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Corresponding N (corresponding + n)
Selected AbstractsSynthesis of Substituted Oxazoles from N -Acyl-,-hydroxyamino Acid DerivativesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 27 2008Paula M. T. Ferreira Abstract Several N -acyl-,-hydroxyamino acids were prepared and treated with di- tert -butyl dicarbonate in the presence of 4-(dimethylamino)pyridine, followed by treatment with N,N,N,,N, -tetramethylguanidine to give the corresponding N -acyldehydroamino acids in good to high yields. These were then treated with I2/K2CO3 followed by 1,8-diazabicyclo[5.4.0]undec-7-ene. The methyl esters of N -acyldehydroaminobutyric acid gave the corresponding substituted oxazoles in good to high yields. The N -acyldehydrophenylalanines gave 5-phenyloxazole derivatives in low to moderate yields together with ,-iododehydrophenylalanines. Under the same conditions, N -acyldehydroalanines failed to give the corresponding oxazoles. However, when the reaction was carried out in the absence of DBU, it was possible to isolate the ,,,-diiododehydroalanine derivatives. Although the reason for the different reactivities of the N -acyldehydroamino acids is not completely clear to us, cyclic voltammetry studies showed that the less-reactive derivatives have higher reduction potentials. This suggests that the double bonds in dehydroaminobutyric acid derivatives are more susceptible to electrophilic attack by iodine.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] The Ritter Reaction under Truly Catalytic Brønsted Acid ConditionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2007Roberto Sanz Abstract Simple organic acids like 2,4-dinitrobenzenesulfonic acid (DNBSA) catalyze the Ritter reaction of secondary benzylic alcohols giving rise to the corresponding N -benzylacetamides in usually high yields. Reactions can be conducted without exclusion of oxygen and without the need of dry solvents. With tertiary ,,,-dimethylbenzylic alcohols a different pathway involving a formal dimerization reaction takes place under the acid-catalytic conditions used. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Nucleophilic Vinylic Substitution (SNV) of Activated Alkoxymethylene Derivatives with 6-Aminoquinoxaline,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2005Jozef Salo Abstract Treatment of 6-aminoquinoxaline with ,,,-diactivated alkoxymethylene derivatives gave the corresponding N -(quinoxalin-6-yl)enamines. A variant of the SNV reaction mechanism was proposed for substitution of the alkoxymethylene compounds, on the basis of the structures of the precursor enol ether and the vinylic substitution product and on computations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Synthesis of (R)-(,)-2-Fluoronorapomorphine , A Precursor for the Synthesis of (R)-(,)-2-Fluoro- N -[11C]propylnorapomorphine for Evaluation as a Dopamine D2 Agonist Ligand for PET InvestigationsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2005Kåre Søndergaard Abstract 2-Fluoronorapomorphine, the PET labelling precursor to 2-fluoro- N -[11C]propylnorapomorphine, was prepared in 13 steps from codeine in a total yield of 10,%. Codeine was converted in four steps into N -benzylnorcodeine which was oxidised by using the Swern protocol. Subsequent acid-catalysed rearrangement afforded N -benzylnormorphothebaine which was selectively triflylated at the 2-position and pivaloylated at the 11-position. The triflate underwent palladium-catalysed amination with benzophenone imine. Amination conditions required sequential base addition to give substantial conversion of the triflate to the corresponding N -substituted benzophenone imine. After acidic hydrolysis the resulting aniline was transformed into the 2-fluoro compound via the Balz,Schiemann reaction. Hydrogenolysis of the N -benzyl group followed by deprotection of the catechol moiety using BBr3 provided 2-fluoronorapomorphine. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Val-Ala Dipeptide Isosteres by Hydrocyanation of ,,-Amino ,,,-Unsaturated Ketones , Control of Stereoselectivity by the N -Protecting GroupEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2003Fabio Benedetti Abstract Three diastereoisomeric hydroxyethylene isosters of the Val-Ala dipeptide were synthesized from ,,,-unsaturated ketones 1 derived from N -Boc- and N,N -dibenzyl- L -valine. The enones were hydrocyanated with diethylaluminum cyanide to give the corresponding ,-cyano ketones with the stereoselectivity depending on the protecting group. N -Boc protected enone 1a gave a 1:1 mixture of anti and syn adducts 4a, 5a while the corresponding N,N -dibenzyl compound 1c gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride reduction of the resulting cyano ketones is also controlled by the protecting group, resulting in opposite stereoselectivities for N -Boc and N,N -dibenzyl compounds. The cyano alcohols thus obtained were converted, in several steps, into two series of enantiomerically pure hydroxyethylene isosters of the Val-Ala dipeptide. In the first series the hydroxy group and the N -terminal of the isoster are internally protected through the formation of an oxazolidine; in the second series the hydroxy group and the C-terminal are protected as lactone. Two oxazolidines (28, 29), corresponding to syn,syn and syn,anti 4-hydroxy-5-amino acid isosters, and three lactones (23,25), corresponding to syn,syn, syn,anti, and anti,anti isosters were obtained by this approach. (© Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2003) [source] Effective Methods for the Synthesis of N -Methyl , -Amino Acids from All Twenty Common , -Amino Acids Using 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-onesHELVETICA CHIMICA ACTA, Issue 11 2006Andrew Abstract N -Methyl , -amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N -methyl , -amino acids. Starting from , -amino acids, two approaches were used to prepare the corresponding N -methyl , -amino acids. First, , -amino acids were converted to N -methyl , -amino acids by the so-called ,1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt,Eistert procedure to afford N -protected N -methyl , -amino acids derived from the 20 common , -amino acids. These compounds were prepared in yields of 23,57% (relative to N -methyl , -amino acid). In a second approach, twelve N -protected , -amino acids could be directly homologated by the Arndt,Eistert procedure, and the resulting , -amino acids were converted to the 1,3-oxazinan-6-ones in 30,45% yield. Finally, reductive cleavage afforded the desired N -methyl , -amino acids in 41,63% yield. One sterically congested , -amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N -methyl , -amino acid 61 in 71% yield (Scheme,2). Thus, our protocols allow the ready preparation of all N -methyl , -amino acids derived from the 20 proteinogenic , -amino acids. [source] Synthesis, CD Spectra, and Enzymatic Stability of ,2 -Oligoazapeptides Prepared from (S)-2-Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and LeuHELVETICA CHIMICA ACTA, Issue 12 2003Gérald Lelais , -Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs.,1 and 2). We report here the synthesis and spectroscopic investigations of ,2 -peptide analogs consisting of (S)-3-aza- , -amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N -benzyl- L - , -amino acids with an oxaziridine (Scheme,1). Couplings and fragment coupling of the 3-benzylaza- ,2 -amino acids and a corresponding tripeptide (N -Boc/C -OMe strategy) with common peptide-coupling reagents in solution led to ,2 -di, ,2 -tri-, and ,2 -hexaazapeptide derivatives, which could be N -debenzylated (4,9; Schemes,2,4). The new compounds were identified by optical rotation, and IR, 1H- and 13C-NMR, and CD spectroscopy (Figs.,4 and 5) and high-resolution mass spectrometry, and, in one case, by X-ray crystallography (Fig.,3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the ,2 -azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N -Boc and C -OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)- 314 -helical structure. The N -Boc- ,2 -tri and N -Boc- ,2 -hexaazapeptide esters, 7 and 9, were shown to be stable for 48,h against the following peptidases: pronase, proteinase,K, chymotrypsin, trypsin, carboxypeptidase,A, and 20S proteasome. [source] Oxidation of Primary Amines to N -Monoalkylhydroxylamines using Sodium Tungstate and Hydrogen Peroxide-Urea ComplexADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2005Akbar Heydari Abstract The sodium tungstate-catalyzed (10,mol,%) oxidation of primary amines with a urea-hydrogen peroxide complex (UHP) gives the corresponding N -monoalkylhydroxylamines, which are important biologically active compounds, in good to excellent yields. The method is applicable for a wide range of primary amines, including chiral benzylic amines, ,-1,2-hydroxylamine and ,-amino esters. [source] Electronic structure of iron(II),porphyrin nitroxyl complexes: Molecular mechanism of fungal nitric oxide reductase (P450nor)JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2006Nicolai Lehnert Abstract Density functional calculations are employed to investigate key intermediates of the catalytic cycle of fungal nitric oxide reductase (P450nor). The formal Fe(II),nitroxyl species Fe(II)NO/(,) can principally exist in the two spin-states S = 0 and S = 1. In the S = 0 case, a very covalent FeNO , bond is present, which leads to an electronic structure description that is actually intermediate between Fe(I)NO and Fe(II)NO,. In contrast, the S = 1 case shows a ferrous Fe(II)NO complex with the extra electron being stored in the , system of the porphyrin ligand. Importantly, the Fe(II)NO/(,) species are very basic. The electronic structures and spectroscopic properties of the corresponding N- and O-protonated forms are very different, and unequivocally show that the Mb,HNO adduct (Mb-Myoglobin) prepared by farmer and coworkers is in fact N-protonated. The presence of an axial thiolate ligand enables a second protonation leading to the corresponding Fe(IV)NHOH, species, which is identified with the catalytically active intermediate I of P450nor. This species reacts with a second molecule of NO by initial electron transfer from NO to Fe(IV) followed by addition of NO+ forming an NN bond. This is accompanied by an energetically very favorable intramolecular proton transfer leading to the generation of a quite stable Fe(III)N(OH)(NOH) complex. This way, the enzyme is able to produce dimerized HNO under very controlled conditions and to prevent loss of this ligand from Fe(III). The energetically disfavoured tautomer Fe(III)N(OH2)(NO) is the catalytically productive species that spontaneously cleaves the NOH2 bond forming N2O and H2O in a highly exergonic reaction. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1338,1351, 2006 [source] Synthesis and spectroscopic studies of optically active n -acetyl butenoates and n -acetyl-2-alkyl-pyrrolin-4-onesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2002Efstathios Gavrielatos The synthesis of a series of optically active N -acetyl butenoates 3,5 is described using a facile methodology. These butenoates undergo cyclization to the corresponding N -acetyl-2-alkyl-pyrrolin-4-ones 6,7 retaining their stereochemical integrity. The structure of the newly synthesized compounds has been elucidated through 1H- 13C NMR, IR spectroscopy and their enantiomeric excesses have been measured by chiral HPLC analysis. [source] Radiosynthesis of 2- exo -(2,-[18F]Fluoro-3,-(4-fluorophenyl)-pyridin-5,-yl)-7-azabicyclo[2.2.1]heptane ([18F]F2PhEP), a potent epibatidine-based radioligand for nicotinic acetylcholine receptor PET imagingJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 6 2006Gaëlle Roger Abstract 2- exo -(2,-Fluoro-3,-(4-fluorophenyl)-pyridin-5,-yl)-7-azabicyclo[2.2.1]heptane (F2PhEP), a novel, epibatidine-based, ,4,2-selective nicotinic acetylcholine receptor antagonist of low toxicity, as well as the corresponding N- Boc-protected chloro- and bromo derivatives as precursors for labelling with fluorine-18 were synthesized from 7- tert -butoxycarbonyl-7-azabicyclo[2.2.1]hept-2-ene in 13, 19 and 8% overall yield, respectively. [18F]F2PhEP was prepared in 8,9% overall yield (non-decay-corrected) using 1 mg of the bromo derivative in the following two-step radiochemical process: (1) no-carrier-added nucleophilic heteroaromatic ortho- radiofluorination with the activated K[18F]F-Kryptofix®222 complex in DMSO using microwave activation at 250 W for 90 s, followed by (2) quantitative TFA-induced removal of the N -Boc protective group. Radiochemically pure (>95%) [18F]F2PhEP (1.48,1.66 GBq, 74,148 GBq/µmol) was obtained after semi-preparative HPLC (Symmetry® C18, eluent aqueous 0.05 M NaH2PO4 CH3CN: 78/22 (v:v)) in 75,80 min starting from an 18.5 GBq aliquot of a cyclotron-produced [18F]fluoride production batch. Copyright © 2006 John Wiley & Sons, Ltd. [source] Radiosynthesis and in vivo study of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine: a promising new sigma-1 receptor ligandJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2005Jun Zhao Abstract The novel sigma-1 receptor PET radiotracer [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([18F]WLS1.002, [18F]-2) was synthesized (n=6) by heating the corresponding N -ethylmesylate precursor in an anhydrous acetonitrile solution containing [18F]fluoride, Kryptofix K222 and potassium carbonate for 15 min. Purification was accomplished by reverse-phase HPLC methods, providing [18F]-2 in 59±8% radiochemical yield (EOB), with specific activity of 2.89±0.80 Ci/µmol (EOS) and radiochemical purity of 98.3±2.1%. Rat biodistribution studies revealed relatively high uptake in many organs known to contain sigma-1 receptors, including the lungs, kidney, heart, spleen, and brain. Good clearance from normal tissues was observed over time. Blocking studies (60 min) demonstrated high (>80%) specific binding of [18F]-2 in the brain, with reduction also noted in other organs known to express these sites. Copyright © 2005 John Wiley & Sons, Ltd. [source] NMR characterization of new 10-membered-ring macrolactones and dihydrobenzophenazine-5-one, oxidized derivatives of benzo[a]phenazinesMAGNETIC RESONANCE IN CHEMISTRY, Issue 7 2004Marília O. F. Goulart Abstract Peroxidation of the phenazine of ,-lapachone using m -ClC6H4CO3HCH2Cl2 furnished a macrolactone with a rigid 10-membered ring, and the corresponding N -oxide, along with a dihydrobenzophenazine-5-one. All of the new compounds were fully characterized by spectroscopic methods, with the unambiguous assignment of the hydrogens and carbon NMR signals for the N -oxide, with the aid of 2-D NMR, mainly COSY, HMQC, HSQC and HMBC. For the other two compounds some signals could not be assigned owing to their own intrinsic features. Copyright © 2004 John Wiley & Sons, Ltd. [source] Alternating poly(ester amide)s from succinic anhydride and ,,,-amino alcohols: synthesis and thermal characterization,,POLYMER INTERNATIONAL, Issue 10 2003Thomas Fey Abstract Alternating poly(ester amide)s 6a,e from succinic anhydride and ,,,-amino alcohols H2N,(CH2)x,OH (x = 2,6) 2a,e were obtained in two steps: ,-carboxyl-,-hydroxy amides 3a,e were prepared from the starting materials in a highly selective reaction, followed by a polycondensation reaction. 1H and 13C NMR analyses of the poly(ester amide)s clearly reveal the alternating microstructure. The poly(ester amide)s with homologous ,,,-amino alcohols H2N,(CH2)x,OH (x = 2,6) are semi-crystalline materials, their melting points show the odd/even effect observed for [n]-polyamides and [n]-polyurethanes. Heating the poly(ester amide)s 6a,e yields the corresponding N -(hydroxyalkyl) imides 4a,e with no trace of cyclic ester amides. Theoretical calculations revealed that the cyclic ester amides 5a,e are clearly richer in energy than the isomeric N -(hydroxyalkyl) imides. These results show that cyclic ester amides can not be prepared from N -(hydroxyalkyl) imides by ring-enlargement reactions. Copyright © 2003 Society of Chemical Industry [source] Crystallization and preliminary crystallographic studies of the recombinant dihydropyrimidinase from Sinorhizobium meliloti CECT4114ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 12 2006Sergio Martínez-Rodríguez Dihydropyrimidinases are involved in the reductive pathway of pyrimidine degradation, catalysing the hydrolysis of 5,6-dihydrouracil and 5,6-dihydrothymine to the corresponding N -carbamoyl ,-amino acids. This enzyme has often been referred to as hydantoinase owing to its industrial application in the production of optically pure amino acids starting from racemic mixtures of 5-monosubstituted hydantoins. Recombinant dihydropyrimidinase from Sinorhizobium meliloti CECT4114 (SmelDhp) has been expressed, purified and crystallized. Crystallization was performed using the counter-diffusion method with capillaries of 0.3,mm inner diameter. Crystals of SmelDhp suitable for data collection and structure determination were grown in the presence of agarose at 0.1%(w/v) in order to ensure mass transport controlled by diffusion. X-ray data were collected to a resolution of 1.85,Å. The crystal belongs to the orthorhombic space group C2221, with unit-cell parameters a = 124.89, b = 126.28, c = 196.10,Å and two molecules in the asymmetric unit. A molecular-replacement solution has been determined and refinement is in progress. [source] Probing Enzyme Promiscuity of SGNH HydrolasesCHEMBIOCHEM, Issue 15 2010Dr. Ivana Le Abstract Several hydrolases of the SGNH superfamily, including the lipase SrLip from Streptomyces rimosus (Q93MW7), the acyl-CoA thioesterase I TesA from Pseudomonas aeruginosa (Q9HZY8) and the two lipolytic enzymes EstA (from P. aeruginosa, O33407) and EstP (from Pseudomonas putida, Q88QS0), were examined for promiscuity. These enzymes were tested against four chemically different classes of a total of 34 substrates known to be hydrolysed by esterases, thioesterases, lipases, phospholipases, Tweenases and proteases. Furthermore, they were also analysed with respect to their amino acid sequences and structural homology, and their phylogenetic relationship was determined. The Pseudomonas esterases EstA and EstP each have an N-terminal domain with catalytic activity together with a C-terminal autotransporter domain, and so the hybrid enzymes EstAN,EstPC and EstPN,EstAC were constructed by swapping the corresponding N- and C-terminal domains, and their hydrolytic activities were compared. Interestingly, substrate specificity and kinetic measurements indicated a significant influence of the autotransporter domains on the catalytic activities of these enzymes in solution. TesA, EstA and EstP were shown to function as esterases with different affinities and catalytic efficacies towards p -nitrophenyl butyrate. Of all the enzymes tested, only SrLip revealed lipase, phospholipase, esterase, thioesterase and Tweenase activities. [source] Functional Characterization of the Recombinant N -Methyltransferase Domain from the Multienzyme Enniatin SynthetaseCHEMBIOCHEM, Issue 9 2007Till Hornbogen Dr. Abstract A 51 kDa fusion protein incorporating the N -methyltransferase domain of the multienzyme enniatin synthetase from Fusarium scirpi was expressed in Saccharomyces cerevisiae. The protein was purified and found to bind S -adenosyl methionine (AdoMet) as demonstrated by cross-linking experiments with 14C-methyl-AdoMet under UV irradiation. Cofactor binding at equilibrium conditions was followed by saturation transfer difference (STD) NMR spectroscopy, and the native conformation of the methyltransferase was assigned. STD NMR spectroscopy yielded significant signals for H2 and H8 of the adenine moiety, H1' of D -ribose, and SCH3 group of AdoMet. Methyl group transfer catalyzed by the enzyme was demonstrated by using aminoacyl- N -acetylcysteamine thioesters (aminoacyl-SNACs) of L -Val, L -Ile, and L -Leu, which mimic the natural substrate amino acids of enniatin synthetase presented by the enzyme bound 4,-phosphopantetheine arm. In these experiments the enzyme was incubated in the presence of the corresponding aminoacyl-SNAC and 14C-methyl-AdoMet for various lengths of time, for up to 30 min. N -[14C-Methyl]-aminoacyl-SNAC products were extracted with EtOAc and separated by TLC. Acid hydrolysis of the isolated labeled compounds yielded the corresponding N -[14C-methyl] amino acids. Further proof for the formation of N - 14C-methyl-aminoacyl-SNACs came from MALDI-TOF mass spectrometry which yielded 23,212 Da for N -methyl-valyl-SNAC, accompanied by the expected postsource decay (PSD) pattern. Interestingly, L -Phe, which is not a substrate amino acid of enniatin synthetase, also proved to be a methyl group acceptor. D -Val was not accepted as a substrate; this indicates selectivity for the L isomer. [source] | ||||||||||