- Synthesis of long-wavelength absorbing porphyrin m-benzoic acids as molecular tectons for surface studies
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Porphyrins are becoming increasingly important building blocks in material science. This is due in part to several favorable characteristics; such as strong absorption into the infrared region, tunable electronic properties and the possibility to modify and define the porphyrin core in multiple ways. Herein we report synthetic methodologies for porphyrin-based molecular tectons for surface studies. The study aims to generate porphyrins with directional anchoring groups of different length and we report a library of long-wavelength absorbing porphyrins with a special focus on organometallic coupling reactions for the introduction of benzoic acid moieties as anchor groups.
- Meindl, Alina,Ryan, Aoife A.,Flanagan, Keith J.,Senge, Mathias O.
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Read Online
- Zinc(II)-dipicolylamine-functionalized polydiacetylene-liposome microarray: A selective and sensitive sensing platform for pyrophosphate ions
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A microarray-chip assay system for the fluorescence detection of phosphate-containing analytes in aqueous media has been constructed from stimuli-responsive polymerized poly(diacetylene)-liposomes for the first time. Proper combination of the liposome components (ZnII-dipicolylamine for phosphate binding and an amine-terminated component for anchoring the liposome onto an aldehyde-derivatized glass plate), has led to a microarray chip that selectively detects pyrophosphate, an important biomarker, over competing anions, such as phosphate and adenosine triphosphate, with nanomolar sensitivity. The chip-based assay shows advantages, such as high specificity and sensitivity, over solution-based assays that use the same liposomes, and over known homogeneous molecular sensing systems. Microchip 'N Dale: A microarray-chip system based on a poly(diacetylene) liposome functionalized with a zinc(II)-dipicolylamine ligand detects pyrophosphate ions with unparalleled sensitivity and selectivity. These chips show advantages over solution-based assays that use the same liposomes. Copyright
- Kim, Kyung Mi,Oh, Dong Ju,Ahn, Kyo Han
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- Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors
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Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novelhHDAC6 inhibitors, having low inhibitory potency overhHDAC1 andhHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with lowin vitroandin vivotoxicity. Structural analysis of 6h and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue 6h was also determined in a validated human lung model of TGF-β1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF.
- Campiani, Giuseppe,Cavella, Caterina,Osko, Jeremy D.,Brindisi, Margherita,Relitti, Nicola,Brogi, Simone,Saraswati, A. Prasanth,Federico, Stefano,Chemi, Giulia,Maramai, Samuele,Carullo, Gabriele,Jaeger, Benedikt,Carleo, Alfonso,Benedetti, Rosaria,Sarno, Federica,Lamponi, Stefania,Rottoli, Paola,Bargagli, Elena,Bertucci, Carlo,Tedesco, Daniele,Herp, Daniel,Senger, Johanna,Ruberti, Giovina,Saccoccia, Fulvio,Saponara, Simona,Gorelli, Beatrice,Valoti, Massimo,Kennedy, Breándan,Sundaramurthi, Husvinee,Butini, Stefania,Jung, Manfred,Roach, Katy M.,Altucci, Lucia,Bradding, Peter,Christianson, David W.,Gemma, Sandra,Prasse, Antje
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p. 9960 - 9988
(2021/07/31)
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- Carbamate as an accelerating group in intermolecular Pauson-Khand reaction
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The Pauson-Khand reaction (PKR) is a powerful means for the construction of cyclopentenones. However, its applications have been limited to the intramolecular version of this reaction because poor yield and regioselectivity are often the major problems in intermolecular PKR. Here we describe that a carbamate moiety in alkene substrate accelerates this intermolecular PKR. The reaction of N-4-dimethylaminophenyl O-allyl carbamate with alkyne-cobalt complex gave cyclopentenones in high yield (up to 90%) and regioselectivity (>9:1).
- Asano, Shota,Itto-Nakama, Kaori,Arimoto, Hirokazu
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supporting information
(2020/05/05)
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- QSAR and molecular docking studies of the inhibitory activity of novel heterocyclic GABA analogues over GABA-AT
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We have previously reported the synthesis, in vitro and in silico activities of new GABA analogues as inhibitors of the GABA-AT enzyme from Pseudomonas fluorescens, where the nitrogen atom at the γ-position is embedded in heterocyclic scaffolds. With the goal of finding more potent inhibitors, we now report the synthesis of a new set of GABA analogues with a broader variation of heterocyclic scaffolds at the γ-position such as thiazolidines, methyl-substituted piperidines, morpholine and thiomorpholine and determined their inhibitory potential over the GABA-AT enzyme from Pseudomonas fluorescens. These structural modifications led to compound 9b which showed a 73% inhibition against this enzyme. In vivo studies with PTZ-induced seizures on male CD1 mice show that compound 9b has a neuroprotective effect at a 0.50 mmole/kg dose. A QSAR study was carried out to find the molecular descriptors associated with the structural changes in the GABA scaffold to explain their inhibitory activity against GABA-AT. Employing 3D molecular descriptors allowed us to propose the GABA analogues enantiomeric active form. To evaluate the interaction with Pseudomonas fluorescens and human GABA-AT by molecular docking, the constructions of homology models was carried out. From these calculations, 9b showed a strong interaction with both GABA-AT enzymes in agreement with experimental results and the QSAR model, which indicates that bulky ligands tend to be the better inhibitors especially those with a sulfur atom on their structure.
- Rodríguez-Lozada, Josué,Tovar-Gudi?o, Erika,Guevara-Salazar, Juan Alberto,Razo-Hernández, Rodrigo Said,Santiago, ángel,Pastor, Nina,Fernández-Zertuche, Mario
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- C(alkenyl)-H Activation via Six-Membered Palladacycles: Catalytic 1,3-Diene Synthesis
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A catalytic method to prepare highly substituted 1,3-dienes from two different alkenes is described using a directed, palladium(II)-mediated C(alkenyl)-H activation strategy. The transformation exhibits broad scope across three synthetically useful substrate classes masked with suitable bidentate auxiliaries (4-pentenoic acids, allylic alcohols, and bishomoallylic amines) and tolerates internal nonconjugated alkenes, which have traditionally been a challenging class of substrates in this type of chemistry. Catalytic turnover is enabled by either MnO2 as the stoichiometric oxidant or co-catalytic Co(OAc)2 and O2 (1 atm). Experimental and computational studies were performed to elucidate the preference for C(alkenyl)-H activation over other potential pathways. As part of this effort, a structurally unique alkenylpalladium(II) dimer was isolated and characterized.
- Liu, Mingyu,Yang, Pusu,Karunananda, Malkanthi K.,Wang, Yanyan,Liu, Peng,Engle, Keary M.
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supporting information
p. 5805 - 5813
(2018/05/14)
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- Aerobic Photooxidative Synthesis of β-Alkoxy Monohydroperoxides Using an Organo Photoredox Catalyst Controlled by a Base
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Transition-metal-free synthesis of β-alkoxy monohydroperoxides via aerobic photooxidation using an acridinium photocatalyst was developed. This method enables the synthesis of some novel hydroperoxides. The peroxide source is molecular oxygen, which is cost-effective and atomically efficient. Magnesium oxide plays an important role as a base in the catalytic system.
- Asano, Yuya,Nagasawa, Yoshitomo,Yamaguchi, Eiji,Itoh, Akichika
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supporting information
p. 409 - 412
(2018/02/21)
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- Tridentate Directing Groups Stabilize 6-Membered Palladacycles in Catalytic Alkene Hydrofunctionalization
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Removable tridentate directing groups inspired by pincer ligands have been designed to stabilize otherwise kinetically and thermodynamically disfavored 6-membered alkyl palladacycle intermediates. This family of directing groups enables regioselective remote hydrocarbofunctionalization of several synthetically useful alkene-containing substrate classes, including 4-pentenoic acids, allylic alcohols, homoallyl amines, and bis-homoallylamines, under Pd(II) catalysis. In conjunction with previous findings, we demonstrate regiodivergent hydrofunctionalization of 3-butenoic acid derivatives to afford either Markovnikov or anti-Markovnikov addition products depending on directing group choice. Preliminary mechanistic and computational data are presented to support the proposed catalytic cycle.
- O'Duill, Miriam L.,Matsuura, Rei,Wang, Yanyan,Turnbull, Joshua L.,Gurak, John A.,Gao, De-Wei,Lu, Gang,Liu, Peng,Engle, Keary M.
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supporting information
p. 15576 - 15579
(2017/11/14)
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- Repeated dosing with NCX1404, a nitric oxide-donating pregabalin, re-establishes normal nociceptive responses in mice with streptozotocin-induced painful diabetic neuropathy
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NCX1404 [(3S)-5-methyl-3-(((1-(4-(nitrooxy)butanoyloxy)ethoxy) carbonylamino) methyl)hexanoic acid] is a novel nitric oxide (NO)-donating pregabalin that is readily absorbed and processed in vivo to pregabalin and NO. We determined the antiallodynic response of NCX1404 after acute or after 7, 14, and 21 days of repeated daily oral dosing in mice with streptozotocin (STZ)-induced painful diabetic neuropathy (PDN). Pregabalin and its combination with the NO donor isosorbide mononitrate (ISMN) were used for comparison. The blood levels of pregabalin and nitrites, used as surrogate marker of NO release, after NCX1404 or pregabalin dosing were monitored in parallel experiments using liquid chromatography with tandem mass spectrometry (LC-MS/MS). NCX1404 and pregabalin resulted in similar pregabalin levels as it was their antiallodynic activity after acute dosing in STZ mice. However, NCX1404 resulted in disease-modifying properties when administered daily for 21 days, as indicated by the time- and dose-dependent reversal of STZ-induced mechanical allodynia (paw withdrawal threshold [PWT]Veh-21d = 1.3 v 0.15 g for vehicle; PWTNCX1404-21d = 1.4 ± 0.5 g, 2.9 ± 0.2 g? and 4.1 ± 0.2 g?, respectively for 19, 63, and 190 μmol/kg, oral gavage [PO] of NCX1404; ?P, 0.05 versus vehicle). This effect was not shared by pregabalin at equimolar doses (190 μmol/kg, PO, PWTPregab-21d = 1.4 ± 0.1 g?, ?P Veh-7d= 1.7 ± 0.16 g; PWTISMN-7d = 3.9 ± 0.34 g?; PWTPregab-7d = 1.3 ± 0.07 g; PWTISMN+pregab-7d = 3.8 ± 0.29 g?; ?P, 0.05) but not at later time points. The long-term effect of NCX1404 was independent of residual drug exposure and lasted for several days after the treatment was stopped. In summary, like pregabalin, NCX1404 is an effective antiallodynic agent. Differently from pregabalin, repeated dosing of NCX1404 re-established normal nociceptive responses in STZ-induced PDN in mice.
- Varani, Katia,Vincenzi, Fabrizio,Targa, Martina,Ravani, Annalisa,Bastia, Elena,Storoni, Laura,Brambilla, Stefania,Almirante, Nicoletta,Impagnatiello, Francesco
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p. 240 - 247
(2016/04/26)
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- Synthesis of polysiloxane-based quaternized imidazolium salts with a hydroxy group at the end of alkyl groups
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A series of polysiloxane derivatives having quaternized imidazolium moieties with hydroxyalkyl groups ([HPImnOH]Xs) (where n is the number of methylene group and X is counter anion) were prepared by quaternization of poly(3-chloropropylmethylsiloxane) (P1) using 1-(ω-hydroxyalkyl)imidazole derivatives (ImnOHs) and anion-exchange reaction using lithium bis(trifluoromethanesulfonyl)imide. Polysiloxane-based quaternized imidazolium salts having hydroxyalkyl groups with chloride anion ([HPImnOH]Cls) were obtained with high quaternization ratio of approximately 100 mol%. The glass transition temperatures (Tgs) of [HPImnOH]Xs were reduced by introducing a hydroxy group at the end of alkyl groups; however, no significant reduction in Tgs was observed by anion exchange from chloride anion to bis(trifluoromethanesulfonyl)imide one (Tf2N-).
- Ichikawa, Tsukasa,Wako, Tsuyoshi,Nemoto, Nobukatsu
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- Synthesis and anticancer properties of RGD peptides conjugated to nitric oxide releasing functional groups and abiraterone
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A series of analogues of the integrin binding aspartic acid-glycine-arginine (RGD) peptide sequence were synthesised conjugated to nitric oxide (NO) donating functional groups. Also the cytotoxicity of abiraterone, a prostate cancer drug, was explored when it was conjugated in three part constructs to RGD sequences and NO releasing heterocycles. In general the analogues showed integrin binding affinity comparable to RGD reference compounds, and all released NO by the Griess test assay. Two analogues exhibited significant cytotoxic effects against PC3 and MCF7 cell lines.
- Nortcliffe, Andrew,Fleming, Ian N.,Botting, Nigel P.,O'Hagan, David
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supporting information
p. 8343 - 8347
(2015/03/05)
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- The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase
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A novel class of podophyllotoxin derivatives have been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities towards histone deacetylases and Topo II and their cytotoxicities in cancer cell lines were evaluated. The aromatic capping group connection, linker length and zinc-binding group were systematically varied and preliminary conclusions regarding structure-activity relationships are discussed. Among all of the synthesized hybrid compounds, compound 24d showed the most potent HDAC inhibitory activity at a low nanomolar level and exhibited powerful antiproliferative activity towards HCT116 colon carcinoma cells at a low micromolar level. Further exploration of this series led to the discovery of potent dual inhibitor 32, which exhibited the strongest in vitro cytotoxic activity.
- Zhang, Xuan,Bao, Bin,Yu, Xiuhua,Tong, Linjiang,Luo, Yu,Huang, Qingqing,Su, Mingbo,Sheng, Li,Li, Jia,Zhu, Hong,Yang, Bo,Zhang, Xiongwen,Chen, Yi,Lu, Wei
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p. 6981 - 6995
(2013/11/06)
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- Enantioselective bromolactonization of cis-1,2-disubstituted olefinic acids using an amino-thiocarbamate catalyst
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A facile, highly regio- and enantioselective amino-thiocarbamate-catalyzed bromolactonization of cis-1,2-disubstituted olefinic acids has been developed. The use of the enantio-enriched lactones in the synthesis of chiral synthetic intermediates is also demonstrated. 2012
- Tan, Chong Kiat,Le, Chencheng,Yeung, Ying-Yeung
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supporting information; experimental part
p. 5793 - 5795
(2012/08/08)
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- NITRIC OXIDE RELEASING COMPOUNDS FOR THE TREATMENT OF NEUROPHATIC PAIN
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The present invention relates to nitric oxide releasing derivatives of serotonin norepinephrine reuptake inhibitors and their use for the treatment of pain, having the following general formula (I) or pharmaceutically acceptable salts thereof: wherein : A is selected from the formulas (1a) and (1b). The present invention also relates to pharmaceutical formulation comprising such derivatives, to a process for their preparation and to intermediates useful for their preparation.
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Page/Page column 75-76
(2011/08/21)
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- NITRIC OXIDE RELEASING COMPOUNDS FOR THE TREATMENT OF NEUROPATHIC PAIN
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The invention relates to nitrooxyderivatives of Gamma- aminobutyric acid analogs (GABA analogs) for treating neuropathic pain and in particular diabetic neuropathy. The invention also relates to pharmaceutical formulation comprising such derivatives, to a process for their preparation.
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Page/Page column 55
(2011/09/19)
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- Peptide ligation assisted by an auxiliary attached to amidyl nitrogen
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New thiol-containing auxiliaries were developed for peptide ligation. They were placed at the amidyl N-atom in the second amino acid residue of a peptide fragment. With the new auxiliaries, peptide ligation could be conducted at non-Cys and non-Gly sites. Compared to other recently developed auxiliaries, an important feature of the present design was that the new auxiliaries were generally applicable and readily removable.
- Li, Juan,Cui, Hong-Kui,Liu, Lei
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scheme or table
p. 1793 - 1796
(2010/06/13)
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- NOVEL BENZODIAZEPINE DERIVATIVES
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The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 153
(2010/08/18)
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- Rotamers of palladium complexes bearing IR active N-heterocyclic carbene ligands: Synthesis, structural characterization and catalytic activities
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The preparation and properties of mono- versus bis(carbene) Pd(II) complexes bearing unsymmetrical cyano- and ester-functionalized NHC ligands as potential IR probes were studied in detail. Direct reaction of Pd(OAc)2 with functionalized imidazolium salts afforded either bis(carbene) (3a, c) or monocarbene complexes (5, 6) with a N-coordinated imidazole co-ligand. The latter were exclusively obtained with N-ethylene substituted salts, which were found to undergo N-C cleavage reaction. The milder Ag-carbene transfer reaction on the other hand was tolerable to the length of the substituents and the nature of the functional groups. All bis(carbene) complexes (3a-c, 4a-c) were obtained as a inseparable mixture of square-planar trans-anti and trans-syn rotamers. The identity, ratio and dynamic equilibrium of these rotamers have been investigated and the relatively high rotational barrier for rotamers of 3a was estimated to be about 74 kJ mol-1 at 380 K. All eight complexes were fully characterized by NMR and IR spectroscopies, ESI mass spectrometry and X-ray single crystal and powder diffraction. A preliminary catalytic study showed that ester-functionalized complexes 4a and 4b gave rise to highly active catalyst in the double Mizoroki-Heck coupling of aryl dibromides, while the in situ ester-hydrolyzed complexes were also active in the coupling of activated aryl chlorides.
- Huynh, Han Vinh,Wu, Jiang
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supporting information; experimental part
p. 323 - 331
(2009/04/13)
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- High-throughput synthesis of azide libraries suitable for direct "click" chemistry and in situ screening
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A key challenge in current drug discovery is the development of high-throughput (HT) amenable chemical reactions that allow rapid synthesis of diverse chemical libraries of enzyme inhibitors. The Cu(I)-catalyzed, 1,3-dipolar cycloaddition between an azide and an alkyne, better known as "click chemistry", is one such method that has received the most attention in recent years. Despite its popularity, there is still a lack of robust and efficient chemical strategies that give access to diverse libraries of azide-containing building blocks (key components in click chemistry). We report herein a highly robust and efficient strategy for high-throughput synthesis of a 325-member azide library. The method is highlighted by its simplicity and product purity. The utility of the library is demonstrated with the subsequent "click" synthesis of the corresponding bidentate inhibitors against PTP1B.
- Srinivasan, Rajavel,Tan, Lay Pheng,Wu, Hao,Yang, Peng-Yu,Kalesh, Karunakaran A.,Yao, Shao Q.
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supporting information; experimental part
p. 1821 - 1828
(2009/06/28)
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- The preparation and utility of bis(sulfinyl)imidoamidine ligands for the copper-catalyzed Diels-Alder reaction
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The design and preparation of a novel class of ligands based on the sulfinyl imine functionality is described. In particular, an efficient and modular synthesis of bis(sulfinyl)imidoamidine (siam) ligands is reported. The versatility of the synthetic sequence is demonstrated by the preparation of various analogues to explore the effect of substitution about the ligand framework on catalytic activity. The utility of the siam ligands in asymmetric catalysis is demonstrated in the Cu(II)-catalyzed Diels-Alder reaction where highly enantio- and diastereoselective reactions are reported for a range of N-acyloxazolidinone dienophile and diene substrate combinations. Of particular note is the efficiency of these asymmetric catalysts for reactions involving challenging and relatively unreactive acyclic diene substrates. Finally, structural data are provided for several ligands as well as metal-ligand complexes.
- Owens, Timothy D.,Souers, Andrew J.,Ellman, Jonathan A.
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- Method for synthesizing oxazinones
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New methods and intermediates are discussed for the stereospecific synthesis of oxazinone compounds.
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- Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones
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Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride - alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one.
- Wolfe, Saul,Wilson, Marie-Claire,Cheng, Ming-Huei,Shustov, Gennady V.,Akuche, Christiana I.
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p. 937 - 960
(2007/10/03)
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- A mild and effective method for the transesterification of carboxylic acid esters
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An extraordinarily versatile transesterification of simple or highly functionalized esters of aliphatic and aromatic carboxylic acids in high yields is catalyzed by dibutyltin oxide [Eq. (1)]. The reaction is compatible with several functional groups, for example, acetals, ketals, aliphatic bromides, enol ethers, urethanes, as well as free hydroxy, phenolic, and amino groups, and even with water.
- Baumhof, Patrick,Mazitschek, Ralph,Giannis, Athanassios
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p. 3672 - 3674
(2007/10/03)
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- Total synthesis of marine oxylipin bacillariolides I-III
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Marine oxylipin bacillariolides I-III were synthesized from (R)-malic acid, using diastereoselective one-pot formation of the chiral cyclopentane derivative from the anion of allyl phenyl sulfone and chiral epoxymesylate as the key reaction. (C) 2000 Elsevier Science Ltd.
- Miyaoka, Hiroaki,Tamura, Masahide,Yamada, Yasuji
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p. 8083 - 8094
(2007/10/03)
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- Magnesium Methyl Carbonate-Activated Alkylation of Methyl Ketones with an ω-Halo Nitrile, Esters, and Amides
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Terminally substituted, extended-chain derivatives of the 2-dibenzofuranyl methyl ketone 6 and its phenylethyl analogue 12 were readily obtained by converting the ketones to magnesium chelates of their β-carboxylated enolates with magnesium methyl carbonate (MMC, methyl methoxymagnesium carbonate, Stiles's reagent), followed by alkylation in situ with ω-halo compounds, X(CH2)n where X = Br and Y = CO2Me, ON, CONMe2, CON(i-Pr)2, CON(CH2)4, or CON(CH2)5 for n = 1; X = Br or I, and Y = CO2Me for n = 2; and X = Br and Y = CO2Me for n = 3. Dimethykarbamoyl chloride (n = 0) gave products derived from MMC and the solvent, N,N-dimethylformamide. The order of reactivity of the halides was α > β > γ and β-I > β-Br. β-Bromo amides were found to be unsuitable reactants. Lower reaction temperatures favored alkylation over competing elimination of HX from methyl β-halopropionate. No self-condensation products of the ketones were observed; however, bis-alkylation and monomethylation products were formed when reaction times were prolonged. In contrast to the unsubstituted β-keto acid 13, all intermediate α-alkyl β-keto acids decarboxylated during the reaction or the workup.
- Hand, Elli S.,Johnson, Stephen C.,Baker, David C.
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p. 1348 - 1355
(2007/10/03)
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- Studies on the Synthesis of Mavacurine-Type Indole Alkaloids. First Total Synthesis of (+/-)-2,7-Dihydropleiocarpamine
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Closure of the six-membered C ring of pentacyclic mavacurine-type alkaloids from suitably substituted tetracyclic substructures embodying rings ABDE of these alkaloids, either by electrophilic cyclization upon the indole 3-position or by intramolecular alkylation of the piperidine nitrogen, failed.In contrast, 6a-homopleiocarpamine (45) has been synthesized from dithioacetal 42 by an electrophilic cyclization involving the closure of the seven-membered C ring.The first total synthesis of the alkaloid 2,7-dihydropleiocarpamine (58) has been achieved by photocyclization of the tetracyclic chloroacetamide 54 as the key step.The required tetracyclic ABDE ring systems were prepared by a straightforward sequence consisting of nucleophilic addition of a 1-indoleacetatic ester enolate to the γ position of a pyridinium salt, acid cyclization of the resulting 1,4-dihydropyridine, and final elaboration of the (E)-ethylidene substituent.An alternative synthesis of the tetracyclic alkaloid vinoxine (10a) is also reported.
- Bennasar, M.-Lluisa,Zulaica, Ester,Jimenez, Juan-Miguel,Bosch, Joan
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p. 7756 - 7767
(2007/10/02)
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- Synthesis of Methyl Esters by Titanate-catalyzed Transesterifications
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The low solubility of tetramethyl titanate has so far prevented the laboratory use of titanate-catalyzed transesterifications with formation of methyl esters.Two procedures are described here, which allow the application of this exceedingly mild method to the synthesis of methyl esters: one uses methyl propionate/Ti(OEt)4, the other one uses methanol/Gly-Ti, a new type of catalyst, prepared from Ti(OEt)4/ethylene glycol 2:1.
- Schnurrenberger, Peter,Zueger, Max F.,Seebach, Dietrich
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p. 1197 - 1201
(2007/10/02)
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- Synthesis of 7,8,9,10,11,12,20,21,22,23,24,25-Dodecahydrodibenzotetraoxacyclodocosin, a Crown Ether
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A number of symmetrical diesters and an unsymmetrical type have been synthesised from pyrocatechol.Under conditions in which intramolecular acyloin formation was anticipated the product from one symmetrical compound, ethyl 4-(o-ethoxycarbonylpropoxyphenoxy)butyrate, was a cyclic bis-β-keto-ester resulting in reasonable yield from intermolecular Dieckmann cyclisation.Hydrolysis to the 9,22 diketone, and its reduction to 7,8,9,10,11,12,20,21,22,23,24,25-dodecahydrodibenzotetraoxacyclodocosin 'dibenzo-22-crown-4', proceeded smoothly.An unsymmetrical intermediate, methyl 4-(o-ethoxycarbonylmethoxypropylphenoxy)butyrate, was prepared for similar cyclisation and in preliminary experiments appeared to give acyloin and β-keto-ester products.The method represents a different approach to crown ether systems of certain types.
- Tyman, John H. P.,Grundy, Jesse,Brown, George R.
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p. 336 - 343
(2007/10/02)
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- Synthesis of Cannabinoid Model Compounds. Part 2): (3R,4R)-δ1(6)-Tetrahydrocannabinol-5"-oic Acid and 4"(R,S)-Methyl-(3R,4R)-δ1(6)-Tetrahydrocannabinol-5"-oic Acid
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Two novel cannabinoid model compounds, (3R,4R)-Δ1(6)-tetrahydrocannabinol-5"-oic acid (22) and 4"(R,S)-methyl-(3R,4R)-Δ1(6)-tetrahydrocannabinol-5"-oic acid (23) were synthesized by acid-catalyzed condensation of (+)-trans-p-mentha-2,8-dien-1-ol (1) with the substituted resorcinols 18 and 19 obtained by a Wittig reaction between 3,5-bis(benzyloxy)benzaldehyde (7) and methyl 4-bromobutanoate (10) or methyl 4-bromo-2(R,S)-methylbutanoate (11) resp. with subsequent hydrogenation.The resulting methyl esters 20 and 21 were hydrolyzed to give acids 22 and 23.
- Franke, Ingo,Binder, Michael
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p. 2508 - 2514
(2007/10/02)
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- Process for the production of even series ω-amino acids
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The invention relates to a process for the production of even-series ω-amino acids of the general empirical formula NH2 (CH2 CH2)n CH2 COOH /I/, where N = 1 or 2. The process of the invention comprises telomerizing ethylene with methyl esters of halogen acetic acids of the general empirical formula Xm CH3-m COOCH3 /II/, where X = Br and m = 1 or X = Cl and m = 2 or 3, at a temperature of from 100 to 145° C. and under ethylene pressure of from 25 to 40 gage atmospheres in the presence of initiators of free-radical reactions. The telomerization procedure gives telomers of the general empirical formula CH3 OOCCH3-m Xm-1 (CH2 CH2)n X /III/, where X, n and m are as in formulas /I/ and /II/. In case X = Br and m = 1, the telomers described by formula /III/ are subjected to ammonolysis with ammonia at a temperature of about 100° C to yield ammonolysis products; whereas, in case X = Cl and m = 2 or 3, the telomers described by formula /III/ are reduced to telomers of the same general formula, where X = Cl and m = 1, and the latter are subjected to ammonolysis with ammonia at a temperature from 135° to 140° C to yield ammonolysis products. Then the ammonolysis products are hydrolyzed with hydrochloric acid at a temperature of from 80° to 90° C., and the desired product is recovered from the resultant hydrolyzate by use of a styrene-divinylbenzene sulfocationite resin in the H form. The foregoing process uses widely available industrial raw materials, proceeds by a straightforward route and requires simple equipment; it is further characterized by high yields at all steps; all unreacted feedstocks can be completely recycled; and no non-utilizable wastes are produced.
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