- C70Fullerene Catalyzed Photoinduced Aerobic Oxidation of Benzylamines to Imines and Aldehydes
-
C70 fullerene catalyzed photoinduced oxidation of benzylic amines at ambient conditions has been explored here. The developed strategy's main feature includes the additive/oxidant-free conversion of benzylic amine to corresponding imine and aldehydes. The reaction manifests broad substrate scope with excellent function group leniency and is applicable up to the gram scale. Further, symmetrical secondary amines can also be synthesized from benzylic amine in a one-pot two-step process. Various experiments and density functional theory studies revealed that the current reaction involves the generation of reactive oxygen species, single electron transfer reaction, and benzyl radical formation as key steps under photocatalytic conditions.
- Kumar, Inder,Kumar, Rakesh,Gupta, Shiv Shankar,Sharma, Upendra
-
supporting information
p. 6449 - 6457
(2021/05/29)
-
- Activator free, expeditious and eco-friendly chlorination of activated arenes by N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)
-
N-Chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI) has been explored for the first time as a chlorinating reagent for direct chlorination of various activated arenes and heterocycles without any activator. A comparative in-silico study was performed to determine the electrophilic character for NCBSI and commercially available N-chloro reagents to reveal the reactivity on a theoretical viewpoint. The reagent was prepared by an improved method avoiding the use of hazardous t-butyl hypochlorite. This reagent was proved to be very reactive compared to other N-chloro reagents. The precursor of the reagent N-(phenylsulfonyl)benzene sulfonamide was recovered from aqueous spent, which can be recycled to synthesize NCBSI. The eco-friendly protocol was equally applicable for the synthesis of industrially important chloroxylenol as an antibacterial agent.
- Misal, Balu,Palav, Amey,Ganwir, Prerna,Chaturbhuj, Ganesh
-
supporting information
(2021/01/04)
-
- Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells
-
Cancer cells reprogram their metabolism to support growth and to mitigate cellular stressors. The serine synthesis pathway has been identified as a metabolic pathway frequently altered in cancers and there has been considerable interest in developing pharmacological agents to target this pathway. Here, we report a series of indole amides that inhibit human 3-phosphoglycerate dehydrogenase (PHGDH), the enzyme that catalyzes the first committed step of the serine synthesis pathway. Using X-ray crystallography, we show that the indole amides bind the NAD+ pocket of PHGDH. Through structure-based optimization we were able to develop compounds with low nanomolar affinities for PHGDH in an enzymatic IC50 assay. In cellular assays, the most potent compounds inhibited de novo serine synthesis with low micromolar to sub-micromolar activities and these compounds successfully abrogated the proliferation of cancer cells in serine free media. The indole amide series reported here represent an important improvement over previously published PHGDH inhibitors as they are markedly more potent and their mechanism of action is better defined.
- Mullarky, Edouard,Xu, Jiayi,Robin, Anita D.,Huggins, David J.,Jennings, Andy,Noguchi, Naoyoshi,Olland, Andrea,Lakshminarasimhan, Damodharan,Miller, Michael,Tomita, Daisuke,Michino, Mayako,Su, Taojunfeng,Zhang, Guoan,Stamford, Andrew W.,Meinke, Peter T.,Kargman, Stacia,Cantley, Lewis C.
-
supporting information
p. 2503 - 2510
(2019/07/23)
-
- Amino-TEMPO Grafted on Magnetic Multi-Walled Nanotubes: An Efficient and Recyclable Heterogeneous Oxidation Catalyst
-
An efficient and easy recyclable heterogeneous oxidation catalyst was prepared by grafting TEMPO–NH2 moieties on the surface of magnetic multi-walled carbon nanotubes (MWCNT), first by a radical reaction introducing butyric acid moieties on carbon nanotube surface. Subsequently, carboxylic acid moieties were submitted for amidation using TEMPO–NH2. The functionalized nanotubes [MWCNT-{(CH2)3-CO-NH-TEMPO}n] were investigated as a (pre-)catalyst for the oxidation of primary and secondary alcohols for the production of aldehydes and ketones in a Montanari-type catalytic oxidation using the cheap and readily available 1,3-dichloro-5,5-dimethylhydantoin as the terminal oxidant.
- Gambarotti, Cristian,Bj?rsvik, Hans-René
-
p. 1405 - 1412
(2019/01/04)
-
- Amplification of Trichloroisocyanuric Acid (TCCA) Reactivity for Chlorination of Arenes and Heteroarenes via Catalytic Organic Dye Activation
-
Heteroarenes and arenes that contain electron-withdrawing groups are chlorinated in good to excellent yields (scalable to gram scale) using trichloroisocyanuric acid (TCCA) and catalytic Brilliant Green (BG). Visible-light activation of BG serves to amplify the electrophilic nature of TCCA, providing a mild alternative approach to acid-promoted chlorination of deactivated (hetero)aromatic substrates. The utility of the TCCA/BG system is demonstrated through comparison to other chlorinating reagents and by the chlorination of pharmaceuticals including caffeine, lidocaine, and phenazone.
- Rogers, David A.,Bensalah, Adam T.,Espinosa, Alvaro Tomas,Hoerr, John L.,Refai, Fares H.,Pitzel, Amy K.,Alvarado, Juan J.,Lamar, Angus A.
-
supporting information
p. 4229 - 4233
(2019/06/17)
-
- Visible-light photocatalytic activation of N-chlorosuccinimide by organic dyes for the chlorination of arenes and heteroarenes
-
A variety of arenes and heteroarenes are chlorinated in moderate to excellent yields using N-chlorosuccinimide (NCS) under visible-light activated conditions. A screening of known organic dye photocatalysts resulted in the identification of methylene green as the most efficient catalyst to use with NCS. According to mechanistic studies described within, the reaction is speculated to proceed via a single electron oxidation of NCS utilizing methylene green under visible-light photoredox pathway. The photo-oxidation of NCS amplifies the electrophilicity of the chlorine atom of the NCS, thus leading to enhanced reactivity as a chlorinating reagent with aromatic substrates.
- Rogers, David A.,Gallegos, Jillian M.,Hopkins, Megan D.,Lignieres, Austin A.,Pitzel, Amy K.,Lamar, Angus A.
-
-
- In Situ Formed IIII-Based Reagent for the Electrophilic ortho-Chlorination of Phenols and Phenol Ethers: The Use of PIFA-AlCl3 System
-
A new and in situ formed reagent generated by mixing PIFA {bis[(trifluoroacetoxy)iodobenzene]} and AlCl3 was introduced in the organic synthesis for the direct and highly regioselective ortho-chlorination of phenols and phenol ethers. An efficient electrophilic chlorination for these electron-rich arenes as well as the scope of the reaction are described herein. An easy, practical, and open-flask reaction allowed us to introduce a chlorine atom, which is a highly important functional group in organic synthesis. The reproducibility of our method has been demonstrated on gram-scale by carrying out the reaction in 6-bromo-2-naphthol. This halogenation reaction also proceeds in excellent conditions by first preparing the iodine(III)-based chlorinating reagent. Our new chlorinating reagent can be stored at least for two weeks at 4 °C without losing its reactivity.
- Nahide, Pradip D.,Ramadoss, Velayudham,Juárez-Ornelas, Kevin A.,Satkar, Yuvraj,Ortiz-Alvarado, Rafel,Cervera-Villanueva, Juan M. J.,Alonso-Castro, ángel J.,Zapata-Morales, Juan R.,Ramírez-Morales, Marco A.,Ruiz-Padilla, Alan J.,Deveze-álvarez, Martha A.,Solorio-Alvarado, César R.
-
p. 485 - 493
(2018/02/09)
-
- Iron(III)-Catalyzed Chlorination of Activated Arenes
-
A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.
- Mostafa, Mohamed A. B.,Bowley, Rosalind M.,Racys, Daugirdas T.,Henry, Martyn C.,Sutherland, Andrew
-
p. 7529 - 7537
(2017/07/26)
-
- Aggregation-induced emission enhancement in halochalcones
-
A family of push-pull fluorophores, consisting of a chalcone core decorated with electron-donating substituents and halogen atoms, was designed and synthesized. Luminescence studies were performed in solution, aggregate form and in the solid state. Although some compounds are only weakly fluorescent in solution, all are emissive in the solid state showing aggregation-induced emission enhancement. In the crystalline state, the halogen atoms are not involved in halogen bonds but their presence strongly influences the aggregation-induced emission properties of the fluorophores.
- Vaz, Patricia A. A. M.,Rocha, Jo?o,Silva, Artur M.S.,Guieu, Samuel
-
supporting information
p. 8198 - 8201
(2016/10/11)
-
- Aromatic stacking interactions govern catalysis in aryl-alcohol oxidase
-
Aryl-alcohol oxidase (AAO, EC 1.1.3.7) generates H2O2 for lignin degradation at the expense of benzylic and other π system-containing primary alcohols, which are oxidized to the corresponding aldehydes. Ligand diffusion studies on Pleurotus eryngii AAO showed a T-shaped stacking interaction between the Tyr92 side chain and the alcohol substrate at the catalytically competent position for concerted hydride and proton transfers. Bi-substrate kinetics analysis revealed that reactions with 3-chloro- or 3-fluorobenzyl alcohols (halogen substituents) proceed via a ping-pong mechanism. However, mono- and dimethoxylated substituents (in 4-methoxybenzyl and 3,4-dimethoxybenzyl alcohols) altered the mechanism and a ternary complex was formed. Electron-withdrawing substituents resulted in lower quantum mechanics stacking energies between aldehyde and the tyrosine side chain, contributing to product release, in agreement with the ping-pong mechanism observed in 3-chloro- and 3-fluorobenzyl alcohol kinetics analysis. In contrast, the higher stacking energies when electron donor substituents are present result in reaction of O2 with the flavin through a ternary complex, in agreement with the kinetics of methoxylated alcohols. The contribution of Tyr92 to the AAO reaction mechanism was investigated by calculation of stacking interaction energies and site-directed mutagenesis. Replacement of Tyr92 by phenylalanine does not alter the AAO kinetic constants (on 4-methoxybenzyl alcohol), most probably because the stacking interaction is still possible. However, introduction of a tryptophan residue at this position strongly reduced the affinity for the substrate (i.e. the pre-steady state Kd and steady-state Km increase by 150-fold and 75-fold, respectively), and therefore the steady-state catalytic efficiency, suggesting that proper stacking is impossible with this bulky residue. The above results confirm the role of Tyr92 in substrate binding, thus governing the kinetic mechanism in AAO.
- Ferreira, Patricia,Hernández-Ortega, Aitor,Lucas, Fátima,Carro, Juan,Herguedas, Beatriz,Borrelli, Kenneth W.,Guallar, Victor,Martínez, Angel T.,Medina, Milagros
-
p. 3091 - 3106
(2015/08/24)
-
- Oxidation of benzaldehydes to benzoate esters using household bleach and sodium iodide in alcohol solvents
-
Various substituted benzaldehydes were converted into benzoate esters with household bleach and sodium iodide in an alcohol solvent. The reaction works best with methanol. Only 4-chlorobenzaldehyde, 3-nitrobenzaldehyde, and 4-nitrobenzaldehyde reacted completely with 1-propanol under these conditions. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.] Copyright
- Hathaway, Bruce A.,Dekastle, Christopher A. D.,Arnett, Brianna A.
-
p. 660 - 664
(2014/01/17)
-
- Reductive carbonylation of aryl halides employing a two-chamber reactor: A protocol for the synthesis of aryl aldehydes including 13C- and D-isotope labeling
-
A protocol has been developed for conducting the palladium-catalyzed reductive carbonylation of aryl iodides and bromides using 9-methylfluorene-9- carbonyl chloride (COgen) as a source of externally delivered carbon monoxide in a sealed two-chamber system (COware), and potassium formate as the in situ hydride source. The method is tolerant to a wide number of functional groups positioned on the aromatic ring, and it can be exploited for the isotope labeling of the aldehyde group. Hence, reductive carbonylations run with 13COgen provide a facile access to 13C-labeled aromatic aldehydes, whereas with DCO2K, the aldehyde is specifically labeled with deuterium. Two examples of double isotopic labeling are also demonstrated. Finally, the method was applied to the specific carbon-13 labeling of the β-amyloid binding compound, florbetaben.
- Korsager, Signe,Taaning, Rolf H.,Lindhardt, Anders T.,Skrydstrup, Troels
-
p. 6112 - 6120
(2013/07/26)
-
- Copper-catalyzed domino route to natural nostoclides and analogues: A total synthesis of nostoclides i and II
-
An original and convenient domino route to natural nostoclides I and II has been developed using a two-step sequence consisting of a copper-cat-alyzed tandem reaction associated with Suzuki cross-coupling. The methodology employed for this total synthesis appeared to be an interesting and suffi-ciently flexible tool to allow the synthesis of numer-ous analogues of these nostoclides.
- Ngi, Samuel Inack,Petrignet, Julien,Duwald, Romain,El Hilali, El Mostafa,Abarbri, Mohamed,Duchêne, Alain,Thibonnet, Jér?me
-
supporting information
p. 2936 - 2941
(2014/03/21)
-
- NOVEL STILBENE ANALOGS
-
The present invention relates to Stilbene derivatives of the general formula I or a pharmaceutically acceptable salt thereof have properties such as high water solubility, bioavailability and effective as carcinostatics.
- -
-
Page/Page column 10
(2010/05/13)
-
- Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase
-
Fungal AAO (aryl-alcohol oxidase) provides H2O2 for lignin biodegradation. AAO is active on benzyl alcohols that are oxidized to aldehydes. However, during oxidation of some alcohols, AAO forms more than a stoichiometric number of H2O2 molecules with respect to the amount of aldehyde detected due to a double reaction that involves aryl-aldehyde oxidase activity. The latter reactionwas investigated using different benzylic aldehydes, whose oxidation to acids was demonstrated by GC-MS. The steady- and presteady state kinetic constants, together with the chromatographic results, revealed that the presence of substrate electron-withdrawing or electron-donating substituents had a strong influence on activity; the highest activity was with p-nitrobenzaldehyde and halogenated aldehydes and the lowest with methoxylated aldehydes. Moreover, activity was correlated to the aldehyde hydration rates estimated by 1H-NMR. These findings, together with the absence in the AAO active site of a residue able to drive oxidation via an aldehyde thiohemiacetal, suggested that oxidation mainly proceeds via the gem-diol species. The reaction mechanism (with a solvent isotope effect, 2H2O kred, of approx. 1.5)would be analogous to that described for alcohols, the reductive half-reaction involving concerted hydride transfer from the a-carbon and proton abstraction from one of the gem-diol hydroxy groups by a base. The existence of two steps of opposite polar requirements (hydration and hydride transfer) explains some aspects of aldehyde oxidation by AAO. Site-directed mutagenesis identified two histidine residues strongly involved in gem-diol oxidation and, unexpectedly, suggested that an active-site tyrosine residue could facilitate the oxidation of some aldehydes that show no detectable hydration. Double alcohol and aldehyde oxidase activities of AAO would contribute to H2O2 supply by the enzyme. The Authors Journal compilation
- Ferreira, Patricia,Hernandez-Ortega, Aitor,Herguedas, Beatriz,Rencoret, Jorge,Gutierrez, Ana,Martinez, Maria Jesus,Jimenez-Barbero, Jesus,Medina, Milagros,Martinez, Angel T.
-
body text
p. 585 - 593
(2011/02/24)
-
- 1, 2 DISUBSTITUTED HETEROCYCLIC COMPOUNDS
-
1,2-disubstituted heterocyclic compounds which are inhibitors of phosphodiesterase 10 are described. Also described are processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of mammals, including human(s) for central nervous system (CNS) disorders and other disorders which may affect CNS function. Among the disorders which may be treated are neurological, neurodegenerative and psychiatric disorders including, but not limited to, those associated with cognitive deficits or schizophrenic symptoms.
- -
-
Page/Page column 113-114
(2010/01/30)
-
- The β-silicon effect. II. Substituent effects on the solvolysis of 1-aryl-2-(aryldimethylsilyl)ethyl 3,5-dinitrobenzoates
-
Solvolysis rates of 2-(dimethylphenylsilyl)-1-(Y-phenyl)ethyl 3,5-dinitrobenzoates were determined conductimetrically in 60% (v/v) aqueous ethanol. In order to clarify the nature of the β-Si participation quantitatively, the effects of α-aryl substituents on the rates were analyzed by means of the Yukawa-Tsuno Eq. The α-aryl (Y)-substituent effect at 25°C was correlated with r ? 1:0 and ρ = -3:0, which is significantly reduced compared with that of -5:45 for the non-silylated 1-arylethyl system. There is a linear relationship between log k Y=kH of silylated and non-silylated substrates: log(k Y/kH)Si = 0:52 log(kY=k H)non-Si. This is the same form as the extended Bronsted relationship. The Bronsted coefficient α = 0:52 appeared to be consistent with the neighboring silyl-participation in the silyl-bridged transition state.
- Fujio, Mizue,Umezaki, Yuzo,Alam, Md. Ashadul,Kikukawa, Kiyoshi,Fujiyama, Ryoji,Tsuno, Yuho
-
p. 1091 - 1099
(2007/10/03)
-
- Novel imidazole derivatives with anti-inflammatory activity
-
Novel imidazole derivatives of formula I and their salts, solvates and prodrugs, wherein the meanings of the different radicals are as shown in the description. Said compounds are useful as anti-inflammatory agents.
- -
-
-
- Imidazopyridinone derivatives and their use as phosphodiesterase inhibitors
-
A compound (Ia): wherein the variables are defined in the specification, its prodrug or a pharmaceutically acceptable salt thereof useful in the treatment of angina, hypertension etc.
- -
-
-
- Compositions containing aromatic aldehydes and their use in treatments
-
Disclosed are pharmaceutical and cosmetic compositions containing aromatic aldehyde compounds. Some of the disclosed compositions are useful as topical therapeutics for treating inflammatory dermatologic conditions. Some of the compositions are useful in transdermal and other systemic dose forms for treating other inflammatory conditions in mammals.
- -
-
-
- Synthesis of (1R,2S)-1-(3′-chloro-4′-methoxyphenyl)-1,2- propanediol (trametol) and (1R,2S)-1-(3′,5′-dichloro-4′- methoxyphenyl)-1,2-propanediol, chlorinated fungal metabolites in the natural environment
-
(1R,2S)-1-(3′-Chloro-4′-methoxyphenyl)-1,2-propanediol (Trametol, 3), a metabolite of the fungus Trametes sp. IVP-F640 and Bjerkandera sp. BOS55, was synthesized by employing Sharpless asymmetric dihydroxylation as the key step. Similarly, the (1R,2S)-isomer of 1-(3′,5′-dichloro- 4′-methoxyphenyl)-1,2-propanediol (4), another metabolite of Bjerkandera sp. BOS55, was synthesized by asymmetric dihydroxylation.
- Kousaka, Takeshi,Mori, Kenji
-
p. 697 - 701
(2007/10/03)
-
- Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease
-
Carbamate derivatives of N-propargylaminoindans (Series I) and N-propargylphenethylamines (Series II) were synthesized via multistep procedures from the corresponding hydroxy precursors. The respective rasagiline- and selegiline-related series were designed to combine inhibitory activities of both acetylcholine esterase (AChE) and monoamine oxidase (MAO) by virtue of their carbamoyl and propargylamine pharmacophores. Each compound was tested for these activities in vitro in order to find molecules with similar potencies against each enzyme. Compounds with such dual AChE and MAO inhibitory activities are expected to have potential for the treatment of Alzheimer's disease. The observed SAR also offers insight into the requirements of the active sites on these enzymes. A carbamate moiety was found to be essential for AChE inhibition, which was absent in the corresponding hydroxy precursors. The propargyl group caused 2-70-fold decrease in AChE inhibitory activity (depending on the position of the carbamoyl group) of Series I, but had little or no effect in Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were either equipotent to, or slightly (2- to 5-fold) less active as AChE inhibitors than, the corresponding compounds in Series II, while the 4-carbamyloxyphenyls were more potent. The presence of the carbamate moiety in 6- and 7-carbamyloxyphenyls of Series I, considerably decreased MAO-A and -B inhibitory activity, compared to that of the parent hydroxy analogues, while the opposite was true for Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were 2-3 orders of magnitude weaker MAO inhibitors while the 4- carbamyloxyphenyls were equipotent with the corresponding compounds in Series II. In both series, N-methylation of the propargylamine enhanced the MAO (A and B equally) inhibitory activities and decreased the AChE inhibitory activity. Two candidates belonging to the indan and tetralin ring systems (24c, 27b) and one phenethylamine (53d) were identified as possible leads for further development based on the following criteria: (a) comparable AChE and MAO-B inhibitory activities, (b) good to moderate AChE inhibitory activity, and (c) lack of strong MAO-A selectivity. However, it is likely that these compounds will be metabolized to the corresponding phenols, with inhibitory activities against AChE and/or MAO-A or -B, different from those of the parent carbamates. Thus, the apparent enzyme inhibition will be a result of the combined inhibition of all of these individual metabolites. The results of our ongoing in vivo screening programs will be published elsewhere.
- Sterling, Jeffrey,Herzig, Yaacov,Goren, Tamar,Finkelstein, Nina,Lerner, David,Goldenberg, Willy,Miskolczi, Istvan,Molnar, Sandor,Rantal, Ferenc,Tamas, Tivadar,Toth, Gyorgy,Zagyva, Adela,Zekany, Andras,Lavian, Gila,Gross, Aviva,Friedman, Rachel,Razin, Michal,Huang, Wei,Krais, Boris,Chorev, Michael,Youdim, Moussa B.,Weinstock, Marta
-
p. 5260 - 5279
(2007/10/03)
-
- Calcium receptor-active molecules
-
The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca2+and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.
- -
-
-
- Chlorometabolite production by the ecologically important white rot fungus Bjerkandera adusta
-
Two strains of the basidiomycete, Bjerkandera adusta (DAOM 215869 and BOS55) produce in static liquid culture, phenyl, veratryl, anisyl and chloroanisyl metabolites (CAM's) (alcohols, acids and aldehydes) as well as a series of compounds not previously known to be produced by Bjerkandera species: 1-phenyl, 1-anisyl, 1-(3-chloro-4-methoxy) and 1-(3,5-dichloro-4-methoxy) propan-1,2-diols, predominantly as erythro diastereomers with 1R, 2S absolute configurations. 1-Anisyl-propan-1,2-diol and 1-(3,5-dichloro-4-methoxy)-propan-1,2-diol are new metabolites for which the names Bjerkanderol A and B, respectively, are proposed. Experiments with static liquid cultures supplied with 13C66- and 13C9-L-phenylalanine showed that all identified aromatic compounds (with the exception of phenol) can be derived from L-phenylalanine. For the aryl propane diols, the 13C label appeared only in the phenyl ring and the benzylic carbon, suggesting a stereoselective re-synthesis from a C7 and a C2-unit, likely aromatic aldehyde and decarboxylated pyruvate, respectively. Other compounds newly discovered to be derived from phenylalanine by this white rot fungus include phenylacetaldehyde and phenylpyruvic, phenylacetic, phenyllactic, mandelic and phenyl glyoxylic (benzoyl formic) acids. For both strains, cultures supplied with Na37Cl showed incorporation of 37Cl in all identified chlorometabolites. Veratryl alcohol and the CAM alcohols, which occur in both strains and can be derived from L-phenylalanine (all 13C-labelled), have reported important physiological functions in this white rot fungus. Possible mechanisms for their formation through the newly discovered compounds are discussed.
- Silk,Aubry,Lonergan,Macaulay
-
p. 1603 - 1616
(2007/10/03)
-
- Calcium receptor-active molecules
-
The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca2+ and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.
- -
-
-
- 4-Benzylamino-1-chloro-6-substituted phthalazines: Synthesis and inhibitory activity toward phosphodiesterase 5
-
We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the 6- position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F(2α) (10-5 M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.
- Watanabe, Nobuhisa,Kabasawa, Yasuhiro,Takase, Yasutaka,Matsukura, Masayuki,Miyazaki, Kazuki,Ishihara, Hiroki,Kodama, Kohtarou,Adachi, Hideyuki
-
p. 3367 - 3372
(2007/10/03)
-
- Calcium receptor-active molecules
-
The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca2+ and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.
- -
-
-
- Mild chlorination of aromatic compounds with tin(IV) chloride and lead tetraacetate
-
SnCl4/Pb(OAc)4 acts as a safe source of Cl2 for the chlorination of aromatic compounds. A variety of aromatic compounds are effectively chlorinated with SnCl4/Pb(OAc)4 under mild conditions. The mixture is a selective chlorinating agent, particularly with polyalkylbenzenes, polycyclic aromatic compounds and anisoles.
- Muathen, Hussni A.
-
p. 8863 - 8866
(2007/10/03)
-
- Evaluation of isomeric 4-(chlorohydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines as dopamine D-1 antagonists
-
The isomeric 4-(3-chloro-4-hydroxyphenyl)- and 4-(4-chloro-3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines, the N-methyl derivative of the 4-(4-chloro-3-hydroxyphenyl)isomer, and 4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline were synthesized and evaluated for dopamine D-1 antagonist activity. The 4-(3-chloro-4-hydroxyphenyl) and the 4-(3-hydroxyphenyl) isomer possessed similar potencies as D-1 antagonists. Introduction of the N-methyl group enhanced potency about twofold. The 'pharmacophore' for selective dopamine D-1 antagonist activity appears to be a tertiary 2-(3-hydroxyphenyl)-2-phenethylamine.
- Riggs,Nichols,Foreman,Truex
-
p. 1887 - 1891
(2007/10/02)
-