Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury

A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.

Optical 2-benzyl-5-hydroxy-4-oxopentanoic acids against carboxypeptidase A:Synthesis,kinetic evaluation and X-ray crystallographic study

2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group in 1 binding to CPA,2-benzyl-5- benzyloxy-4-oxopentanoic acid 2 was also synthesized and evaluated.The inhibition constants show that both L-1 and D-1 were shown to have strong binding affinity with L-1 being more potent than its enantiomer by 165-fold.On the other hand,the inhibition constant ...

Novel Method for Selective Debenzylation Under Maintenance of Fluoro Atom Substituted on β-Amino Acids

tert-Butyl （R）-3-amino-3-（3-fluorophenyl）propanoate（5） was prepared with conventional debenzylation method. However, the tert-butyl （R）-3-[（S）-1-phenylethyl-amino]-3-（3-fluorophenyl） propanoate（6） and tert-butyl （R）-3-amino-3-phenylpropanoate（7） were generated as the byproducts under the general catalytic hydrogenation Pd（OH）2/C-H2 conditions. So a series of experiments was performed to optimize the reaction conditions so that product 5 could be obtained with high purity and yield. Finally an effective catalytic system, Pd/C-HCOOH-CH3OH, was discovered.

Role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor regulation in stress-induced pain chronification

Persistent postsurgical pain is a serious issue in public health, which has received increased interest in recent years. Previous studies have reported that psychological factors promote the development of chronic postsurgical pain. However, it is unclear how chronification of postsurgical pain occurs. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor(AMPA) phosphorylation in the central nervous system plays a critical role in synaptic plasticity and contributes to central sensitization and chronic pain development. Here, we discuss the role of AMPA receptor regulation in stress-induced pain chronification after surgery.

Synthetic Approach for Novel Fluorine Substituted <i>α</i>-Aminophosphonic Acids Containing 1,2,4-Triazin-5-One Moiety as Antioxidant Agents

Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin- 5-one (6a-f) have been obtained from fluoroacylation of 6-(2&prime;-amino-5&prime;-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (1) followed by ammonilysis to give the corresponding 3-amino-derivative 3. Condensation of compound 3 with nitro/halogenated aromatic aldehydes yielded the Schiff bases 4. The simple addition of diethyl phosphonate to compound 4 produced the α-amino phosphonates 5. Acidic hydrolysis of compound 5 produced the fluorine substituted α-amino acids derivatives 6. Structures of the new compounds have been established with the help of elemental analysis and spectral measurements. Also, the products evaluated as antioxidants, where the fluorinated α-amino phosphonic acids 6 are more active than the other synthesized systems.

Thermodynamic solvation of a series of homologous α-amino acids in non-aqueous mixture of ethylene-glycol and N,N-dimethyl formamide

Standard free energies (ΔG0t(i) ) and entropies (ΔS0t(i)) of transfer of some homologous α-amino acids viz. glycine (gly), dl-alanine (ala), dl-α-amino butyric acid (aba) and dl-nor-valine (nor-val) from protic ethylene glycol (EG) to dipolar aprotic N,N-dimethyl formamide (DMF) have been evaluated from solubility measure-ments at five equidistant temperatures i.e from 15 to 350C. The observed ΔG0t(i) and TΔS0t(i) Vs composition profiles are complicated because of the various interaction effects. The chemical effects of the transfer Gibbs energies (ΔG0t.ch(i)) and entropies of transfer (ΔS0t.ch(i)) have been obtained after elimination of cavity effect, estimated by the scaled particle theory and dipole-dipole interaction effects, estimated by the use of Keesom-orientation expression. The chemical contributions of transfer energetics of homologous α-amino acids are guided by the composite effects of increased dispersion interaction, basicity and decreased acidity, hydrogen bonding effects and solvophobic solvation of ethylene glycol and N, N-dimethyl formamide mixed solvent as compared to that of reference solvent (ethylene glycol).

Chemical Interaction UO2Cl2 with α-and β-Amino Acids in Aqueous and Organic Solution

This paper presents the results of the search of biologically active uranium compounds such as amino acids. We first received and examined X-ray and IR （infrared radiation） spectroscopy of uranium complexes with α- and β-amino acids in aqueous and organic solution. We proposed a method for direct synthesis of complex organic compounds of uranium chloride UO2Cl2 with α- andβ-amino acids for the synthesis of drugs for the treatment of cancer.

Flotation behavior and adsorption mechanism of(1-hydroxy-2-methyl-2-octenyl) phosphonic acid to cassiterite

The flotation behavior and adsorption mechanism of novel（1-hydroxy-2-methyl-2-octenyl） phosphonic acid（HEPA） to cassiterite were investigated by micro-flotation tests, zeta potential measurements, FTIR determination and density functional theory（DFT） calculation. The flotation results demonstrated that HEPA exhibited superior collecting performance compared with styrene phosphonic acid（SPA）. The cassiterite recovery maintained above 90% over a wide pH range of 2-9 with 50 mg/L HEPA. The results of zeta potential measurement and FTIR detection indicated that the adsorption of HEPA onto cassiterite was mainly attributed to the chemisorption between HEPA monoanions and Sn species on mineral surfaces. The DFT calculation results demonstrated that HEPA monoanions owned higher HOMO energy and exhibited a better affinity to cassiterite than SPA, which provided very clear evidence for the stronger collecting power of HEPA presented in floatation test and zeta potential measurement.

Effects of β-Amino Butyric Acid Induced Rice Blast Resistance on Reactive Oxygen Metabolism

[Objective] This study was to understand the effects of β-Amino butyric acid(abbreviated as BABA) induced rice blast resistance on reactive oxygen metabolism. [Method] Using the cultivar Chaochan 2 that is highly susceptible to disease as experimental material, the changes of catalase(CAT), and superoxide dismutase(SOD) and MDA activities in rice treated by BABA were investigated. [Result] In rice plants treated by BABA, the activities of CAT and SOD increased, meanwhile the MDA content also rose to some extent, resulting in the disease resistance to rice blast. [Conclusion] By influencing reactive oxygen metabolism, BABA endows rice plants with resistance to rice blast. BABA is safe to environment and has highly resistance-inducing capacity, it could be generalized in production.

Different characteristics of 40 kinds of free amino acids and 5-amino levulinic acid between wines and sakes(Japanese rice wines)

Based on a systemic analysis for the globa1 burden of disease study from 1990 to 2016,the Global Burden of Diseases(GBD)2016 Alcohol Collaborators reported that alcohol use was a 1eading nisk factor for globa1 disease burden and caused substantial health loss.However,alcoholic dnink(wines and sakes)contains abundant nutrients,particularly fermentable amino acids denived from grapes and rice.Amino acid nutrition and metabolism is strongly associated with health and preventiom against various diseases.The purpose of this study was to elucidate 40 kinds of free amino acid(FAA)profles in wines and sakes.In addition,the present study also provided the contents of 5-aminolevulinic acid(5-AI A)involved in the vital functionality of mitochondria.FAAs were detected and analyzed by use of an automatic amino acid analyzer.Aromatic amino acid,branched chain amino acid and Fischer ratio were calculated for each beverage.Individua1 FAAs showed significant differences between wines and sakes.Sakes abundantly contained almost all FAAs whereas wines had just a lttle content in some FAAs.Sakse were rich in arginine,glycine,alanine,valine,glutamic acid and leucine,while wines were remarkably nich in proline(Pro).Wines showed increased FAA levels in 6 kinds of variables(4-hydroxyproline,3-methy1 histidine,B-alanine,a-aminobutyric acid,Pro and a.-aminoadipic acid).In functionally characteristic FAAs,both wines and sakes were considerably abundant in y aminobutynic acid and 5-AI A The total amount of aromatic amino acid and branched chain amino acid were markedly higher in sakes than in wines.These results revealed that there were the apparent different characteristics in FAA profiles between wines and sakes.This difference resulted from fermentation process in wines(single fermentation)and sakes(paralle1 double fermentation).Forty kinds of FAA profiles are more usefu1 in investigating characteristics of the taste of wines and sakes.In future,detailed FAA analysis has the potential to find functional nutrients such as 5-AI A,whereas other foods generally contain ittle amount of these FAAs.

Content and Partial Characterization of Unknown N in Humic Acids

INTRODUCTION Nitrogen is a key component of soil organic matter. Only when we have succeeded in characterizing the major part of organic N-containing compounds will we be able to understand fully the transformation reactions in the soil and to use soil-N more efficiently. However, only about 1/ 4——1/ 2 of the total N in humic acid (HA), one of the major constituents of soil organic matter, can be accounted for as amino acids and amino sugars, and most of the remainder has still to be accounted for. It has been

Syntheses and Structural Characterization of Dimethyltin Complexs of N-(3-Methoxysalicylidene)-α-amino Acid

Three new dimethyltin complexes of N-（3-methoxysalicylidene）-α-amino acid,（CH3）2Sn（3-CH3O-2-OC6H3CH=NCHRCOO）（R = H,1;CH3,2;（CH3）2CH,3）,have been synthe-sized by treating dimethyltin dichloride with the potassium salt of the ligand and characterized by elemental analysis,IR and 1H NMR spectra.The crystal structure of [（CH3）2Sn（3-CH3O-2-OC6H3CH=NCH2COO）（CH3OH）]2 H2O（1a）,formed from methanol solution of 1,has been deter-mined.The crystal belongs to the monoclinic system,space group C/2c with a = 20.636（3）,b = 7.8854（9）,c = 20.668（2） ,β= 113.265（2）°,V = 3089.7（6） 3,Z = 4,Dc = 1.707 g/cm3,= 1.675 mm-1,F（000） = 1592,R = 0.0301 and wR = 0.0841.In complex 1a,the tin atom is six-coordinate and possesses a distorted [SnC2NO3] octahedral geometry with the two methyl groups occupying the trans positions.The weak Sn O interactions and intermolecular hydrogen bonds connected the molecules into an infinite chain.

A practical synthesis of trifluorophenyl R-amino acid:The key precursor for the new anti-diabetic drug sitagliptin

Sitagliptin is the first new anti-diabetic drug in DPP-Ⅳ inhibitor class. The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment. Though the specific β-amino acid can be easily made from the corresponding R-amino acid by Arndt-Eistert hornologation, the optically pure precursor R-amino acid is difficult to prepare. We herein reported a practical protocol to make the trifluorophenyl substituted R-amino acid 4 in 〉99.9% ee and 40.3% yield by the enzymatic resolution employing enantioselective hydrolysis and a general separation procedure. This protocol requires only cheap starting materials and friendly reaction condition. The procedure not only allows people to prepare the drug substance, but also provides an alternative method for prepareing the rare α-amino acid and the subsequent β-amino acid.

Synthesis,Crystal Structure,and Magnetic Property of One 3D Nickel Coordination Polymer Based on 2-Hydroxy-5-(3',5'-terephthalic acid)Pyridine and 1,4-Bis(1-imdazoly)benzene

One novel nickel coordination polymer, {[Ni（OTP）（bib）1.5（H2O）]·2H2O}n（1, H2 OTP = 2-hydroxy-5-（3＇,5＇-terephthalic acid） pyridine, bib = 1,4-bis（1-imdazoly）benzene）, has been synthesized and characterized by elemental analysis（EA）, IR, powder X-ray diffraction（PXRD）, and thermogravimetric（TG） analyses. The crystal of 1 crystallizes in monoclinic, space group P21/n with a = 12.2860（5）, b = 13.8246（6）, c = 19.0140（8） A, β = 104.3870（1）°, V = 3128.2（2） A3, Z = 4, C32H28N7 Ni O8, Mr = 697.32, Dc = 1.481 g/cm^3, F（000） = 1444 and μ（Mo Kα） = 0.684 mm-1. The final R = 0.0704 and w R = 0.1764 for 5485 observed reflections with I 2σ（I） and R = 0.1087 and wR = 0.2010 for all data. Topology analysis reveals that complex 1 is a 3D 2-fold interpenetrated {4^4·6^6}-nov net based on the 1D [Ni（OTP）]n chain and the 2D [Ni2（bib）3]n sql sheet. And the variable-temperature magnetic susceptibility measurements exhibit weak antiferromagnetic coupling interaction.

The design and synthesis of a novel organophosphorus compound containing the structure of both β-amino acid and β-aminophosphonate

A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.

Synthesis and Structural Characterization of Some Diorganotin Complexes of N-(3,5-Dibromosalicylidene)-α-amino Acid and their Diphenyltin Dichloride Adducts

The title complexes, R′2Sn(3,5-Br2-2-OC6H2CH=NCHRCOO), and their diphenyltindichloride adduct, R′2Sn(3,5-Br2-2-OC6H2CH=NCHRCOO)?SnPh2Cl2, were synthesized and char-acterized by elemental analysis, IR, H and C NMR and X-ray single crystal diffraction. The 1 13structural features of the compounds were described.

Facile and Efficient Syntheses of (±)-2,6-Dimethyl-6-hydroxy-2,7-octadienoic Acid and Its Methyl Ester

The facile and efficient total syntheses of monoterpenoid acid 7a and its ester 7b, isolated from Artemisia siebert and Piper aduncum respectively, can be completed in four steps with an overall yield 41%.

A convenient synthesis of methyl 2-hydroxy-4-oxo-4-(substituted phenyl) butanoates from malic acid

A synthesis of methyl 2-hydroxy-4-oxo-4-（substituted phenyl）butanoates has been accomplished using Friedel-Crafts acylation of substituted benzenes with 2-acetoxybutanoyl chloride. The key feature of this strategy is that various 4-arylbutanoates can be obtained conveniently, which are important intermediates for the synthesis of biologically active compounds including ACE inhibitors.？2009 Yong Sup Lee. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Dietary <i>γ</i>-Aminobutyric Acid Shortens the Life Span of Stroke-Prone Spontaneously Hypertensive Rats

Dietary γ-amino butyric acid (GABA) has been suggested to decrease systolic blood pressure. This study aimed to ex-amine the effects of dietary GABA on the life span of stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, life span was determined for SHRSPs provided 1% NaCl solution or 0.01% GABA in 1% NaCl solution as drinking water. The life span of the GABA-fed group (76.3 ± 1.65 days) was significantly shorter than that of the control group (81.6 ± 0.88 days). The results of this study may not be applicable to humans. Future studies will be necessary to elucidate the mechanism underlying this phenomenon.

A Theoretical Study of <i>β</i>-Amino Acid Conformational Energies and Solvent Effect

The conformations of four β-amino acids in a model peptide environment were investigated using Hartree-Fock (HF) and density functional theory (DFT) methods in gas phase and with solvation. Initial structures were obtained by varying dihedral angles in increments of 45° in the range 0° - 360°. Stable geometries were optimized at both levels of theory with the correlation consistent double-zeta basis set with polarization functions (cc-pVDZ). The results suggest that solvation generally stabilizes the conformations relative to the gas phase and that intramolecular hydrogen bonding may play an important role in the stability of the conformations. The β3 structures, in which the R-group of the amino acid is located on the carbon atom next to the N-terminus, are somewhat more stable relative to each other than the β2 structures which have the R-group on the carbon next to the carbonyl.