A versatile synthetic route to chiral quinoxaline derivatives from amino acids precursors

Summary The synthesis ofN-protected L-amino acid (3-benzylquinoxalin-2-yl) hydrazide derivatives is reported here. 3-Benzyl-2-hydrazinoquinoxaline was prepared and then coupled withN-Boc-L-amino acids including; Alanine, Valine, Leucine, Phenylalanine, Tyrosine, Serine and Proline in the presence of HBTU as a coupling reagent to provide the expected product with high yield and purity. The products were deprotected by p-toluenesulphonic acid in acetonitrile and then the tosylate salts were evaluated for antibacterial and antifungal activity. Abbreviations: HBTU, N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide Boc,t-butyloxycarbonyl, DIEA, diisopropylethylamine; DMF, N,N-dimethylformamide; PTSA, p-toluenesulphonic acid, TEA, triethyl amine. Amino acids are abbreviated and designated following the rules of the IUPAC-IUB Commission of BiochemicalNomenclature (J. Biol. Chem., 247 (1972) 977).     

Alternative synthetic route to chiral N-substituted camphor-derived beta-amino alcohols

An alternative route from (1R)-(+)-camphor to chiral N-substituted camphor-derived beta-amino alcohol (4b-e) consists of four steps with a total yield of 28%. N-Alkylation of camphor-derived beta-amino alcohol (4a) involves condensation and hydride reduction in one pot without isolation of intermediates. Condensation of 4a with aldehydes or ketones generates a mixture of 1,3-oxazolidines (6) and imino-alcohols (7), which are reduced to 4b-e by NaBH(4).     

Allylation and propargylation of chiral cyanopropanoates: an efficient route to long chain alpha-substituted alpha-methyl alpha-amino acids

alpha-Methyllysine and 2-amino-2-methylundecanoic acid, two alpha,alpha-disubstituted unnatural glycines, were synthesized using highly diastereoselective allylation or propargylation of chiral (1S,2R,4R)-10-dicyclohexylsulfamoylisobornyl 2-cyanopropanoate as the key step to introduce the long side chain. Chirality 16:106-111, 2004.     

A versatile enrichment of functionalized calixarene as a facile sensor for amino acids

Amino acids are the most important part of the human biological system due to their role in living processes. The role of amino acids stretches beyond their traditional role as a building block for proteins, and deficiency of amino acids could lead to decreased immunity, digestive problems, depression, fertility issues, lower mental alertness, slowed growth in children, and many other health issues. The acute detection of amino acids is necessary to determine the human health domain. Here, in this review, we summarize and study the calixarenes as complexes that are of immeasurable value and their utilization for amino acid detection. Key factors such as noncovalent forces, limit of detection, and the supramolecular chemistry of calixarenes with amino acids have been well described. This study presents the most recent efforts made towards the development of potential and highly efficient calixarene-based sensors for the detection of amino acids.     

Free amino acids from pollens

Pollens from Pinus canariensis, P. nigra, P. pinaster, P. pinea, Castanea sativa, Magnolia grandiflora, Olea sativa cv frantoio, cv itrana, cv pisciottana were examined for their free amino acid composition. A large amount of proline was found in all species; pollens of Olea also contain a large amount of serine.     

Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives

Summary A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L-Glu in producing IPs.     

Application of cross-linked beta-cyclodextrin polymer for adsorption of aromatic amino acids

Beta-cyclodextrin (beta-CyD) was cross-linked by hexamethylene diisocyanate and the polymer was investigated for adsorption of aromatic amino acids (AAA) from phosphate buffer. High adsorption rates were observed at the beginning and the adsorption equilibrium was then gradually achieved in about 45 min. The adsorption of AAA decreased with the increase of initial concentration and also temperature. Under the same conditions, the adsorption efficiencies of AAA were in the order of L-tryptophan (L-Trp) > L-phenylalanine (L-Phe) > L-tyrosine (L-Tyr). Much higher adsorption values, up to 52.4 and 43.0 mg/g for L-Trp and L-Phe, respectively, at 50 mmol/L and 3.2 mg/g for L-Tyr at 2 mmol/L, were obtained with the beta-CyD polymer at 37 degrees C. It was shown that the adsorption of AAA on the beta-CyD polymer was consistent with the Freundlich isotherm equation. The adsorption of mixed aromatic amino acids and branched-chain amino acids (BCAA) showed that AAA were preferentially adsorbed with adsorption efficiencies 10-24%, while those of BCAA were lower than 2%. It seems that the structure and hydrophobicity of amino acid molecules are responsible for the difference in adsorption, by influencing the strength of interactions between amino acid molecule and the polymer.     

Drugs for chiral discrimination: Non-coded amino acids and dipeptides by asymmetric hydrogenation

The enantiomers of Propranolol, Pindolol, and Carazolol, well-known β-blockers, have been used to prepare cationic aminophosphine phosphinite rhodium complexes. Propraphos-Rh and Pindophos-Rh are very efficient catalysts in the asymmetric hydrogenation of N-Boc-protected unusual dehydroamino acid derivatives. Carazolol-Rh is less suitable in both activity and enantioselectivity. Under the same conditions, N-Boc-protected dehydrodipeptides are hydrogenated with diastereoselectivities between 70 and 90% de. Chirality 10:535–539, 1998. © 1998 Wiley-Liss, Inc.     

猪血粉分离氨基酸的研究

本文报道了从猪血粉中提取分离七种氨基酸(L—Phe、L—Tyr、L—His·HCl、L—lys·HAC、L—Arg·HCl、L—leu、L—Val)的小试工艺。通过合成一系列专用树脂(AAS—1、AAS—2、D083)对现行工艺脱酸、脱色及层析分离等过程作了较大改进,使猪血粉分离氨基酸的生产工艺全部树脂化,并使氨基酸收率大幅度提高。经周期性实验,每批投料130g猪血粉,七种氨基酸总回收率平均达34.9%。(占血粉量)。经自检产品质量基本符合注射用结晶氨基酸原料标准。     

Electrochromatographic enantioseparation of amino acids using polybutylmethacrylate-based chiral monolithic column by capillary electrochromatography

This article describes the development of a polybutylmethacrylate‐based monolithic capillary column as a chiral stationary phase. The chiral monolithic column was prepared by polymerization of butyl methacrylate (BMA), ethylene dimethacrylate (EDMA), and N‐methacryloyl‐l ‐glutamic acid (MAGA) in the presence of porogens. The porogen mixture included N,N‐dimethyl formamide and phosphate buffer. MAGA was used as a chiral selector. The effect of MAGA content was investigated on electrochromatographic enantioseparation of d,l ‐histidine, d,l ‐tyrosine, d,l ‐phenyl alanine, and d,l ‐glutamic acid. The effect of acetonitrile (ACN) content in mobile phase on electro‐osmotic flow was also investigated. It was demonstrated that the poly(BMA‐EDMA‐MAGA) monolithic chiral column can be used for the electrochromatographic enantioseparation of amino acids by capillary electrochromatography (CEC). The mobile phase was ACN/10 mM phosphate buffer (45:55%) adjusted to pH 2.7. It was observed that l ‐enantiomers of the amino acids migrated before d ‐enantiomers. The separation mechanism of electrochromatographic enantioseparation of amino acids in CEC is discussed. Chirality 24:606–609, 2012. © 2012 Wiley Periodicals, Inc.     

Unusual amino acids VIII. Asymmetric hydrogenation of some heteroaryl-N-CBZ and N-BOC aminocinnamic acid derivatives

Summary (Z)--[(Benzyloxy)- or (tert.-butyloxy)carbonylamino]- (thienyl)-or (furyl)-acrylic acids and their esters were prepared by known methods and hydrogenated to the corresponding optically active alanine derivatives with optical yields in the range of 58–93% ee using the cationic rhodium complex of PROPRAPHOS.     

An electrochemical sensor based on cellulose nanocrystal for the enantioselective discrimination of chiral amino acids

A novel electrochemical sensor based on 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanocrystals (TOCNCs) and l-cystines (l-Cys) modified Au electrode (TOCNC/l-Cys/Au) has been fabricated for detection and discrimination of the enantiomers of phenylalanine (Phe), leucine (Leu), and valine (Val). The three amino acids are in connection with metabolism diseases. The TOCNC/l-Cys/Au electrode exhibited obvious peak current difference for the amino acid enantiomers by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The TOCNCs on the electrode surface expressed different interactions with d- and l-amino acids, so the electrochemical recognitions of the three amino acid enantiomers were achieved. TOCNCs were characterized by Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM). The modified electrodes were characterized by SEM and electrochemical techniques. According to DPV, peak currents of the two enantiomers decreased linearly with their concentrations. Furthermore, satisfactory results were obtained when this electrode was applied to measure the d- and l-Phe mixture. The experimental results show that TOCNCs are suitable material for chiral sensor. The contrast of serum sample of healthy people and patients with type 2 diabetes also was proposed, and significant difference was exhibited on the modified electrode. This work is significant for the screening, diagnosis, and treatment of multiple metabolic diseases.     

Ⅱ型抗癌晶体蛋白抗肝癌作用的关键芳香族氨基酸

为探讨Ⅱ型抗癌晶体蛋白(Parasporin-2)上与抗肝癌作用相关的关键氨基酸,利用5-BU对Parasporin-2活性区编码DNA(P2Y)进行PCR诱变,之后在大肠杆菌中表达,产物纯化后经MTT法检测其对肝癌细胞系和正常肝细胞系的作用。获得的9个突变体其抗肝癌活性差异极大,其中P2M1和P2M8对两种肝癌细胞系SMMC7721和Bel7402均有较强的细胞毒杀作用而不影响正常肝细胞系Chang-liver。比较了P2M1、P2M8和P2Y的二级结构与三级结构,发现二级结构上的变化如β折叠变长或α螺旋增加影响着Ⅱ型抗癌晶体蛋白的抗肝癌活性。基于突变体间氨基酸序列比对、突变体与受体间分子对接以及模拟突变等研究的结果表明,位点52、56、58和208上的氨基酸残基特别是芳香族氨基酸在Parasporin-2与受体间的互作中可能起着重要作用。     

3-Ketoglutarate generation in pancreatic B-cell mitochondria regulates insulin secretory action of amino acids and 2-keto acids

The various neutral amino acids and aliphatic 2-keto acids exhibit differential effects on insulin secretion. The common denominator for all these effects is the 2-ketoglutarate generation in the pancreatic B-cell mitochondria. The neutral amino acidsl-leucine andl-norvaline and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, 2-ketovalerate, and 2-keto-3-methylvalerate all stimulate insulin secretion and increase 2-ketoglutarate generation in pancreatic B-cell mitochondria through activation of glutamate dehydrogenase and transamination withl-glutamate andl-glutamine, respectively. The neutral amino acidsl-valine,l-norleucine, andl-alanine and the aliphatic 2-keto acids 2-ketoisovalerate and pyruvate do not stimulate insulin secretion and do not increase 2-ketoglutarate generation in pancreatic B-cell mitochondria. Inhibition of 2-keto acid induced insulin secretion byl-valine andl-isoleucine is accompanied by reduced 2-ketoglutarate generation in pancreatic B-cell mitochondria. Thus intramitochondrial 2-ketoglutarate generation in pancreatic B-cells may regulate the insulin secretory potency of amino acids and 2-keto acids.     

Chiral separation of underivatized amino acids in supercritical fluid chromatography with chiral crown ether derived column

The supercritical fluid chromatographic separation of underivatized amino acids was explored using immobilized chiral crown ether column CROWNPAK CR-I (+) and mass spectrometric detection. The type of modifier, acidic additives, and the role of water were investigated. Enantioseparation was achieved for all 18 amino acids investigated with short retention times (less than 3 minutes) and average resolution of greater than 5.0. Analysis of enantiomerically pure standards demonstrated the D enantiomer eluted first for all amino acids using a CROWNPAK CR-I (+) column.     

Gustatory sensitivity of the herbivore Tilapia zillii to amino acids

The gustatory sensitivity of the herbivorous fish Tilapia zillii was investigated using electrophysiological techniques. Integrated responses from facial taste nerves were recorded during stimulation by l l amino acids. All compounds proved to be effective stimuli. The relative stimulatory efficacy (RSE) determined at 1 × 10 ⁻³ m indicated that stimuli can be organized into three groups on the basis of similarity of efficacy. Effects of pH which altered the RSE of some amino acids are documented. Amino acid RSE differed to some extent from those of previously studied carnivorous fish. There was concordance between the composition of preferred food, effective feeding stimuli and the peripheral receptor responses. These observations support the hypothesis that peripheral chemosensitivity might serve as a mechanism of feeding specialization in some fish.     

A significant pool of amino acids is adsorbed on blood cell membranes

It is well known that the amino acids in the blood are distributed between the plasma and inside the cells. This study was conducted to determine whether amino acids can be located adsorbed on blood cell membranes. The amino acid concentration in the deproteinized haemolysed blood was higher than that in the fraction of blood after removal of the blood cell membranes by centrifugation. These results showed that a pool of amino acids representing 21.1% of the whole blood cell amino acids was adsorbed on the blood cell membranes of adult Wistar rats. The non-polar amino acids showed high adsorption on the membrane, whereas out of the polar amino acid group, only the non-ionic amino acids did adsorb.Bioquimica i Biologia Molecular. Dept. de Biologia Fonamental i Ciencies de la Salut.     

l-threo- and l-erythro-2-amino-3-hydroxyhex-4-ynoic acids: New amino acids from Tricholomopsis rutilans

2-Amino-3-hydroxyhex-4-ynoic acid, reported previously from Tricholomopsis rutilans, was shown to be a mixture of its threo- and erythro-forms. They were separated from each other and characterized by elementary analysis, optical rotation, TLC, IR, NMR spectra, catalytic hydrogenation, and by chemical synthesis. Their configurations were determined by the comparison of their hydrogenation products with known threo- and erythro-2-amino-3-hydroxyhexanoic acids.     

Unusual amino acids VI. Substituted arylamino acids by asymmetric hydrogenation of N-Cbz and N-Boc protected dehydroamino acid derivatives

Substituted N-Cbz and N-Boc protected arylamino acrylic acids and esters have been prepared and used in asymmetric hydrogenations catalyzed by PROPRAPHOSRh. Stereoselectivities > 90% ee could be achieved, the rate of which is dependent on the position of the substituent in the aromatic ring. The N-Boc derivatives provide advantages compared with the N-Cbz analogues. The amino acid derivatives were fully characterized by ¹⁹F, ¹³C, and ¹H NMR spectroscopy. © 1996 Wiley-Liss, Inc.