- Mg-promoted regioselective carbon-silylation of α-phosphorylacrylate derivatives
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Treatment of aromatic α-phosphorylacrylate derivatives 1a-h with Mg turnings in the presence of trimethylsilyl chloride brought about facile and regioselective C-silylation to give the corresponding β-silylated phosphonates 2a-h in excellent yields. The r
- Kyoda, Makoto,Yokoyama, Takamichi,Kuwahara, Takeshi,Maekawa, Hirofumi,Nishiguchi, Ikuzo
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Read Online
- Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho-Quinodimethane Intermediates
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The metalloradical activation of ortho-benzallylaryl N-tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single-electron reactivity of the redox non-innocent carbene intermediate. This method offers a novel route to prepare eight-membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective Ccarbene?Caryl cyclization. The desired eight-membered-ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to CoIII–carbene radical intermediates followed by dissociation of an ortho-quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical-type intermediates was confirmed by trapping experiments.
- te Grotenhuis, Colet,van den Heuvel, Naudin,van der Vlugt, Jarl Ivar,de Bruin, Bas
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supporting information
p. 140 - 145
(2017/12/13)
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- Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase
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Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS), a highly conserved pyridoxal 5′-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of moonlighting activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design, synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations.
- Pieroni, Marco,Annunziato, Giannamaria,Beato, Claudia,Wouters, Randy,Benoni, Roberto,Campanini, Barbara,Pertinhez, Thelma A.,Bettati, Stefano,Mozzarelli, Andrea,Costantino, Gabriele
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p. 2567 - 2578
(2016/04/10)
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- Further insights into the SAR of α-substituted cyclopropylamine derivatives as inhibitors of histone demethylase KDM1A
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Epigenetics alterations including histone methylation and acetylation, and DNA methylation, are thought to play important roles in the onset and progression of cancer in numerous tumour cell lines. Lysinespecific demethylase 1 (LSD1 or KDM1A) is highly ex
- Pieroni, Marco,Annunziato, Giannamaria,Azzali, Elisa,Dessanti, Paola,Mercurio, Ciro,Meroni, Giuseppe,Trifiró, Paolo,Vianello, Paola,Villa, Manuela,Beato, Claudia,Varasi, Mario,Costantino, Gabriele
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p. 377 - 386
(2015/03/05)
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- Dialkylation of diethyl ethoxycarbonylmethylphosphonate under microwave and solventless conditions
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To further broaden the methods for the heterogeneous phase alkylation of CH acidic compounds, the dialkylation of diethyl ethoxycarbonylmethylphosphonate was studied in the presence of Cs2CO3 under microwave and solvent-free conditio
- Gruen, Alajos,Blastik, Zsofia,Drahos, Laszlo,Keglevich, Gyoergy
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p. 107 - 113
(2014/04/03)
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- Rhodium(III)-catalyzed olefinic C-H alkynylation of acrylamides using tosyl-imide as directing group
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The Rh(III)-catalyzed C-H alkynylation of acrylamide derivative is realized using a hypervalent alkynyl iodine reagent. The use of a weakly coordinating directing group proved to be of critical importance. This reaction displays broad functional group tolerance and high efficiency, which opens a new synthetic pathway to access functionalized 1,3-enyne skeletons.
- Feng, Chao,Feng, Daming,Luo, Yang,Loh, Teck-Peng
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supporting information
p. 5956 - 5959
(2015/01/08)
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- Microwave-assisted alkylation of diethyl ethoxycarbonylmethylphosphonate under solventless conditions
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The reaction of diethyl ethoxycarbonylmethylphosphonate with a series of alkyl halides, under microwave (MW) and solventless conditions at 120°C, in the presence of Cs2CO3 and in the absence of a phase transfer catalyst afforded the corresponding monoalkylated products in yields of >70%. The thermal variant carried out in boiling acetonitrile was slow and led to incomplete conversions. In the MW method, the phase transfer catalyst is substituted by MW irradiation and there is no need for a solvent.
- Gruen, Alajos,Blastik, Zsofia,Drahos, Laszlo,Keglevich, Gyoergy
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experimental part
p. 241 - 246
(2012/07/28)
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- Oxidative coupling reactions of 1,3-diarylpropene derivatives to dibenzo[a,c]cycloheptenes by PIFA
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The oxidative cyclization reactions of a variety of α- benzylcinnamates can be selectively performed with hypervalent iodine as an oxidant. The dibenzo[a,c]cycloheptenes were isolated in up to 55 % yield. When an oxo substrate is applied, the yield was significantly increased. With this synthetic approach, a central intermediate for the synthesis of metasequirin-B was obtained in three steps from very simple starting materials. For this transformation, both aryl moieties have to be activated.
- Hackeloeer, Kristina,Schnakenburg, Gregor,Waldvogel, Siegfried R.
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supporting information; experimental part
p. 6314 - 6319
(2011/12/01)
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- Synthesis and γ-secretase activity of APP substrate-based hydroxyethylene dipeptide isosteres
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Two new APP substrate-based hydroxyethylene isosteres (AT and VI) were prepared and their dipeptide conjugates shown not to inhibit the γ-secretase-mediated formation of either Aβ1-40 or Aβ1-42. The FG isostere and a des-hydroxy hydroxyethylene isostere a
- Nadin, Alan,Owens, Andrew P.,Castro, José L.,Harrison, Timothy,Shearman, Mark S.
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- A useful synthesis of diethyl 1-substituted vinylphosphonates
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A variety of diethyl 1-substituted vinylphosphonates 8 has been conveniently synthesized by piperidine catalyzed decarboxylative condensation of 2-diethoxyphosphorylalkanoic acids and 2-diethoxyphosphorylalkenoic acids 7 with formaldehyde.
- Krawczyk,Koszuk,Bodalski
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p. 1123 - 1128
(2007/10/03)
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- Phosphinic derivatives as new dual enkephalin-degrading enzyme inhibitors: Synthesis, biological properties, and antinociceptive activities
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The development of dual inhibitors of the two zinc metallopeptidases, neprilysin (neutral endopeptidase) and aminopeptidase N involved in the inactivation of the opioid peptides, enkephalins, represents an attractive physiological approach in the search f
- Chen, Huixiong,Noble, Florence,Mothé, Aurélie,Meudal, Hervé,Coric, Pascale,Danascimento, Sophie,Roques, Bernard P.,George, Pascal,Fournié-Zaluski, Marie-Claude
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p. 1398 - 1408
(2007/10/03)
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- Oxidation potential as a measure of the reactivity of anionic nucleophiles. Behaviour of different classes of nucleophiles
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Anodic peak potentials for 42 anionic nucleophiles are reported along with the rate constants for the reactions of the anions with benzyl chloride.By comparing these rate constants with those of the reactions of outer-sphere electron-transfer reagents (radical anions), it has been demonstrated that the reactions of the anions with benzyl chloride are typical single-step SN2 reactions as opposed to a two-step process comprising dissociative single electron transfer (SET) to benzyl chloride followed by radical combination.The data suggest that very electron-rich nucleophilic anions with potentials of -1.5 to -2.2 V (and more negative) with respect to the ferrocenium/ferrocene couple might participate in a SET reaction.The 42 anions studied included representatives of four classes of nucleophiles, viz. sulfur-, carbon-, oxygen- and nitrogen-centred anions.The previously observed correlation of rate constants and anodic peak potential was again found for these anions with the most reactive species having the most negative peak potentials.Correlations by class indicate that the sensitivity of rate constants to changes in peak potential is greatest (and equivalent) for the sulfur-, carbon- and oxygen-anions and for representatives with the same peak potential, the rate constants by class follow the order sulfur > carbon > oxygen.The nitrogen nucleophiles show a significantly lower sensitivity of rate constant to changes in peak potential than do the other three classes.
- Niyazymbetov, Murat E.,Rongfeng, Zhou,Evans, Dennis H.
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p. 1957 - 1962
(2007/10/03)
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- Exploration of Neutral Endopeptidase Active Site by a Series of New Thiol-Containing Inhibitors
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With the aim of characterizing the active site of the neutral endopeptidase and especially its putative S1 subsite, two series of new thiol inhibitors designed to interact with the S1, S'1, and S'2 subsites of the enzyme have been synthesized.These molecules correspond to the general formula HSCH(R1)CH(R2)CONHCH(R3)COOH (series I) and HSCH(R1)CH(R2)CONHCH(R3)CONHCH(R4)COOH (series II).Due to the synthetic pathway used, these inhibitors were obtained as mixtures of four stereoisomers.HPLC separation of the stereoisomers of 17 HSCHCH(CH2Ph)CONHCH(CH3)COOH allowed the stereochemical dependence of the inhibitory potency to be determined.The most active isomer 17b (IC50 = 3.6 nM) is assumed to have the S,S,S stereochemistry as deduced from both NMR and HPLC data.Although none of the inhibitors obtained were significantly more active than thiorphan, HSCH2CH(CH2Ph)CONHCH2COOH (IC50 = 4 nM), which interacts only with the S'1 and S'2 subsites of NEP, their enhanced hydrophobicity is expected to improve their pharmacokinetic properties.All these compounds displayed low affinities for ACE (IC50S > 1 μM).The determination of the IC50S of two inhibitors of series II for NEP and for a mutated enzyme in which Arg102 was replaced by Glu102 allowed their mode of binding to the active site of NEP to be characterized.The R2 and R3 chains fit the S'1-S'2 subsites, while the R4 group is probably located outside the active site.Taken together these results indicate that the R1 chain of these inhibitors creates no additional stabilizing interactions with the active site of NEP.Two hypotheses may account for this: there is no hydrophophobic S1 subsite in NEP or the inhibitors have structures which are too constrained for optimized interactions with the active site.
- Gomez-Monterrey, Isabel,Turcaud, Serge,Lucas, Evelyne,Bruetschy, Luce,Roques, Bernard P.,Fournie-Zaluski, Marie-Claude
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- N-ACYLAMINO ACID DERIVATIVES AND THEIR PHARMACEUTICAL COMPOSITIONS
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An N-acylamino acid derivative of the formula: STR1 wherein the substituents are herein defined or a salt thereof, which is useful as hypotensive drugs.
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- 'CARBA' peptide bond surrogates: Synthesis of Boc-L-Leu-Ψ(CH2-CH2)-L-Phe-OH and Boc-L-Leu-Ψ(CH2-CH2)-D-Phe-OH through a Horner-Emmons reaction
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A synthesis of Boc-L-Leu-Ψ(CH2-CH2)-L-Phe-OH and Boc-L-Leu-Ψ(CH2-CH2)-D-Phe-OH from Boc-βhomo-L-leucinal, through a Horner-Emmons reaction with ethyl 2-(diethylphosphono)-3-phenylpropionate is described. Interme
- Rodriguez,Heitz,Martinez
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p. 7319 - 7322
(2007/10/02)
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- Heterogeneous mediated Alkylation of Ethyl Diethylphosphonoacetate. A "One Pot" Access to α-Alkylated Acrylic Esters
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Ethyl diethylphosphonoacetates are α-alkylated in high yield in a heterogeneous reaction with solid potassium carbonate as base.A "one pot" synthesis of α-alkylated acrylic esters is achiewed in a PO-actived olefination reaction aqueous media, when aqueous potassium carbonate and formaldehyde are added directly to the above reaction mixture.
- Kirschleger, Bernard,Queignec, Rene
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p. 926 - 928
(2007/10/02)
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