- Stereoselective Synthesis of Carbobicyclics via Organoyttrium-Catalyzed Sequential Cyclization/Silylation Reactions
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The sequential cyclization/silylation of 1,5-dienes and 1,6-dienes was effected under mild reaction conditions using catalytic quantities of Cp2*YMe-THF. The process provides carbobicyclics in high yields and with excellent selectivities. The active catalyst is postulated to be Cp2*YH-THF, which is generated in situ. A variety of alkenyl-substituted cyclopentane and cyclohexane substrates were examined. The high diastereoselectivities apparently originate from a preference for a chairlike transition structure that minimizes unfavorable steric interactions between the bulky Cp* ligands of the catalyst and the preexisting ring of the substrate. Acyclic triene precursors, 4-ethenyl-substituted 1,5-heptadienes and 5-ethenyl-substituted 1,8-nonadienes were also examined. These triene substrates, when exposed to the cyclization/silylation protocol, provide the strained trans-bicyclo[3.3.0]octanes and trans-decalin systems in high yield with excellent diastereoselectivity. The high selectivity is again attributed to the preference for a chairlike transition structure. The cyclized organosilane products isolated from these reactions were easily converted to the more versatile alcohols utilizing known oxidation methods.
- Molander, Gary A.,Nichols, Paul J.,Noll, Bruce C.
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- Exploiting sequential lipase-catalyzed reactions to achieve enantiomerically pure chiral primary alcohols
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The lipase-catalyzed enantioselective acetylation of benzofused cycloalkane-containing primary alcohols with vinyl acetate was performed and allowed the isolation of enantiopure alcohols. Lipases from P. cepacia, C. rugosa, C. antarctica, P. fluorescens, C. cylindracea and M. miehei exhibited remarkable activity towards acetylation of these alcohols, affording the corresponding acetates with high conversion. Due to the high lipase activity toward primary alcohols, the enantioselectivity was low. To circumvent this problem, sequential kinetic resolution was employed with enantiocomplementary lipases leading to enantiomerically pure primary alcohols. This method represents a new approach to obtain chiral building blocks bearing ring systems, such as indanes, chromanes and tetralins.
- Martins, Rodrigo S.,Ahmad, Anees,Silva, Luiz F.,Andrade, Leandro H.
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Read Online
- Palladium/TY-Phos-Catalyzed Asymmetric Intermolecular α-Arylation of Aldehydes with Aryl Bromides
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Despite much progress has been made in the asymmetric α-arylation reactions of cyclic ketones, lactones and lactams, the enantioselective α-arylation of acyclic carbonyl compounds lagged much behind due to the in situ generated Z/E-enolate intermediates l
- Li, Wenbo,Liu, Feng,Pan, Zhangjin,Wu, Hai-Hong,Zhang, Junliang,Zhu, Shuai
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supporting information
p. 18542 - 18546
(2021/07/21)
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- Functional Group Interconversion of Alkylidenemalononitriles to Primary Alcohols by a Cooperative Redox Operation
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Functional group interconversions are essential chemical processes enabling synthesis. In this report, we describe a strategy to convert alkylidenemalononitriles into primary alcohols in one step. The reaction relies on a choreographed redox process invol
- Emmetiere, Fabien,Grenning, Alexander J.
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p. 3077 - 3085
(2020/08/10)
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- Visible-Light-Mediated Anti-Markovnikov Hydration of Olefins
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Considering that stoichiometric borane and oxidant are required in the classical alkene anti-Markovnikov hydration process, it remains appealing to achieve the transformation in a catalytic protocol. Herein, a visible-light-mediated anti-Markovnikov addition of water to alkenes by using an organic photoredox catalyst in conjunction with a redox-active hydrogen atom donor was developed, which avoided the need for a transition-metal catalyst, stoichiometric borane, as well as oxidant. Both terminal and internal olefins are readily accommodated in this transformation to obtain corresponding primary and secondary alcohols in good yields with single regioselectivity. This procedure can be scaled up to gram scale with a 230 turnover number based on photocatalyst.
- Hu, Xia,Zhang, Guoting,Bu, Faxiang,Lei, Aiwen
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p. 1432 - 1437
(2017/08/09)
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- Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators
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Pharmacological modulation of the transient receptor potential melastatin type 8 (TRPM8) is currently under investigation as a new approach for the treatment of pain and other diseases. In this study, a series of N-substituted tryptamines was prepared to explore the structural requirements determining TRPM8 modulation. Using a fluorescence-based screening assay, we identified two compounds acting as an activator (2-(1H-indol-3-yl)-N-(4-phenoxybenzyl)ethanamine, 21) or an inhibitor (N,N-dibenzyl-2-(1H-indol-3-yl)ethanamine, 12) of calcium influx in HEK293 cells. In patch-clamp recordings, compound 21 displayed a significantly higher potency (EC50 = 40 ± 4 μM) and a similar efficacy when compared to menthol; by contrast, compound 12 produced a concentration-dependent inhibition of menthol-induced TRPM8 currents (IC50 = 367 ± 24 nM). Molecular modeling studies using a homology model of a single rat TRPM8 subunit identified a putative binding site located between the VSD and the TRP box, disclosing differences in the binding modes for the agonist and the antagonist.
- Bertamino, Alessia,Ostacolo, Carmine,Ambrosino, Paolo,Musella, Simona,Di Sarno, Veronica,Ciaglia, Tania,Soldovieri, Maria Virginia,Iraci, Nunzio,Fernandez Carvajal, Asia,De La Torre-Martinez, Roberto,Ferrer-Montiel, Antonio,Gonzalez Muniz, Rosario,Novellino, Ettore,Taglialatela, Maurizio,Campiglia, Pietro,Gomez-Monterrey, Isabel
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p. 2179 - 2191
(2016/03/25)
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- Oxidative rearrangement of alkenes using in situ generated hypervalent iodine(III)
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A novel protocol for the oxidative rearrangement of alkenes using in situ generated hypervalent iodine(III) was developed. This approach uses inexpensive, readily available, and stable chemicals (PhI, mCPBA, and TsOH) giving rearrangement products in yields comparable to those obtained using the more expensive commercially available [hydroxy(tosyloxy)iodo]benzene [HTIB or Koser's reagent]. Additionally, an alternative protocol for the synthesis of 1-methyl-2-tetralone through the one-step epoxidation/rearrangement of 4-methyl-1,2-dihydronaphthalene using mCPBA and TsOH was developed.
- Ahmad, Anees,Scarassati, Paulo,Jalalian, Nazli,Olofsson, Berit,Silva Jr., Luiz F.
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p. 5818 - 5820
(2013/10/01)
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- COLCHICINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, METHOD FOR PREPARING SAID DERIVATIVES, AND PHARMACEUTICAL COMPOSITION COMPRISING SAID DERIVATIVES
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The present invention relates to colchicine derivatives expressed in chemical formula 1, or to pharmaceutically acceptable salts thereof, to a method for preparing said derivatives, and to a pharmaceutical composition comprising said derivatives. The colchicine derivatives according to the present invention exhibit superior immunomodulatory effects as compared with conventional immunomodulators or colchicines, and therefore can be valuably used as an immunomodulator for modulating an acute or chronic immune response in organ transplantation.
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Paragraph 0092; 0093; 0094; 0095
(2013/03/26)
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- COLCHICINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, METHOD FOR PREPARING SAID DERIVATIVES, AND PHARMACEUTICAL COMPOSITION COMPRISING SAID DERIVATIVES
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The present invention relates to colchicine derivatives expressed in chemical formula 1, or to pharmaceutically acceptable salts thereof, to a method for preparing said derivatives, and to a pharmaceutical composition comprising said derivatives. The colchicine derivatives according to the present invention exhibit superior immunomodulatory effects as compared with conventional immunomodulators or colchicines, and therefore can be valuably used as an immunomodulator for modulating an acute or chronic immune response in organ transplantation.
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Paragraph 0059; 0060; 0061; 0062
(2013/03/26)
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- Synthesis of alcohols via a rhodium-catalyzed hydroformylation-reduction sequence using tertiary bidentate amine ligands
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The synthesis of alcohols from aromatic olefins is described using a rhodium-catalyzed hydroformylation-reduction sequence with the assistance of a tertiary diamine ligand. The alcohols are produced in excellent branched to linear ratios and in good to excellent isolated yields. In all cases no aldehyde product, from hydroformylation, or alkyl product, from olefin reduction, was detected. Copyright
- Cheung, Lawrence L. W.,Vasapollo, Giuseppe,Alper, Howard
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supporting information; experimental part
p. 2019 - 2022
(2012/09/22)
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- Synthesis and biological activity of both enantiomers of kujigamberol isolated from 85-million-years-old Kuji amber
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The full-structure of a norlabdane terpenoid, kujigamberol (1) was determined by total synthesis. Key features of the total synthesis are (1) installation of isopentyl group through an o-lithiation of benzamide, (2) construction of tetralone by the RCM reaction, and (3) optical resolution of (±)-1 using chromatographical separation of the corresponding camphanates. X-ray crystallographical analysis of p-bromobenzoate obtained from the more polar camphanate that was identical with a natural derivative, revealed natural kujigamberol to have an S-configuration. Both the natural enantiomer and its (R)-antipode showed the same inhibitory activity toward the mutant yeast and HL-60 cells, while simple analogs without alkyl groups at the C-8 and 9 positions of (±)-1 had no such activity.
- Ye, Yue Qi,Koshino, Hiroyuki,Hashizume, Daisuke,Minamikawa, Yuki,Kimura, Ken-Ichi,Takahashi, Shunya
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p. 4259 - 4262
(2012/09/22)
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- 2-substituted-(2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1- yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 1. Effects of alkyl, arylalkyl, and diarylalkyl substitution
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In this paper, we describe the synthesis of a series of α-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into an antagonist. All of the compounds were prepared and tested as a aeries of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [3H]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial. The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.010 μM in the [3H]Glu binding assay, was 52-fold more potent than 2, whose IC50 was 0.47 μM.
- Ornstein, Paul L.,Bleisch, Thomas J.,Arnold, M. Brian,Wright, Rebecca A.,Johnson, Bryan G.,Schoepp, Darryle D.
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p. 346 - 357
(2007/10/03)
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- The use of nafion-h to promote epoxide cyclizations
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Nafion-H is shown to be an effective promoter of epoxide cyclizations to aromatic positions. The reactions can be done by passing a solution of the epoxide through a column packed with Nafion-H, or by stirring a mixture of the compound with the acidic pro
- Taylor, Stephen K.,Dickinson, Michael G.,May, Scott A.,Pickering, Dacia A.,Sadek, Paul C.
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p. 1133 - 1136
(2007/10/03)
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- HYDROFORMYLATION OF TRICARBONYL(η-STYRENE)CHROMIUM AND RELATED COMPOUNDS
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Hydroformylation of the tricarbonylchromium derivatives of styrene, indene, and dihydronaphthalene using rhodium-based catalysts gives α-arylaldehydes with high regioselectivity and, using appropriate chiral catalysts, with enantiomeric excesses of up to
- Doyle, Michael M.,Jackson, Roy W.,Perlmutter, Patrick
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p. 5357 - 5360
(2007/10/02)
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- Friedel-crafts cyclialkylations of some epoxides. 2. Stereospecificity, substituent, product, and kinetic studies
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The relative facility of the cyclialkylation of several arylalkyl epoxides was investigated. Stereochemical studies on the cyclialkylation of cis- and trans-2,3-epoxy-5-phenylpentane establish that the stereospecificity of ring formation is as high as 97%
- Taylor, Stephen K.,Davisson, Mark E.,Hissom Jr., B. Rolf,Brown, Sandra L.,Pristach, Holle A.,Schramm, Scott B.,Harvey, Suzanne M.
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p. 425 - 429
(2007/10/02)
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- Friedel-Crafts Cyclialkylations of Some Epoxides
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Several arylalkyl epoxides (1-9) were investigated for cyclialkylation reactions.Cyclialkylation to form six-membered rings was observed (up to 91 percent isolated yields) at secondary but not at primary epoxide positions.Cyclialkylation was not observed with 4-phenyl-1,2-epoxybutane, but a m-methoxy substituent did promote ring closure to the primary position in moderate yield.Cyclialkylation to seven-membered rings occurred at a secondary position in reasonable yields; less rearrangement occured with the epoxide system than with analogous alkylating agents such as phenylalk yl alcohols.Reduced skeletal rearrangement is characteristic of cyclization reactions that occur with epoxides and suggests that the epoxide serves to moderate electrophilic reactivity.Cyclialkylation to form five-membered rings was not observed with epoxides that were capable of ring-opening at primary or secondary positions.
- Taylor, Stephen K.,Hockerman, Gregory H.,Karrick, Gregory L.,Lyle, Stephen B.,Schramm, Scott B.
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p. 2449 - 2452
(2007/10/02)
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