- Kinetics and mechanism of hydration of o-thioquinone methide in aqueous solution. Rate-determining protonation of sulfur
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(Chemical Equation Presented) o-Thioquinone methide, 2, was generated in aqueous solution by flash photolysis of benzothiete, 1, and rates of hydration of this quinone methide to o-mercaptobenzyl alcohol, 3, were measured in perchloric acid solutions, using H2O and D2O as the solvent, and also in acetic acid and tris(hydroxymethyl)methylammonium ion buffers, using H2O as the solvent. The rate profiles constructed from these data show hydronium-ion-catalyzed and uncatalyzed hydration reaction regions, just like the rate profiles based on literature data for hydration of the oxygen analogue, o-quinone methide, of the presently examined substrate. Solvent isotope effects on hydronium-ion catalysis of hydration for the two substrates, however, are quite different: kH/kD = 0.42 for the oxygen quinone methide, whereas kH/kD = 1.66 for the sulfur substrate. The inverse nature (kH/kD a preequilibrium proton-transfer reaction mechanism, with protonation of the substrate on its oxygen atom being fast and reversible and capture of the benzyl-type carbocationic intermediate so formed being rate-determining. The normal direction (kH/kD > 1) of the isotope effect in the sulfur system, on the other hand, suggests that protonation of the substrate on its sulfur atom is in this case rate-determining, with carbocation capture a fast following step. A semiquantitative argument supporting this hypothesis is presented.
- Chiang, Yvonne,Kresge, A. Jerry,Sadovski, Oleg,Zhan, Hao-Qiang
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Read Online
- Synthesis and antiproliferative activity of sulfa-Michael adducts and thiochromenes derived from carbohydrates
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The Michael addition reactions of carbohydrate-derived nitroalkenes with ethyl thioglycolate and 2-mercaptobenzyl alcohol were studied. Reactions were conducted under mild, solvent-free conditions with DABCO as a catalyst, affording the corresponding adducts in good yields. Furthermore, compounds resulting from the addition with 2-mercaptobenzyl alcohol were used as starting materials for the synthesis of chiral 3-nitro-2H-thiochromenes. For some of the compounds synthesized herein, the antioxidant and antiproliferative activities against a panel of human solid tumor cell lines were assayed and compared with those of carbohydrate-nitroalkene substrates.
- Luque-Agudo,Albarrán-Velo,Fernández-Bola?os,López,Light,Padrón,Lagunes,Román,Serrano,Gil
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Read Online
- A cascade deprotonation/intramolecular aldol reaction of α-carbonyl sulfonium ylides with 2-mercaptoindole-3-carbaldehydes and 2-mercaptobenzaldehydes to access thieno[2,3-b]indoles and benzothiophenes
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The first catalyst-free cascade deprotonation/intramolecular aldol reaction of α-carbonyl sulfonium ylides with 2-mercaptoindole-3-carbaldehydes and 2-mercaptobenzaldehydes was developed. A series of thieno[2,3-b]indoles and benzothiophenes were smoothly obtained in high to excellent yields. The salient features of the protocol include catalyst-free conditions, an environment-friendly solvent, broad substrate scope, and large-scale synthesis.
- Yang, Lei,Zhou, Shun,Zhao, Jian-Qiang,You, Yong,Wang, Zhen-Hua,Zhou, Ming-Qiang,Yuan, Wei-Cheng
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supporting information
p. 3678 - 3686
(2021/05/05)
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- DEPALMITOYLATING COMPOSITIONS AND THE USE THEREOF
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Disclosed herein, inter alia, are depalmitoylating compounds, compositions, and methods of use thereof.
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Paragraph 0359; 0369-0370
(2021/02/19)
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- Visible-light induced photo-click and release strategy between monoarylsydnone and phenoxylfumarate
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We report a visible-light induced photo-click and release platform between monoarylsydnone (MASyd) and phenoxylfumarates. The pyrazoline produced by the cycloaddition undergoes a photo-aromatization to form a fluorescent pyrazole. Meanwhile, the photo-aro
- Li, Baolin,Liu, Hui,Shen, Xin,Xie, Xinyu,Yu, Zhipeng,Zhao, Xiaohu,Zheng, Tingting,Zheng, Yuanqin
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supporting information
p. 8135 - 8138
(2021/08/23)
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- Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model
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In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 μM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 μM caused a significant (P 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and ?9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer.
- Jia, Yan,Si, Lihui,Lin, Ruixin,Jin, Hongjuan,Jian, Wenwen,Yu, Qing,Yang, Shuli
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- Silver-Mediated Oxidative Decarboxylative Trifluoromethylthiolation of Coumarin-3-carboxylic Acids
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The introduction of trifluoromethylthio groups into organic compounds, in particular heterocycles, is important because of the prevalence of these structures in medicinally and agriculturally relevant molecules. Herein, the silver-mediated oxidative decarboxylative trifluoromethylthiolation of coumarin-3-carboxylic acids is reported. This methodology utilizes existing carboxylic acid functionalities for the direct conversion to CF3S groups and results in a broad scope of 3-trifluoromethylthiolated coumarins, including analogues of natural products, in moderate to excellent yields.
- Li, Minghao,Petersen, Jeffrey L.,Hoover, Jessica M.
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supporting information
p. 638 - 641
(2017/02/10)
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- Sulfinato Iron(III) complex for electrocatalytic proton reduction
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We report the first example of a sulfinato Fe(III) complex acting as a highly active electrocatalyst for proton reduction. The sulfinate binds to the metal through oxygen, resulting in a seven-membered chelate ring that is likely hemilabile during catalys
- Cavell, Andrew C.,Hartley, Carolyn L.,Liu, Dan,Tribble, Connor S.,McNamara, William R.
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p. 3325 - 3330
(2015/04/14)
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- The structural and electrochemical consequences of hydrogenating copper N2S2 Schiff base macrocycles
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A series of cis and trans tetradentate copper macrocyclic complexes, of ring size 14-16, that employ amine and thioether donor groups are reported. Apart from 5,6,15,16-bisbenzo-8,13-diaza-1,4-dithia-cyclohexadecane copper(I) (cis-[Cu(H4Nb
- Trotter, Katherine D.,Taylor, Michelle K.,Forgie, John C.,Reglinski, John,Berlouis, Leonard E.A.,Kennedy, Alan R.,Spickett, Corinne M.,Sowden, Rebecca J.
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experimental part
p. 1529 - 1538
(2010/08/05)
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- Mechanistic insights into the rhodium-catalyzed intramolecular ketone hydroacylation
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[Rh((fl)-DTBM-SEGPHOS)]BF4 catalyzes the intramolecular hydroacylation of ketones to afford seven-membered lactones in large enantiomeric excess. Herein, we present a combined experimental and theoretical study to elucidate the mechanism and origin of selectivity in this C-H bond activation process. Evidence is presented for a mechanistic pathway involving three key steps: (1) rhodium(I) oxidative addition into the aldehyde C-H bond, (2) insertion of the ketone C=O double bond into the rhodium hydride, and (3) C-O bond-forming reductive elimination. Kinetic isotope effects and Hammett plot studies support that ketone insertion isthe turnover-limiting step. Detailed kinetic experiments were performed using both 1,3- bis(diphenylphosphino)propane (dppp) and (R)-DTBM-SEGPH OS as ligands. With dppp, the keto-aldehyde substrate assists in dissociating a dimeric precatalyst 8 and binds an active monomeric catalyst 9. With [Rh((R)-DTBM-SEGPHOS)]BF4, there is no induction period and both substrate and product inhibition are observed. In addition, competitive decarbonylation produces a catalytically inactive rhodium carbonyl species that accumulates over the course of the reaction. Both mechanisms were modeled with a kinetics simulation program, and the models were consistent with the experimental data. Density functional theory calculations were performed to understand more elusive details of this transformation. These simulations support that the ketone insertion step has the highest energy transition state and reveal an unexpected interactionbetween the carbonyl-oxygen lone pair and a Rh d-orbital in this transi tion state structure. Finally, a model based on the calculated transition-state geometry is proposed to rationalize the absolute sense of enantioinduction observed using (R)-DTBM-SEGPHOS as the chiral ligand.
- Shen, Zengming,Dornan, Peter K.,Khan, Hasan A.,Woo, Tom K.,Dong, Vy M.
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supporting information; experimental part
p. 1077 - 1091
(2009/06/28)
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- Construction of fused heterocyclic architectures by formal [4+l]/[3+2] cycloaddition cascade of sulfur ylides and nitroolefins
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[Chemical equation presented] Under control: A format [4+1]/[3+2] cycloaddition cascade of sulfur ylides and alkene-tethered nitroolefins has been developed, and provides an efficient synthesis of fused polycyclic heterocyclic compounds in good to excelle
- Lu, Liang-Qiu,Li, Fang,An, Jing,Zhang, Ji-Ji,An, Xiao-Lei,Hua, Qiu-Lin,Xiao, Wen-Jing
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supporting information; scheme or table
p. 9542 - 9545
(2010/03/25)
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- A novel hydride-mediated reductive rearrangement of amide: a facile synthesis of pyrimidyl and triazinyl amines
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LiAlH4 and NaBH4 were found to mediate the conversion of 2-(pyrimidyl-2-ylsulfanyl)-N-arylbenzamides and 2-(triazinyl-2-ylsulfanyl)-N-arylbenzamides into pyrimidyl and triazinyl amines under notably mild conditions via a novel reductive rearrangement mechanism. These reactions invent a new route to prepare amines, which are a kind of important biologically active compounds and provide the first insight into a novel hydride-promoted reductive rearrangement of amides.
- Chen, Xiang,Wu, Jun,Shang, Zhicai,Chen, Meifeng,Sun, Yanping,Lv, Jing,Lei, Meikang,Zhang, Peizhi
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p. 495 - 499
(2008/04/13)
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- Synthesis and biological evaluation of sulfur-containing cinnamate and salicylate derivatives
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UV irradiation induced formation of reactive oxygen radical species and matrix metalloproteinases (MMPs) are thought to be involved in photo-damage to the skin. MMP-1 is the major collagenolytic enzyme responsible for collagen destruction in skin tissue. To develop new anti-photoaging agents, a series of 2,2′-dithiocinnamate derivatives and 2,2′-dithio or 2-thiobenzoate derivatives were designed and synthesized. The biological activities of the synthesized compounds were assayed for ABTS [2,2′-azinobis-(3-ethyl-benzo- thiazoline-6-sulfonic acid)] radical scavenging activity, MMP-1 inhibitory activity, and cytotoxicity to human dermal fibroblast cells. Compounds with potential of resistance to UV irradiation were identified. These compounds are expected to be useful for preventing photo-damage to the skin.
- Chiang, Chih-Chia,Chang, Tsu-Chung,Tsai, Hou-Jen,Hsu, Ling-Yih
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p. 369 - 373
(2008/09/20)
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- Dialkyl 2H-1-benzothiopyran-2,3-dicarboxylates via intramolecular Wittig reaction
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Reaction of 3-mercaptobenzaldehyde (1) with dialkyl acetylenedicarboxylate in the presence of triphenylphosphine leads to the corresponding 2H-1-benzothiopyran 2,3-diesters.
- Hekmatshoar, Rahim,Javanshir, Shahrzad,Heravi, Majid M.
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- Enantioselective formation of quaternary stereocenters using the catalytic intramolecular Stetter reaction
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Asymmetric formation of quaternary stereocenters has been accomplished using the catalytic intramolecular Stetter reaction. A?variety of tethered aldehydes and Michael acceptors are cyclized in excellent yields and enantioselectivities.
- Moore, Jennifer L.,Kerr, Mark S.,Rovis, Tomislav
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p. 11477 - 11482
(2007/10/03)
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- Synthesis of substituted dihydrobenzothiopyrans and dihydrobenzopyrans by cation-mediated cyclisation reactions
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Treatment with acid of thiosalicylaldehyde- and salicylaldehyde-derived phenyl 3-phenyl-2-propenyl thioethers and ethers possessing latent oxonium ion functionality triggers simple or tandem cyclisation to give substituted dihydrobenzothiopyrans and dihyd
- Bonfanti, Jean-Fran?ois,Craig, Donald
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p. 3719 - 3723
(2007/10/03)
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- Titanium reagents for the synthesis of 2-substituted benzo[b]thiophenes on the solid phase
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Titanium(IV) benzylidenes (Schrock carbenes) bearing a masked sulfur nucleophile in the ortho position were generated from thioacetals with use of low-valent titanocene complex Cp2Ti[P(OEt)3]2 and alkylidenated Merrifield resin-bound esters to give enol ethers. Treatment of the resin-bound enol ethers with a 5:5:90 mixture of TFA, TFAA, and dichloromethane led to cleavage from resin, removal of the tert- butyldimethylsilyl (TBDMS) protecting group, and concomitant cyclization to complete the traceless solid-phase synthesis (SPS) of benzothiophenes. Switching the nature of the linker from acid-stable to acid-sensitive ensured good purity.
- Roberts, Christine F.,Hartley, Richard C.
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p. 6145 - 6148
(2007/10/03)
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- Synthesis and biological activity of sulfur-containing aryl-aldehyde Schiff bases.
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A series of chemically modified aryl-aldehyde Schiff bases has been synthesized and tested for their antioxidant activity and radiation protection. We observed that disulfide-containing aryl-aldehyde Schiff base 6c exhibited potent free radical scavenging
- Jiang, Jyh-Jia,Chang, Tsu-Chung,Hsu, Wen-Lin,Hwang, Jing-Min,Hsu, Ling-Yih
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p. 1307 - 1310
(2007/10/03)
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- Chelation-assisted intramolecular hydroacylation: Synthesis of medium ring sulfur heterocycles
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Medium ring sulfur heterocycles are prepared from ω-alkenals and alkynals containing a sulfur tether atom via a novel chelation-assisted intramolecular hydroacylation catalyzed by rhodium(I).
- Bendorf, Holly D.,Colella, Christine M.,Dixon, Elizabeth C.,Marchetti, Melissa,Matukonis, Alicia N.,Musselman, Jeffrey D.,Tiley, Tara A.
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p. 7031 - 7034
(2007/10/03)
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- Optimization of a somatostatin mimetic via constrained amino acid and backbone incorporation
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Constrained analogues 5-7 of the potent and subtype selective somatostatin mimetic 1 were prepared by incorporating conformational constraints into the nine-membered heterocyclic scaffold. Each constrained peptidomimetic showed an altered activity profile relative to lead compound 1, with compound 7 exhibiting a 25-fold and 2-fold binding enhancement against somatostatin receptor subtypes sst4 and sst5, respectively. (C) 2000 Elsevier Science Ltd.
- Souers, Andrew J.,Rosenquist, Asa,Jarvie, Emma M.,Ladlow, Mark,Feniuk, Wasyl,Ellman, Jonathan A.
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p. 2731 - 2733
(2007/10/03)
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- Novel radiotracers for imaging the serotonin transporter by positron emission tomography: Synthesis, radiosynthesis, and in vitro and ex vivo evaluation of 11C-labeled 2-(phenylthio)araalkylamines
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A series of four 2-(phenylthio)araalkylamines have been radiolabeled with 11C and evaluated as potential radiotracers for imaging the serotonin transporter (SERT) by positron emission tomography (PET). All four candidates display high affinity
- Wilson,Ginovart,Schmidt,Meyer,Threlkeld,Houle
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p. 3103 - 3110
(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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- Benzodiazepine analogues. Part 15. Synthesis of benzoxathiepine derivatives
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Stepwise cyclisation sequences have provided access to a series of novel 4-phenyl-3,4-dihydro-1,5-benzoxathiepine-2-ones and 2- and 3-phenyl-4,1-benzoxathiepine analogues.
- Gelebe, Aifheli C.,Kaye, Perry T.
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p. 4459 - 4475
(2007/10/03)
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- Rotenoid Synthesis by Wadsworth-Emmons Coupling and Mukaiyama Cyclisation: Application to 5-Thiorotenoids
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A new synthesis of general applicability to rotenoid structures is described, through its specific objectives were 5-thiorotenoids.The synthons carrying the A/B- and the B/C-ring components are coupled by Wadsworth-Emmons synthesis and the ring B chromene is formed by Mukaiyama directed aldol cylisation: Michael addition completes the formation of the rotenoid at its correct oxidation state and in its stable cis-form.Examples with, and without 2,3-dimethoxylation in ring A are described.
- crombie, Leslie,Josephs, Jonathan L.
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p. 2599 - 2604
(2007/10/02)
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- 5-Thiorotenoids: A New Synthesis of General Applicability to Rotenoids
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A new synthesis of general utility for rotenoid structures is reported and applied to the specific case of 5-thiorotenoids.
- Crombie, Leslie,Josephs, Jonathan L.,Larkin, John,Weston, John B.
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p. 972 - 973
(2007/10/02)
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- AN EASY PREPARATION OF SIMPLE SULTINES AND HYDROXYALKANESULFINATE SALTS
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In accord with mechanistic prediction a one-pot, two-stage, controlled chlorination-hydrolysis of HO(CH2)nSH gave the sultine when n=3 or 4, and the polymeric sulfinic ester when n=5 or 6; alkaline hydrolysis of either product yielded the corresponding sodium ω-hydroxy-1-alkanesulfinate.
- King, J. F.,Rathore, Rajenda
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p. 2763 - 2766
(2007/10/02)
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- Synthesis and Properties of Achiral Coronands Incorporating the Sulfide and Sulfoxide Functionality
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A number of polyether coronands incorporating sulfide and sulfoxide functionality and five or six ether oxygen atoms were prepared, their formation of complexes with alkali metal and ammonium salts were studied and the results were compared with analogous
- Raguse, Burkhard,Ridley, Damon D.
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p. 1943 - 1952
(2007/10/02)
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- NEW SYNTHETIC METHODS : SODIUM ALKANECHALCOGENATES AS DEMETHYLATING AGENTS. SCOPE, LIMITATION AND NEW ONE-POT SYNTHESIS OF DIARYLDISELENIDES.
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Sodium alkanechalcogenates (S, Se) cleave the alkylarylchalcogenides (O, S, Se).The versatility of such reagents is developed and applied to a new synthesis of diaryldiselenides.
- Evers, Michel,Christiaens, Leon
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p. 377 - 380
(2007/10/02)
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