01)
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- Nanoporous gold catalyst for highly selective semihydrogenation of alkynes: Remarkable effect of amine additives
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We report for the first time the highly selective semihydrogenation of alkynes using the unsupported nanoporous gold (AuNPore) as a catalyst and organosilanes with water as a hydrogen source. Under the optimized reaction conditions, the present semihydrogenation of various terminal- and internal-alkynes affords the corresponding alkenes in high chemical yields and excellent Z-selectivity without any over-reduced alkanes. The use of DMF as solvent, which generates amines in situ, or pyridine as an additive is crucial to suppress the association of hydrogen atoms on AuNPore to form H2 gas, which is unable to reduce alkynes on the unsupported gold catalysts. The AuNPore catalyst can be readily recovered and reused without any loss of catalytic activity. In addition, the SEM and TEM characterization of nanoporosity show that the AuNPore catalyst has a bicontinuous 3D structure and a high density of atomic steps and kinks on ligament surfaces, which should be one of the important origins of catalytic activity.
- Yan, Mei,Jin, Tienan,Ishikawa, Yoshifumi,Fujita, Takeshi,Chen, Lu-Yang,Asao, Naoki,Chen, Ming-Wei,Yamamoto, Yoshinori,Minato, Taketoshi,Bao, Ming
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supporting information
p. 17536 - 17542,7
(2020/09/16)
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- Investigating inner-sphere reorganization via secondary kinetic isotope effects in the C-H cleavage reaction catalyzed by soybean lipoxygenase: Tunneling in the substrate backbone as well as the transferred hydrogen
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This work describes the application of NMR to the measurement of secondary deuterium (2° 2H) and carbon-13 (13C) kinetic isotope effects (KIEs) at positions 9-13 within the substrate linoleic acid (LA) of soybean lipoxygenase-1. The KIEs have been measured using LA labeled with either protium (11,11- h2-LA) or deuterium (11,11-d2-LA) at the reactive C11 position, which has been previously shown to yield a primary deuterium isotope effect of ca. 80. The conditions of measurement yield the intrinsic 2° 2H and 13C KIEs on kcat/Km directly for 11,11-d2-LA, whereas the values for the 2° 2H KIEs for 11,11-h2-LA are obtained after correction for a kinetic commitment. The pattern of the resulting 2° 2H and 13C isotope effects reveals values that lie far above those predicted from changes in local force constants. Additionally, many of the experimental values cannot be modeled by electronic effects, torsional strain, or the simple inclusion of a tunneling correction to the rate. Although previous studies have shown the importance of extensive tunneling for cleavage of the primary hydrogen at C11 of LA, the present findings can only be interpreted by extending the conclusion of nonclassical behavior to the secondary hydrogens and carbons that flank the position undergoing C-H bond cleavage. A quantum mechanical method introduced by Buhks et al. [J. Phys. Chem. 1981, 85, 3763] to model the inner-sphere reorganization that accompanies electron transfer has been shown to be able to reproduce the scale of the 2° 2H KIEs.
- Meyer, Matthew P.,Klinman, Judith P.
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supporting information; experimental part
p. 430 - 439
(2011/04/16)
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- Synthesis of carbazoles by gold(I)-catalyzed carbocyclization of 2-(enynyl)indoles
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A new synthetic protocol for carbazoles through gold(I)-catalyzed intramolecular hydroarylation of (Z)-2-(enynyl)indoles was achieved in good yields. The requisite (Z)-2-(enynyl)indoles were synthesized stereoselectively by trimethylgallium-promoted, Z-selective Wittig olefination of N-alkylindole-2-carboxaldehydes with propargyl ylides. Substrates possessing both alkyl as well as aromatic groups are well tolerated under these reaction conditions. Georg Thieme Verlag Stuttgart.
- Praveen, Chandrasekaran,Perumal, Paramasivan Thirumalai
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scheme or table
p. 521 - 524
(2011/04/17)
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- Structurally and stereochemically diverse tetrahydropyran synthesis through oxidative C-H bond activation
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Simple as pyran: Vinylsilane-substituted tetrahydropyrans, readily accessed through the oxidative C-H bond functionalization of silylallylic or propargylic ethers (see scheme; DDQ = 2,3-dichloro5,6-dicyano-l,4-benzoquinone), are versatile substrates for a wide range of functional group interconversions and stereocontrolled additions. These processes have applications in convergent target- or diversity-oriented synthesis strategies. (Chemical equation presented)
- Liu, Lei,Floreancig, Paul E.
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supporting information; scheme or table
p. 3069 - 3072
(2010/07/05)
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- Synthesis of linoleic acids combinatorially labeled at the vinylic positions as substrates for lipoxygenases
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Mammalian lipoxygenases have been implicated in a number of inflammation-related human diseases. Soybean lipoxygenase-1 is the archetypical example of known lipoxygenases. Here we report the synthesis of linoleic acid and (11,11)-d2-linoleic acid which are combinatorially labeled at the vinylic positions (9, 10, 12, and 13). Combinatorial labeling schemes allow for the simultaneous determination of KIEs in enzymatic reactions using NMR. Substrates are, thus, available as probes of detailed mechanism in kinetic isotope effect (KIE) studies of lipoxygenases.
- Meyer, Matthew P.,Klinman, Judith P.
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p. 3600 - 3603
(2008/09/19)
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- Synthesis and biological evaluation of several structural analogs of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand
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2-Arachidonoylglycerol (2-AG (1)) is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). There is growing evidence that 2-arachidonoylglycerol plays important physiological and pathophysiological roles in various mammalian tissues and cells,
- Suhara, Yoshitomo,Oka, Saori,Kittaka, Atsushi,Takayama, Hiroaki,Waku, Keizo,Sugiura, Takayuki
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p. 854 - 867
(2007/10/03)
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- Synthesis and trapping of some substituted 1-bromocyclopropenes
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Treatment of a number of 2-substituted 1,1,2-tribromocyclopropanes with MeLi at -78°C gave the corresponding 1-bromocyclopropenes, which were reacted with three cyclic dienes to yield the [4 + 2]-cycloadducts. Cycloaddition with 1,3-diphenylisobenzofuran
- Alnes, Karl F. S.,Sydnes, Leiv K.
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p. 483 - 500
(2007/10/03)
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- Palladium(II)-catalyzed enyne coupling reaction initiated by acetoxypalladation of alkynes and quenched by protonolysis of the carbon-palladium bond
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Divalent palladium-catalyzed inter- and intramolecular enyne coupling reactions initiated by acetoxypalladation of alkynes were developed. The reaction involves the acetoxypalladation of the alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond. The protonolysis of the carbon-palladium bond in the presence of bidentate nitrogen containing ligands is the key step in completing the Pd(II) catalytic cycle. The nitrogen-containing ligands, like halides, served to favor the protonolysis of the carbon-palladium bond over the β-H elimination in the Pd(II)-mediated reactions. The intermolecular coupling reactions provide an efficient method for synthesizing γ,δ-unsaturated carbonyls. The intramolecular coupling reactions offer a method to construct a variety of synthetically important carbo- and heterocycles. The asymmetric version of such a cyclization was developed with moderate enantioselectivity when employing pymox (pyridyl monooxazoline) as the ligand.
- Zhao, Ligang,Lu, Xiyan,Xu, Wei
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p. 4059 - 4063
(2007/10/03)
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- Concise synthesis of (8Z,11Z,14Z)-8,11,14-heptadecatrienal, (7Z,10Z,13Z)-7,10,13-hexadecatrienal, and (8Z,11Z)-8,11-heptadecadienal, components of the essential oil of marine green alga Ulva pertusa
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The long-chain aldehydes, (8Z,11Z,14Z)-8,11,14-heptadecatrienal, (7Z,10Z,13Z)-7,10,13-hexadecatrienal, and (8Z,11Z)-8,11-heptadecadienal, were concisely synthesized by using Grignard coupling, catalytic hydrogenation with the Lindlar catalyst, and oxidation with Dess-Martin periodinane as the key steps. Particularly, (8Z,11Z,14Z)-8,11,14-heptadecatrienal and (7Z,10Z, 13Z)-7,10,13-hexadecatrienal both possessed a seaweed-like odor.
- Akakabe, Yoshihiko,Washizu, Kensuke,Matsui, Kenji,Kajiwara, Tadahiko
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p. 1348 - 1352
(2008/02/01)
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- A direct route to conjugated enediynes from dipropargylic sulfones by a modified one-flask Ramberg-Baecklund reaction
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The reaction of dipropargylic sulfones with dibromodifluoromethane in the presence of alumina-supported KOH in dichloromethane solution results in facile rearrangement affording the corresponding conjugated linear and cyclic enediynes in good yields. This result shows that the direct transformation of a- and a′-hydrogen bearing sulfones assembles enediyne units without resorting to the prior preparation of the a-halo sulfone precursors in a separate step.
- Cao, Xiaoping,Yang, Yuying,Wang, Xiaolong
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p. 2485 - 2489
(2007/10/03)
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- Identification of potent odorants formed by autoxidation of arachidonic acid: Structure elucidation and synthesis of (E,Z,Z)-2,4,7-tridecatrienal
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The aroma composition of autoxidized arachidonic acid was characterized by aroma extract dilution analysis. The most potent odorant was trans-4,5-epoxy-(E)-2-decenal followed by 1-octen-3-one, (E,Z)-2,4-decadienal, (E,Z,Z)-2,4,7-tridecatrienal, (E,E)-2,4-decadienal, and hexanal. (E,Z,Z)-2,4,7-Tridecatrienal was unequivocally identified by mass spectrometry and nuclear magnetic resonance (NMR) data. The stereochemistry of its extended double-bond system was elucidated on the basis of NMR measurements. The target compound was synthesized in four steps starting with bromination of 2-octyn-1-ol, followed by copper-catalyzed coupling of the bromide with ethyl-magnesium bromide and (E)-2-penten-4-yn-1-ol. Partial hydrogenation of the resulting C13-compound with triple bonds in the positions C-4 and C-7 gave rise to (E,Z,Z)-2,4,7-tridecatrien-1,ol, which was finally oxidized to the target compound. It exhibits a typical egg-white-like, marine-like odor at low concentrations, and an intense orange-citrus, animal-like odor at higher concentrations. Its odor threshold was estimated by gas chromatography-olfactometry to be 0.07 ng/L air, Which is of the same order of magnitude as that reported for 1-octen-3-one and (E,E)-2,4-decadienal.
- Blank,Lin,Vera,Welti,Fay
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p. 2959 - 2965
(2007/10/03)
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- Synthesis and biological activities of novel structural analogues of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand
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Novel analogues of 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid receptor ligand, were developed. Chemical synthesis of these analogues (2-AGA105 and 2-AGA109) was accomplished starting from 2-octyn-1-ol and diethyl malonate and employing Wittig coupling of triene phosphonate with an aldehyde intermediate in a convergent and stereoselective manner. These analogues should be useful lead compounds for the development of novel 2-AG mimetics.
- Suhara, Yoshitomo,Nakane, Shinji,Arai, Shunsuke,Takayama, Hiroaki,Waku, Keizo,Ishima, Yoshio,Sugiura, Takayuki
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p. 1985 - 1988
(2007/10/03)
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- Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
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All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
- Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
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p. 4800 - 4818
(2007/10/03)
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- Synthesis of Analogues of Methyl Jasmonate using the Formation of Cyclopentenones from Alkyne (hexacarbonyl)dicobalt Complexes
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Numerous cyclopentenones including 5:5 and some 5:7 fused homo- and heterobicyclic derivatives have been synthesised for testing for jasmonate-like plant growth regulatory activity. The Khand reaction had been used as the key step and some known examples
- Clements, Carol J.,Dumoulin, Denis,Hamilton, David R.,Hudecek, Milan,Kerr, William J.,et al.
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p. 2658 - 2677
(2007/10/03)
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- Insect pheromones and their analogs LV. Synthesis of trideca-4E,7Z-dien-1-yl acetate - Component of the sex pheromone of Phthorimaea opercucella
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Starting from propargyl alcohol and using the thermal Claisen rearrangement at the stage of constructing the (E)-double bond, we have synthesized trideca-4E, 7Z-dien-1-yl acetate - a component of the sex pheromone of the potato moth Phthorimaea opercucella (Zeller).
- Odinokov,Vakhidov,Shakhmaev,Zorin
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p. 350 - 352
(2007/10/03)
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- Direct conversion of dipropargylic sulfones into (E)- and (Z)-Hex-3-ene-1,5-diynes by a modified one-flask Ramberg-Backlund reaction
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(E)- and (Z)-enediynes 7 are readily synthesized in good yields from a one-pot modified Ramberg-Backlund reaction from dipropargylic sulfones 5.
- Cao,Chan,Chow
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p. 1049 - 1052
(2007/10/03)
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- An efficient total synthesis of 5-(S)-HETE
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A short and convergent synthesis of (5S)-HETE 1a was accomplished by coupling of two easily accessible synthons 2 and 3a.
- Gueugnot, Sylvie,Alami, Mouad,Linstrumelle, Gerard,Mambu, Lengo,Petit, Yves,Larcheveque, Marc
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p. 6635 - 6646
(2007/10/03)
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- An Isotopic Study (2H and 18O) of the Enzymatic Conversion of Linoleic Acid into Colneleic Acid with Carbon Chain Fracture: the Origin of Shorter Chain Aldehydes
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Contrary to earlier reports, the divinyl 9-ether oxygen of colneleic acid is shown by experiment with 18O2 to originate from oxygen, not water.Using -9(S)-hydroperoxyoctadeca-10(E),12(Z)-dienoic acid, made enzymatically from synthetic linoleic acid, it is found that the distribution of deuterium as determined by NMR and mass spectrometry in the fractured carbon chain of colneic acid formed by potato enzyme, is consistent with the intervention of an epoxy carbonium ion intermediate.Though divinyl acids such as colneleic and colnelenic acid give the expected shorter chain aldehydes on treatment with aqueous acid, it is likely that the latter are formed in most plants by trapping of a monovinyl oxonium ion rather than by rehydration of colneleic and colnelenic acid.
- Crombie, Leslie,Morgan, David O.,Smith, Elisabeth H.
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p. 567 - 575
(2007/10/02)
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- DIRECT CONVERSION OF TETRAHYDROPYRANYLATED ALCOHOLS TO THE CORRESPONDING BROMIDES
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Various tetrahydro-2 pyranyl protected alcohols are converted into the corresponding bromides by PPh3/CBr4, with inversion of configuration, and high in yield.
- Wagner, A.,Heitz, M.-P.,Mioskowski, C.
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p. 557 - 558
(2007/10/02)
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- 2,5,6,7-tetranor-18,18,19,19-tetradehydro-4,8-inter-m-phenylene PGI2 derivatives
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Disclosed herein are novel prostaglandin I2 (PGI2) derivatives exhibiting excellent physiological activities, said derivatives being represented by the general formula: STR1 wherein R1, R2 and R3 are as defined herein.
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- 2,5,6,7-tetranor-4,8-inter-m-phenylene PGI2 derivatives
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Disclosed herein are novel prostaglandin I2 (PGI2) derivatives exhibiting excellent in vivo duration and activities, said derivatives being represented by the general formula: STR1 wherein R1, X, R2 and R3 are as defined herein.
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- PREPARATIVE SYNTHESIS OF TOSYLATES OF UNSATURATED ALCOHOLS AND UNSATURATED BROMIDES UNDER PHASE TRANSFER CONDITIONS
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A preparative synthetic method has been developed for tosylates of unsaturated alcohols and their conversion to bromides under phase transfer conditions in the case of alkyn-1-ols, E- and Z-alken-1-ols, 3-methyl-3-buten-1-ol and cyclopropylmethanol.
- Ishchenko, R. I..,Kovalev, B. G.,Khusid, A. Kh.
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p. 1076 - 1078
(2007/10/02)
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- Eicosatetraenehydroxamates: Inhibitors of 5-lipoxygenase
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The syntheses of 5-hydroxamyl and 5-hydroxamylmethyl-6,8,11,14,-eicosatetraenoic acids, which possess potent 5-lipoxygenase inhibitory activity, are described.
- Kerdesky,Holms,Schmidt et al.
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p. 2143 - 2146
(2007/10/02)
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- A CONVENITENT PREPARATION OF ALKYL HALIDES AND CYANIDES FROM ALCOHOLS BY MODIFICATION OF THE MITSUNOBU PROSCEDURE
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Alakanols are converted to the corresponding halides and cyanides with inversion of configuration by lithium salts in combination with a preformed complex of diethyl azodicarboxylate and triphenylphosphine.
- Manna, Sukumar,Falck, J. R.,Mioskowski, Charles
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p. 663 - 668
(2007/10/02)
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- Synthesis of ω-Tritiated and ω-Fluorinated Analogues of the Trail Pheromone of Subterranean Termites
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A series of unsaturated ω-fluoro alcohols have been prepared stereoselectively.These simple compounds are structural analogues of the trail pheromone of termites in the genus Reticulitermes.The toxicity of these ω-fluoro alcohols to R. flavipes is maximal for the C12 alcohols, and the attractiveness of these C12 analogues increases in the order saturated alkanol -12-fluoro alcohols and a -nonfluorinated analogue were prepared to examine the catabolism of the pheromone analogues.
- Carvalho, Joan F.,Prestwich, Glenn D.
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p. 1251 - 1258
(2007/10/02)
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- NEW STEREOCONTROLLED APPROACH TO SOME INSECT PHEROMONES VIA SILICON-DIRECTED BECKMANN FRAGMENTATION
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The major components of sex pheromones of potato tuberworm moth and Douglas fir tussock moth have been synthesized via the regio- and stereo-controlled Beckmann fragmentation assisted by trimethylsilyl group.
- Nishiyama, Hisao,Sakuta, Koji,Itoh, Kenji
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p. 223 - 226
(2007/10/02)
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- Synthesis of SRS-active compounds
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A chemical synthesis of an SRS-A active compound from the reaction product of 1-halo-2-octyne and the ether of 2-penten-4-yn-1-ol including intermediates in the synthesis, some of which being antagonists of SRS-A useful for treating allergic reactions.
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- Process for the preparation of esters of leukotriene A
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Esters of leukotriene A are conveniently prepared by reacting 9-oxo-5,6-trans-epoxynon-7(E)-enoates with 11-triphenylphosphoranylidene undec-6(Z),9(Z)-diene. Esters of leukotriene-A are useful intermediates in the synthesis of naturally occurring leukotrienes, which have been shown to be potent broncho-constricting substances. Novel intermediates to the esters of leukotriene A, 9-oxo-5,6-transepoxynon-7(E)-enoates and 7-oxo-5,6-transepoxyheptanoates, are disclosed.
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- SYNTHESE D'ALCOHOLS α-ALLENIQUES PAR REACTION D'ORGANOCHROMIQUES PROPARGYLIQUES SUR LES ALDEHYDES ET LES CETONES
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Propargylic bromides can be condensed with aldehydes and ketones in the presence of Hiyama's reagent (2CrCl3+LiAlH4 in THF) leading to α-allenic alcohols, to homopropargylic alcohols or to the mixture of both of them.The selectivity (or specificity) of this reaction depends on the substitution of the propargylic bromide, on the structure of the ketone, and on the presence of HMPT in the reaction mixture.In many cases, α- allenic alcohol has been specifically or very selectively obtained.The mechanism of the reaction and the influence of the various parameters are discussed.
- Place, Pierre,Verniere, Catherine,Gore, Jacques
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p. 1359 - 1368
(2007/10/02)
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- CONVERGENT SYNTHESIS OF LEUKOTRIENE A METHYL ESTER
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A convergent total synthesis of methyl 5,6-oxido-6,9,11,14-eicosapentaenoate from oct-2-yn-1-ol and methyl 4-formylbutyrate is described.
- Gleason, John G.,Bryan, D. Boles,Kinzig, Charles M.
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p. 1129 - 1132
(2007/10/02)
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