- Accelerated tert-butyloxycarbonyl deprotection of amines in microdroplets produced by a pneumatic spray
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Protection and deprotection of organic compounds in multistep reactions using functional groups such as tert-butoxycarbonyl (Boc), is widely performed in synthetic organic chemistry. Reaction rate acceleration studies in spray-based ionization methods (electrosonic spray, paper spray, nanospray) have become increasingly common. Here, we demonstrate reaction rate acceleration of Boc deprotection using easy ambient sonic-spray ionization (EASI), a pneumatic technique which does not involve an applied voltage, in a teaching laboratory setting. The goal of this laboratory exercise was to explore acceleration in a previously unexplored spray-based reaction, while emphasizing in a pedagogic setting the importance of protecting groups for multistep synthesis. Rate acceleration factors of more than an order of magnitude were observed in the uncharged micron-sized droplets generated by EASI. The effect of reaction conditions on reaction acceleration was examined including changes in the type of acid, reagent concentration ratios and syringe pump flow rates. Student knowledge was assessed by pre-laboratory assignments, post-laboratory reports and oral interviews.
- Fedick, Patrick W.,Bain, Ryan M.,Bain, Kinsey,Mehari, Tsdale F.,Cooks, R. Graham
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- Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties
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Ryanodine receptors (RyRs) activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the D-alanine acid and D-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points, 1H NMR, 13C NMR, elemental analysis and specific optical rotation analysis. The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10 mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5 mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80% and 90% respectively at 0.0001 mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.
- Zhou, Shaa,Zhou, Sha,Xie, Yongtao,Meng, Xiangde,Wang, Baolei,Xiong, Lixia,Yang, Na,Li, Zhengming
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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- Instability of Amide Bond Comprising the 2-Aminotropone Moiety: Cleavable under Mild Acidic Conditions
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An unusual hydrolysis/solvolysis of the classical acyclic amide bond, derived from N-troponylaminoethylglycine (Traeg) and α-amino acids, is described under mild acidic conditions. The reactivity of this amide bond is possibly owed to the protonation of the troponyl carbonyl functional group. The results suggest that the Traeg amino acid is a potential candidate for protecting and caging of the amine functional group of bioactive molecules via a cleavable amide bond.
- Balachandra, Chenikkayala,Sharma, Nagendra K.
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- Photochemical desulfurization of L-cysteine derivatives
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Thiol groups can be reductively eliminated at room temperature by a photochemical method which makes use of triethylboron, triethylphosphite and visible light. Thus, after treating L-Cys 1a, D-Pen 1b, L-Cys-OMe 1c and glutathione (γ-L-Glu-L-Cys-Gly) 3, the corresponding desulfurized compounds L-Ala 2a, D-Val 2b, L-Ala-OMe 2c and γ-L-Glu-L-Ala-Gly 4, respectively, are prepared in high yields and with retention of configuration.
- Gonzalez, Asensio,Valencia, Gregorio
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- A New Set of Isoreticular, Homochiral Metal-Organic Frameworks with ucp Topology
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A new isoreticular series of metal-organic frameworks, called UHM-25 (UHM: University of Hamburg Materials), based on the copper paddle wheel motif and a novel set of homochiral linkers has been synthesized. Starting from amino acids available from the chiral pool a synthesis procedure was established that allows a straightforward, multigram scale synthesis of homochiral linkers in 4-5 steps. These linkers carry substituents that have been proven useful in stereoselective organic chemistry, such as the Evans auxiliary or chiral amino alcohols. The resulting MOFs only differ in the chiral moiety provided by the amino acid starting material. The structure of UHM-25 is composed of cuboctahedral cages of Cu2 paddle wheel motifs connected by the isophthalate moieties of the linker. These cages are linked via the bent backbone of the linker resulting in a primitive cubic arrangement, giving rise to the rare underlying (3,4)-c binodal net ucp. MOFs of the UHM-25 series show surface areas up to SBET = 1900 m2/g. Postsynthetic modification reactions with excellent conversion rates confirmed the accessibility to the chiral groups. Furthermore, UHM-25-Pro bearing a prolinol functionality was used in a self-directed, enantioselective aldol addition of acetaldehyde, demonstrating the potential of the UHM-25 series with regard to heterogeneous, stereoselective catalysis.
- Sartor, Michael,Stein, Timo,Hoffmann, Frank,Fr?ba, Michael
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- Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines
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The synthesis of (R) (+) 4 methyl 2 (1 naphthylmethyl)imidazoline hydrochloride (2) and (S) (-) 4 methyl 2 (1 naphthylmethyl)imidazoline hydrochloride (3) is presented. The synthesis involves the preparation of (R) (+) and (S) (-) 1,2 diaminopropane dihydrochloride and then allowing the appropriate diaminopropane to react with ethyl 1 naphthyliminoacetate hydrochloride in the presence of triethylamine. The parent compound, naphazoline, is a potent α adrenoreceptor agonist (-log ED50 = 7.22), whereas the methylated derivatives, 2 and 3, were moderately potent antagonists (pA2 = 5.6 and 5.8, respectively) of the α adrenoreceptor. Compounds 2 and 3 also produced blockade of the response to histamine on the rabbit aorta, but at concentrations approximately 20 times higher than necessary to produce equal blockade of the α adrenoreceptor.
- Miller,Hsu,Ruffolo Jr.,Patil
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- Crystallographic insight-guided nanoarchitectonics and conductivity modulation of an n-type organic semiconductor through peptide conjugation
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Crystallographic insight-guided nanoarchitectonics of peptide-conjugated naphthalene diimide (NDI) is described. In a bio-inspired approach, non-proteinogenic α-amino isobutyric acid (Aib)- and alanine (Ala)-derived peptides orchestrated the 1D achiral and 2D chiral molecular ordering of NDI, respectively, which resulted in modulation of nanoscale morphology, chiroptical and conductivity properties.
- Pandeeswar,Khare, Harshavardhan,Ramakumar, Suryanarayanarao,Govindaraju
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- N-acylated alanine methyl esters (NAMEs) from Roseovarius tolerans, structural analogs of quorum-sensing autoinducers, N-acylhomoserine lactones
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The Roseobacter clade is one of the most important bacteria group living in the ocean. Liquid cultures of Roseovarius tolerans EL 164 were investigated for the production of autoinducers such as N-acylhomoserine lactones (AHLs) and other secondary metabolites. The XAD extracts were analyzed by GC/MS. Two AHLs, Z7-C14: 1-homoserine lactone (HSL) and C15: 1-HSL, were identified. Additionally, the extract contained five compounds with molecular-ion peaks at m/z 104, 145, and 158, thus exhibiting mass spectra similar to those of AHLs with corresponding peaks at m/z 102, 143, and 156. Isolation of the main compound by column chromatography, NMR analysis, dimethyl disulfide derivatization for the determination of the location of the CiC bond and finally synthesis of the compound with the proposed structure confirmed the compound to be (Z)-N-(hexadec-9-enoyl)alanine methyl ester. Four additional minor compounds were identified as C14: 0-, C15: 0-, C16: 0-, and C17: 1-N-acylated alanine methyl esters (NAMEs). All NAMEs have not been described from natural sources before. A BLASTp search showed the presence of AHL-producing luxI genes, but no homologous genes potentially responsible for the structurally closely related NAMEs were found. The involvement of the NAMEs in chemical communication processes of the bacteria is discussed. Copyright
- Bruns, Hilke,Thiel, Verena,Voget, Sonja,Patzelt, Diana,Daniel, Rolf,Wagner-Doebler, Irene,Schulz, Stefan
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- Chiral iminoesters derived from d-glyceraldehyde in [3+2] cycloaddition reactions. Asymmetric synthesis of a key intermediate in the synthesis of neuramidinase inhibitors
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Silver-catalyzed endo-selective and copper-catalyzed exo-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from d-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors.
- Galvez, Jose A.,Diaz-De-Villegas, Maria D.,Alias, Miriam,Badorrey, Ramon
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- Synthesis and photophysics of benzazole based triazoles with amino acid-derived pendant units. Multiparametric optical sensors for BSA and CT-DNA in solution
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Herein we report the synthesis of a series of amino acid-derived triazoles by an organocatalytic cycloaddition reaction between azides and carbonyl compounds, catalyzed by a simple amine. These compounds present absorption maxima located in the UV-B ascribed to fully spin and symmetry allowed electronic transitions and a main fluorescence emission in the UV-A (~380 nm) with a relatively large Stokes shift (5700 cm?1). No significant solvatochromism was observed in both ground and excited states. Unexpectedly, the benzoxazole derivatives presented much higher fluorescence quantum yield values (40–80%) of compared to the sulfur analogues (3–6%). In addition, the DNA binding assays indicated that these compounds presented strong interaction with CT-DNA, which could be attributed to π-stacking and intermolecular hydrogen-bonding. The interaction of the benzazoles with bovine serum albumin (BSA) was also investigated, where a suppression mechanism was observed. In each case, docking was performed to better understand the observed interactions.
- Debia, Natalí P.,Rodríguez, Juan J.P.,da Silveira, Carolina H.,Chaves, Otavio A.,Iglesias, Bernardo A.,Rodembusch, Fabiano S.,Lüdtke, Diogo S.
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- Chiral phosphorescent probes for amino acids: hybrids of iridium(iii) complexes with synthetic saponite
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An attempt of developing a chiral luminescent probe for amino acids was described. Two types of chiral iridium(iii) complexes were synthesized: [Ir(dfppy)2(R-pep-bpy)]+ (dfppyH = 2-(2′,4′-difluorophenyl)pyridine); R-pep-bpy = 4,4′-bis((R-1,2-dimethylpropyl)aminocarbonyl-2,2′-bipyridine) and [Ir(piq)2(R-pep-bpy)]+ (piqH = 1-phenyisoquinoline). In both complexes, amido groups (R-pep-) were attached to 2,2′-bipyridine with an intension of increasing the affinity for an amino acid. The complexes were optically resolved on a chiral column. When the complexes were adsorbed by the colloidal particles of synthetic saponite, they were highly emissive even in a medium containing water. The remarkable quenching of emission was observed for the combination of [Ir(dfppy)2(R-pep-bpy)]+ and tryptophan methyl ester. By the use of the enantiomeric complexes, the possibility of enantioselective quenching was examined for various amino acid derivatives.
- Sato, Hisako,Tamura, Kenji,Yajima, Tomoko,Sato, Fumi,Yamagishi, Akihiko
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- In situ formation of AuNPs using fatty N-acylamino hydrazide organogelators as templates
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This work reports, for the first time, the synthesis of new fatty N-acylamino hydrazides and demonstrates the activity of these compounds as low-molecular-weight organic gelators and templates for preparation of gold nanoparticles (AuNPs). Initially, we evaluated the gelation properties of fatty N-acylamino hydrazides in various nonpolar and polar solvents (n-hexane, toluene, benzene, cyclohexane, and ethanol). Fatty N-acylamino hydrazide derived of the glycine and stearic acid (C18:0) did not form gels in any of the tested solvents. All other hydrazides did form gels in at least two of the organic solvents tested. The morphology of each gel was observed via scanning electron microscopy. The organogels derived from alanine, valine, and phenylalanine had translucid properties, while the serine organogels were opaque. Afterwards, the synthesis of AuNPs in the presence of the organogelator using microwave irradiation was realized. Organogelator agents reduced HAuCl4 showing plasmon band peaks between 530 and 543 nm. In addition, the method does not require a reducing agent, which is typically a potential source of contamination and toxicity. Therefore, this work confirms the importance of the hydrazide group of the new fatty N-acylamino hydrazides in gel formation and as organogelator agents for preparation of AuNPs.
- Ongaratto, Renata,Conte, Naiane,Montes D'Oca, Caroline R.,Brinkerhoff, Rafael C.,Ruas, Caroline Pires,Gelesky, Marcos Alexandre,Montes D'Oca, Marcelo G.
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- Phosphorylthioureas and phosphorylureas containing amino acid fragments
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A series of (dialkoxyphosphoryl)thioureas and their 1,3,2-oxazaphosphinane analogs containing fragments of glycine, alanine, ss-alanine, L-aspartic and L-glutamic acids, as well as phosphorylureas derived from glycine and ss-alanine were synthesized in the search for potential biologically active compounds (including possible inhibitors of aspartate trans-carbamoylase).
- Shipov,Genkina,Petrovskii
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- Synthesis and biological evaluation of N-(2-fluorophenyl)-2β- deoxyfuconojirimycin acetamide as a potent inhibitor for α-L-fucosidases
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In this study we revealed that the addition of an N-phenylacetamide substituent to the C-1 position of 1-deoxyfuconojirimycin (DFJ) can lead to highly potent inhibitors of α-l-fucosidases. A structure-activity relationship study showed that a fluoro group on the phenyl ring greatly increased its potency and selectivity. In contrast the addition of two or three fluoro groups decreased their inhibition potency. Consequently, N-(2-fluorophenyl)-2β-DFJ acetamide (18j) was found to display very potent and selective inhibition of bovine kidney, rat epididymis, and human lysosome α-l-fucosidases, with IC50 value of 0.012, 0.044, and 0.0079 μM respectively. It is noteworthy that our designed N-phenyl-2β-DFJ acetamide derivative exhibited about 18-fold stronger effects on human lysosomal α-l-fucosidase than original DFJ and it occupied the active-site of this enzyme. We therefore expect that this compound may find applications in new therapeutic trials against genetic deficiency disorders.
- Kato, Atsushi,Okaki, Toru,Ifuku, Syohei,Sato, Kasumi,Hirokami, Yuki,Iwaki, Ren,Kamori, Akiko,Nakagawa, Shinpei,Adachi, Isao,Kiria, Peter G.,Onomura, Osamu,Minato, Daishiro,Sugimoto, Kenji,Matsuya, Yuji,Toyooka, Naoki
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- New strategies for an efficient removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the peptide synthesis
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The aluminium trichloride/toluene system is investigated as a novel, unusual and straightforward reagent for the removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the solution peptide synthesis. This procedure avoids any undesired side reactions, such as the frequently observed inversion of the amino acid configuration.
- Leggio, Antonella,Liguori, Angelo,Napoli, Anna,Siciliano, Carlo,Sindona, Giovanni
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- Concentration-dependent dye aggregation and disassembly triggered by the same artificial helical foldamer
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Constructing and regulating the cyanine dye aggregates have been constantly pursued because of their wide applications in photosensitizers, biological fluorescence probes, nonlinear optics, etc. However, to realize such a process using a single additive still remains a formidable challenge. Here, the aggregation and disassembly of positively charged 3,3-diethyloxadicarbocyanine iodide (DiOC2(5)) have been demonstrated just by changing the concentration of an artificial poly(phenylenediethynylene)-based helical foldamer (Poly-1) bearing L-alanine sodium pendants with an amide linker. Poly-1 possessed the negatively charged pendants and hydrophobic helical grooves. Upon simple mixing of equal DiOC2(5) and Poly-1, DiOC2(5) molecules were mainly enriched on Poly-1 surface driven by electrostatic interaction and arranged along the main chain of Poly-1, resulting in the formation of chiral H-aggregates. But, the excessive Poly-1 would attract some DiOC2(5) molecules in H-aggregates via electrostatic interaction. The isolated monomers were easy to orderly disperse into the helical grooves due to hydrophobic interaction. Meanwhile, during the aggregation and disassembly, the solution color changed from peachblow to purple red and then to purple and finally to navy blue.
- Qiu, Yuan,Hu, Haisi,Zhao, Dongxu,Wang, Jing,Wang, Hong,Wang, Qin,Peng, Haiyan,Liao, Yonggui,Xie, Xiaolin
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- Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives
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Pyrimidine antimetabolic agents are the essential drugs in treatment of various tumors. Novel synthesis and biological evaluation of the pyrimidine derivatives incorporating selenium element and amino acid carrier as potential antitumor agents have not been tried and studied. Based on the biological significance of pyrimidine structure, these two additional elemental fragments maybe enhance the antitumor effect and reduce toxic side effects of pyrimidine agents. The aim of this paper is to synthesis a series of 4-selenopyrimidine derivatives in order to find more potent lead compounds against cancer. In this study, 12 new 4-selenopyrimidine derivatives that are unstable in acidic solutions but very stable in alkaline and neutral solutions avoiding light were synthesized, and the antitumor activities on HepG2 cell lines of these compounds were evaluated by MTT assay. The results have shown that these compounds could reduce the proliferation of HepG2 cells in a dose-dependent fashion, and the inhibitory activity of compounds a6 was greater than that of positive control 5-fluorouracil (5-FU), the IC50 for a6 was 3.63 μM. In the comprehensive analysis of the structure–activity relationship, we could draw the antitumor effect of selenouracil derivatives is stronger than those of selenothymine derivatives. These results suggest that the substituent groups of selenium element and amino acid on the pyrimidine derivatives are vital for their antitumor activities on HepG2 cells.
- Shi, Mingxing,Wang, Libo,Zhang, Long,Wang, Kexin,Zhang, Hualin,Wang, Yajing,Li, Chang,Han, Weina
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- Imines derived from 4-methyl-4-diphenylphosphorylpentan-2-one and potassium salts of aminocarboxylic acids
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An effective procedure for the preparation of imines based on 4-methyl-4-diphenylphosphorylpentan-2-one, aminoacetic, aminopropionic, and aminobutyric acids with yields of 90–95% was developed. Reaction of dimephosphone (4-methyl-4-dimethoxyphosphorilpent
- Dimukhametov,Mironov,Tatarinov
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- Flow 1H nmr study of the rapdid nucleophilic addition of amino acids to 4-formylpyridine
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Rapid addition of primary amino acids and imidazole to 4-formylpyridine to form carbinolamine intermediates in water has been studied by means of stopped-flow 1H nuclear magnetic resonance spectroscopy.The equilibrium constant Kn for this process was determined using stopped-flow uv spectroscopy.For the amino acid D,L-alanine and its derivatives , D,L-alanine methyl ester and D,L-alanylglycine Kn does not appear to correlate with Ka, the acid dissociation constant.Values of kn, the addition rate constant, appear to be independent of pH and bufferconcentration fo these nucleophiles.The limited data indicate that the variation in rates of nucleophilic addition to 4-formylpyridine cannot be accounted for in terms of pKa, Kn or related to systematic changes in structure of the nucleophile.As a group, the primary amino acid D,L-alanine and its derivatives have comparable kn values within a factor of two in spite of their different pKa values.Imidazole, an aromatic secondary diamine, has a kn value that is 10 to 20 times larger than these primary amines and has a relatively small Kn value.At the same time , its kn value is comparable to that found previously for sarcosine, a secondary acyclic amino acid having substantially larger pKa and Kn values.The nucleophilic addition step of primary amino acid and derivatives is rapid relative to the subsequent dehydration and prototropic shift steps.It occurs in a pH range at which pyridine nitrogen protonation is negligible.
- Tan, Liang K.,Cocivera, Michael
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- A Facile Synthesis of α-Amino Esters via Reduction of α-Nitro Esters Using Ammonium Formate as a Catalytic Hydrogen Transfer Agent
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Various nitroesters 3 were selectively and rapidly reduced to their corresponding amino esters 4 in very good yield using anhydrous ammonium formate as a catalytic hydrogen transfer agent.
- Ram, Siya,Ehrenkaufer, Richard E.
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- A mild and convenient procedure for the esterification of amino acids
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Chiral amino acids are esterified in high yield and purity at room temperature by stirring with amberlyst-15 in alcohols.
- Anand, Ramesh C.,Vimal
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- Synthesis and molecular recognition of novel multiimidazole cyclophanes
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(Chemical Equation Presented) Cyclophanes based on 2,2′-biimidazole and 2,2′-bibenzimidazole were synthesized as receptors. UV spectroscopic titration in chloroform at 25°C showed 1:1 complexes between the cyclophanes and the guests, and the binding constants (K) and Gibbs free energy changes (-ΔG0) were calculated according to the modified Benesi-Hildebrand equation.
- Xu, Xiao-Wei,Wang, Xin-Long,Wu, Ai-Ming,Zheng, Zhi-Ming,Yi, Mei-Gui,Xiao, Rong
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- A prodrug resistance mechanism is involved in colibactin biosynthesis and cytotoxicity
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Commensal Escherichia coli residing in the human gut produce colibactin, a small-molecule genotoxin of unknown structure that has been implicated in the development of colon cancer. Colibactin biosynthesis is hypothesized to involve a prodrug resistance strategy that entails initiation of biosynthesis via construction of an N-terminal prodrug scaffold and late-stage cleavage of this structural motif during product export. Here we describe the biochemical characterization of the prodrug synthesis, elongation, and cleavage enzymes from the colibactin biosynthetic pathway. We show that nonribosomal peptide synthetases ClbN and ClbB assemble and process an N-acyl-d-asparagine prodrug scaffold that serves as a substrate for the periplasmic d-amino peptidase ClbP. In addition to affording information about structural features of colibactin, this work reveals the biosynthetic logic underlying the prodrug resistance strategy and suggests that cytotoxicity requires amide bond cleavage.
- Brotherton, Carolyn A.,Balskus, Emily P.
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- New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy
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There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (ΔaX) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α′-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α′)-C?H bond. In buffer, the three main hfs (aN, aH, and aP) of their EPR spectra vary reversibly with pH and, from aP or aH titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pKa ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers.
- Thétiot-Laurent, Sophie,Gosset, Ga?lle,Clément, Jean-Louis,Cassien, Mathieu,Mercier, Anne,Siri, Didier,Gaudel-Siri, Anouk,Rockenbauer, Antal,Culcasi, Marcel,Pietri, Sylvia
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- Quantitative enzymatic protection of D-amino acid methyl esters by exploiting 'relaxed' enantioselectivity of penicillin-G amidase in organic solvent
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A quantitative method for enzymatic protection of esters of various d-amino acids in organic solvent is reported. The lower enantioselectivity displayed by penicillin-G amidase (PGA) from E. coli in organic solvent has been exploited for developing a facile, fast and quantitative method for protection of esters of various d-amino acids via N-acylation. The feasibility of the deprotection of the acylated products was also demonstrated by employing PGA from two different sources in aqueous media. Experimental results are in agreement with previous calculations based on in silico models of the enzyme active site.
- Carboni, Chiara,Quaedflieg, Peter J. L. M.,Broxterman, Quirinus B.,Linda, Paolo,Gardossi, Lucia
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- Ceric ammonium nitrate (CAN) mediated esterification of N-Boc amino acids allows either retention or removal of the N-Boc group
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Reaction of N-Boc amino acids with ceric ammonium nitrate in an alcohol as the solvent at room temperature resulted in the esterification of N-Boc amino acids with Boc group retention. When the reaction was conducted at reflux temperature, esterification was accompanied with simultaneous removal of the Boc group. Both reactions gave the desired products in good yields.
- Kuttan, Ashani,Nowshudin, Shiek,Rao
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- Pyrroloisoxazoles as a building block for 3-enoyltetramic acids
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3-Methylpyrrolo[3,4-c]isoxazoles prepared by nitrile oxide cycloaddition, are deprotonated and condensed with aromatic aldehydes; N-O bond cleavage with Mo(CO)6 affords 3-enoyltetramic acids whilst with H 2-catalyst further reduction to 3-acyltetramic acids is observed.
- Jones, Raymond C. F.,Pillainayagam, Terence A.
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- Esterification of amino acids and mono acids using triphosgene
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Alkyl esters of several amino acids and acids were prepared using triphosgene [trichloromethyl carbonate, TPA (2)].
- Rivero,Heredia,Ochoa
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- Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid
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This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.
- Di Gioia,Barattucci,Bonaccorsi,Leggio,Minuti,Romio,Temperini,Siciliano
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- Crucigasterins, New Polyunsaturated Amino Alcohols from the Mediterranean Tunicate Pseudodistoma crucigaster
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Crucigasterins 277, 275, and 225, three new polyunsaturated amino alcohols, 10-12, were isolated from the Mediterranean tunicate Pseudodistoma crucigaster.The structures of these compounds were assigned based on NMR and FABMS data.Absolute stereochemistry of the amino alcohol portion in 10 was assigned to be 2R,3S based on chiral GC comparison of 3-hydroxy-4-aminopentanoic acid 13d, a chemical degradation product of 10, with a synthetic sample prepared from L-alanine.Compounds 10-12 exhibited moderate cytotoxicity and antimicrobial activity.
- Jares-Erijman, Elizabeth A.,Bapat, Chintamani P.,Lithgow-Bertelloni, Anna,Rinehart, Kenneth L.,Sakai, Ryuichi
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- Controlled drug delivery from mesoporous silica using a pH-response release system
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Mesoporous hollow silica nanoparticles were functionalized with phenanthroline (P-MHS) to prepare a carrier for a host-guest complex. Curcumin was selected as a model drug molecule. The phenanthroline attached to the P-MHS was complexed with Cu2+ through a coordination bond. When the Cu 2+-P-MHS was exposed to ~pH 5, the curcumin was efficiently released into the aqueous phase within 120 min. This work describes a method for functionalizing the surface of the porous silica nanoparticles in a well-defined manner. The P-MHS carrier exhibited controlled release of a model drug under acidic pH conditions.
- Jin, Dalsaem,Lee, Ji Ha,Seo, Moo Lyong,Jaworski, Justyn,Jung, Jong Hwa
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- Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors
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A novel series of N-methylmaleimide indolocarbazole derivatives bearing modified 2-acetamino acid moieties are first reported. The cytotoxic effects of these compounds were tested in five human tumor cell lines. The potent compounds 9a, 9b, 9d, and 9e have been further evaluated for their effect on Topoisomerase I (TOPO I) and cancer cell cycle. It is concluded that the indolocarbazoles with alkyl piperazine or morpholine substituent groups instead of esters or glycosyl residues would have better activities against tumors.
- Li, Zhiyu,Zhai, Fuming,Zhao, Li,Guo, Qinglong,You, Qidong
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- Asperelines A-F, peptaibols from the marine-derived fungus Trichoderma asperellum
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Fermentation of the marine-derived fungus Trichoderma asperellum, collected from the sediment of the Antarctic Penguin Island, resulted in the isolation of six new peptaibols named asperelines A-F (1-6), which are characterized by an acetylated N-terminus and a C-terminus containing an uncommon prolinol residue. Structures were determined by extensive 1D and 2D NMR (1H- 1H COSY, HMQC, HMBC, NOESY) spectroscopic data analysis combined with ESIMS/MS fragmentation. The absolute configurations of the amino acid residues possessing a chiral R-carbon and of the prolinol residue were determined to be L and S, respectively, using a new method of 1H NMR spectroscopic comparison of complexes formed between the chiral reagent Ru(D 4-Por*)CO and amino acids derived from the peptaibols with those formed with reference standards.
- Ren, Jinwei,Xue, Chunmei,Tian, Li,Xu, Minjuan,Chen, Jian,Deng, Zhiwei,Proksch, Peter,Lin, Wenhan
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- Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host?Guest Complexes with a Bis(zinc porphyrin) Tweezer
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A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.
- Olsson, Sandra,Sch?fer, Clara,Blom, Magnus,Gogoll, Adolf
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- Reaction of Ketene Silyl Acetals with Diazonium Salts: a Novel α-Amino Acid Ester Synthesis
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The reaction of ketene silyl acetals with arenediazonium tetrafluoroborate gave α-hydrazono and α-azo esters, which were easily hydrogenated to α-amino esters.
- Sakakura, Toshiyasu,Tanaka, Masato
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- Synthesis and biological evaluation of novel lipoamino acid derivatives
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Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8 μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50 = 15.3-22.4 μM) against the four cell lines tested.
- Kaki, Shiva Shanker,Arukali, Sammaiah,Korlipara, Padmaja V.,Prasad,Yedla, Poornachandra,Ganesh Kumar
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- A novel and facile method to synthesize (R)- and (S)-2-methylpiperazine
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A concise and efficient synthesis of (R)- and (S)-2-methylpiperazine in only five steps from (D)- and (L)-alanine is described. The key step is reaction of benzylamine with a bifunctional molecule to build a six-membered ring.
- Liu, Bo,Xu, Guang-Yu,Yang, Chun-Hao,Wu, Xi-Han,Xie, Yu-Yuan
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- A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters
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A stereo-divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium-catalyzed N-allylation of α-amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)-2-penten-4-yl carbonate in the presence of only 1 mol% of a catalyst, prepared in-situ from the C2-symmetric diphosphine iPr-MediPhos and [Pd(allyl)Cl]2. Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N-allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N-Boc-protection.
- Albat, Dominik,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
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supporting information
p. 2099 - 2102
(2021/07/22)
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- Light-Induced Formation/Scission of C-N, C-O, and C-S Bonds Enables Switchable Stability/Degradability in Covalent Systems
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The manipulation of covalent bonds could be directed toward degradable, recyclable, and sustainable materials. However, there is an intrinsic conflict between properties of stability and degradability. Here we report light-controlled formation/scission of three types of covalent bonds (C-N, C-O, and C-S) through photoswitching between equilibrium and nonequilibrium states of dynamic covalent systems, achieving dual benefits of photoaddressable stability and cleavability. The photocyclization of dithienylethene fused aldehyde ring-chain tautomers turns on the reactivity, incorporating/releasing amines, alcohols, and thiols reversibly with high efficiency, respectively. Upon photocycloreversion the system is shifted to kinetically locked out-of-equilibrium form, enabling remarkable robustness of covalent assemblies. Reaction coupling allows remote and directional control of a diverse range of equilibria and further broadens the scope. Through locking and unlocking covalent linkages with light when needed, the utility is demonstrated with capture/release of bioactive molecules, modification of surfaces, and creation of polymers exhibiting tailored stability and degradability/recyclability. The versatile toolbox for photoswitchable dynamic covalent reactions to toggle matters on and off should be appealing to many endeavors.
- Hai, Yu,Li, Ziyi,Lu, Hanwei,Ye, Hebo,You, Lei,Zou, Hanxun
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supporting information
p. 20368 - 20376
(2021/12/03)
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- N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
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Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
- Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
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- Design, synthesis and evaluation of the antibacterial activity of new Linezolid dipeptide-type analogues
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Worldwide studies towards development of new drugs with a lower rate in emergence of bacterial resistance have been conducted. The molecular docking analysis gives a possibility to predict the activity of new compounds before to perform their synthesis. In this work, the molecular docking analysis of 64 Linezolid dipeptide-type analogues was performed to predict their activity. The most negative scores correspond to six Fmoc-protected analogues (9as, 9bs, 9bu, 10as, 10ax and 10ay) where Fmoc group interacts in PTC for Linezolid. Twenty-six different Fmoc-protected Linezolid dipeptide-type analogues 9(as-bz) and 10(as-bz) were synthesized and tested in antimicrobial experiments. Compounds 9as, 9ay, 9ax, 10as, 10ay and 9bu show significant activity against group A Streptococcus clinical isolated. Analogue 10ay also display high activity against ATCC 25923 Staphylococcus aureus strain and MRSA-3, MRSA-4 and MRSA-5 clinical isolates, with MIC values lower than Linezolid. The highest activity against multidrug-resistant clinical isolates of Mycobacterium tuberculosis was exhibited by 9bu. Finally, a cytotoxicity assay with ARPE-19 human cells revealed a non-cytotoxic effect of 9bu and 10ay at 50 and 25 μM, respectively.
- García-Olaiz,Alcántar-Zavala, Eleazar,Ochoa-Terán, Adrián,Cabrera, Alberto,Mu?iz-Salazar, Raquel,Montes-ávila, Julio,Salazar-Medina, Alex J.,Alday, Efrain,Velazquez, Carlos,Medina-Franco, José L.,Laniado-Laborín, Rafael
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supporting information
(2019/12/23)
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- Urethanes synthesis from oxamic acids under electrochemical conditions
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Urethane synthesis via oxidative decarboxylation of oxamic acids under mild electrochemical conditions is reported. This simple phosgene-free route to urethanes involves an in situ generation of isocyanates by anodic oxidation of oxamic acids in an alcoholic medium. The reaction is applicable to a wide range of oxamic acids, including chiral ones, and alcohols furnishing the desired urethanes in a one-pot process without the use of a chemical oxidant.
- Ogbu, Ikechukwu Martin,Lusseau, Jonathan,Kurtay, Gülbin,Robert, Frédéric,Landais, Yannick
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supporting information
p. 12226 - 12229
(2020/10/26)
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- Cleavable Amide Bond: Mechanistic Insight into Cleavable 4-Aminopyrazolyloxy Acetamide at Low pH
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The cleavage of amide bonds under mild acidic conditions is a rare chemical event. N-Acetamide bond of peptides is extremely stable even under the strongest organic acid trifluoromethanesulfonic acid. This report mechanistically describes a new cleavable amide bond in 4-aminopyrazolyloxy acetamide peptide analogues under mild acidic conditions such as trifluoroacetic acid (10-20%) or HCl (0.1-4.0 N) at room temperature, and the formation of unusual lactam from 4-aminopyrazolyloxy acetic acid after evaporation of solvent. This is a rare chemical event in peptide bond, which could be explored as acid-sensitive protecting group of free amines.
- Bollu, Amarnath,Sharma, Nagendra K.
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supporting information
(2019/05/08)
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- Visible-light mediated carbamoyl radical addition to heteroarenes
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The generation of carbamoyl radicals, followed by their addition to heteroarenes, was performed under mild conditions through a metal-free photocatalyzed decarboxylation of oxamic acids. The process has been applied to the carbamoylation of heteroaromatic bases using α-aminoacid-derived oxamic acids, leading to the corresponding amides without racemization.
- Jatoi, Ashique Hussain,Pawar, Govind Goroba,Robert, Frédéric,Landais, Yannick
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supporting information
p. 466 - 469
(2019/01/10)
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- Resveratrol amino acid ester derivative and preparation method thereof
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The invention discloses a resveratrol amino acid ester derivative and a preparation method thereof, and belongs to the technical field of fine chemical substance synthesis. The structure of the resveratrol amino acid ester derivative is represented by a formula shown in the description. The resveratrol amino acid ester derivative is synthesized from resveratrol, R amino acid, R' alcohol, dichlorosulfoxide and di(p-nitrobenzene) carbonate with 4-dimethylaminopyridine (DMAP) as a catalyst and acetonitrile as a solvent, wherein the R amino acid is one of alpha-alanine, beta-alanine and gamma-aminobutyric acid, and the R' alcohol is one of methanol, ethanol and n-propanol. The technical problem that resveratrol is difficult to preserve is solved, the pharmacological toxicity introduced by a resveratrol substituent group is lowered, and the resveratrol amino acid ester derivative has the pharmaceutical effects of resveratrol and amino acid. It is expected that the above novel compound playsa great role in beauty treatment and production of fatigue-relieving and blood pressure-lowering medicines.
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Paragraph 0059-0065
(2019/07/04)
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- Design, synthesis, and molecular docking studies of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives as xanthine oxidase inhibitors
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A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L-phenylalanine derivative 1d (IC50?=?3.0?μm) and the D-phenylalanine derivative 1i (IC50?=?2.9?μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50?=?8.1?μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D-amino acid derivative presented equal or greater potency compared to its L-enantiomer; and the 9,10-anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
- Zhang, Ting-Jian,Li, Song-Ye,Yuan, Wei-Yan,Zhang, Yi,Meng, Fan-Hao
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p. 893 - 901
(2018/03/21)
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- 6,7-DIHYDRO-4H-PYRAZOLO[1,5-A]PYRAZINE COMPOUNDS FOR THE TREATMENT OF INFECTIOUS DISEASES
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The present invention relates to compounds of the formula (I) or pharmaceutically acceptable salts, enantiomer or diastereomer thereof, wherein R1 to R4 are as described above. The compounds may be useful for the treatment or prophylaxis of hepatitis B virus infection.
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Page/Page column 36
(2018/03/26)
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- Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors
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The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.
- Liu, Shuai,Yosief, Hailemichael O.,Dai, Lingling,Huang, He,Dhawan, Gagan,Zhang, Xiaofeng,Muthengi, Alex M.,Roberts, Justin,Buckley, Dennis L.,Perry, Jennifer A.,Wu, Lei,Bradner, James E.,Qi, Jun,Zhang, Wei
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p. 7785 - 7795
(2018/09/13)
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- Unlocking the potential of phenacyl protecting groups: CO2-based formation and photocatalytic release of caged amines
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Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy)3](PF6)2-catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples.
- Speckmeier, Elisabeth,Klimkait, Michael,Zeitler, Kirsten
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p. 3738 - 3745
(2018/04/14)
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- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00445
(2017/10/06)
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- Method for preparing amino ether compounds
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The invention belongs to the technical field of organic synthesis and relates to a method for preparing amino ether compounds. The method comprises the following steps: by taking amino alcohol as a raw material, protecting amino in the amino alcohol so as to obtain Schiff base; carrying out an etherification reaction on the hydroxyl group in the Schiff base; and finally, performing amino deprotection, thereby obtaining corresponding amino ethers. The method disclosed by the invention has high regio-selectivity, the substrates of higher than 99.9% are subjected to etherification reaction, the reaction conversion ratio of each step is higher than 99.8%, and the total yield is higher than 95%; when amino alcohol is chiral, the amino ethers with retention of configuration can be obtained; and moreover, each step of the method is a conventional operation, the process cost is low, and three wastes are few, the energy consumption is low, an environment-friendly effect is achieved, and large-scale industrial production is easily realized.
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Paragraph 0071; 0074; 0075
(2017/08/26)
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- Enantiomerically pure piperazines via NaBH4/I2reduction of cyclic amides
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Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (3S,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine.
- Harish, Vagala,Periasamy, Mariappan
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p. 175 - 180
(2017/01/11)
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- Simple and efficient Fmoc removal in ionic liquid
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A mild method for an efficient removal of the fluorenylmethoxycarbonyl (Fmoc) group in ionic liquid was developed. The combination of a weak base such as triethylamine and [Bmim][BF4] makes the entire system more efficient for the cleavage at room temperature of various amines and amino acid methyl esters in short reaction times. The procedure works well even in the case of N-Fmoc amino acids bearing acid-sensitive protecting groups and of N-alkylated amino acid methyl esters. The solvent-free condition provides a complementary method for Fmoc deprotection in solution phase peptide synthesis and modern organic synthesis.
- Di Gioia,Costanzo,De Nino,Maiuolo,Nardi,Olivito,Procopio
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p. 36482 - 36491
(2017/08/02)
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- Hydroxy-Directed Amidation of Carboxylic Acid Esters Using a Tantalum Alkoxide Catalyst
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We describe herein a new strategy for the chemoselective synthesis of amides by using a metal-catalyzed hydroxy-directed reaction. A hydroxy group located at the β-position of an ester group promoted the activation of a carbonyl group with a tantalum alkoxide catalyst followed by amidation reactions, leading to a wide variety of β-hydroxyamides with excellent chemeselectivity. The chemoselective amidation strategy can be extended to the catalytic synthesis of dipeptide derivatives, which remains challenging research subjects in modern organic synthesis.
- Tsuji, Hiroaki,Yamamoto, Hisashi
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supporting information
p. 14218 - 14221
(2016/11/13)
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- Design, synthesis of new chiral fluorine-containing β-hydroxysulfonamides from natural amino acids and study of their anti-inflammatory and analgesic activities
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A series of new chiral fluorine-containing β-hydroxysulfonamides were conveniently synthesized in three steps, starting from natural L-amino acids, and evaluated for their anti-inflammatory and analgesic activities. The structures of these compounds were supported by FT-IR, 1H, 13C and 19F NMR, elemental analysis and HRMS. Among the tested compounds, 4c, 4g and 4h exhibited promising anti-inflammatory activity. Moreover, compound 4h showed a significant analgesic activity. The structure–activity relationships of selected compounds were discussed.
- Gloulou, Monia,Kra?em, Jamil,Jennene, Fay?al,Ghedira, Donia,Amor, Haifa Bel Haj,Lajili, Sirine,Jalleli, Emna,Ferjani, Maha,Bouraoui, Abderrahman,Kallel, Mohamed
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p. 1497 - 1506
(2016/07/06)
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- P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS
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The present application provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R4 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient.
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Paragraph 0209; 0210; 0211
(2015/07/07)
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- CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.
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Page/Page column 148
(2015/12/17)
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- Pyrene-based fluorescent ambidextrous gelators: Scaffolds for mechanically robust swnt-gel nanocomposites
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With the rapid progress in the development of supramolecular soft materials, examples of low-molecularweight gelators (LMWGs) with the ability to immobilise both water and organic solvents by the same structural scaffold are very limited. In this paper, we report the development of pyrene-containing peptide-based ambidextrous gelators (AGs) with the ability to efficiently gelate both organic and aqueous solvents. The organo-and hydrogelation efficiencies of these gelators are in the range 0.7-1.1% w/v in various organic solvents and 0.5-5% w/v in water at certain acidic pH values (pH 2.0-4.0). Moreover, for the first time, AGs have been utilised to prepare single-walled carbonnanotube (SWNT)-included soft nanocomposites in both hydro-and organogel matrices. The influence of different non-covalent interactions such as hydrogen bonding, hydrophobic, p-p and van der Waals interactions in self-assembled gelation has been studied in detail by circular dichroism, FTIR, variable-temperature NMR, 2D NOESY and luminescence spectroscopy. Interestingly, the presence of the pyrene moiety in the structure rendered these AGs intrinsically fluorescent, which was quenched upon successful integration of the SWNTs within the gel. The prepared hydroand organogels along with their SWNT-integrated nanocomposites are thermoreversible in nature. The supramolecular morphologies of the dried gels and SWNT-gel nanocomposites have been studied by transmission electron microscopy, fluorescence microscopy and polarising optical microscopy, which confirmed the presence of three-dimensional self-assembled fibrillar networks (SAFINs) as well as the integrated SWNTs. Importantly, rheological studies revealed that the inclusion of SWNTs within the ambidextrous gels improved the mechanical rigidity of the resulting soft nanocomposites up to 3.8-fold relative to the native gels.
- Mandal, Deep,Kar, Tanmoy,Das, Prasanta Kumar
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p. 1349 - 1358
(2014/04/03)
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- A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
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An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
- Bera, Saurav,Panda, Gautam
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p. 3976 - 3985
(2014/06/09)
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- Synthesis of peptides employing protected-amino acid halides mediated by commercial anion exchange resin
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Coupling of protected-amino acid halides (chloride, fluoride) mediated by commercial anion exchange resin for the solution phase synthesis of peptides is described. The reaction was carried out in an organic medium, circumventing the use of an organic base or an inorganic base. The coupling is fast, clean and racemization free. The anion exchange resin functions as a solid-phase basic scavenger, soaking up the HCl produced and allowing the amine to react. The method is extended for the coupling of sterically hindered α,α,- dialkylamino acids. Graphical Abstract: [Figure not available: see fulltext.]
- Bhaskara Redddy,Kumari, Y. Bharathi,Ananda, Kuppanna
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p. 225 - 229
(2013/12/04)
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- Enantioselective synthesis of 1,2,4-triazolines by chiral iron(ii)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates
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Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by FeII-N,N′-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities.
- Wang, Min,Liu, Xiaohua,He, Peng,Lin, Lili,Feng, Xiaoming
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supporting information
p. 2572 - 2574
(2013/04/10)
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- Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): Discovery of 5-((3-fluorophenyl)ethynyl)- N -(3-methyloxetan-3-yl)picolinamide (ML254)
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Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Both allosteric agonism and high glutamate fold-shift have been implicated in the neurotoxic profile of some mGlu5 PAMs; however, these hypotheses remain to be adequately addressed. To develop tool compounds to probe these hypotheses, the structure-activity relationship of allosteric agonism was examined within an acetylenic series of mGlu5 PAMs exhibiting allosteric agonism in addition to positive allosteric modulation (ago-PAMs). PAM 38t, a low glutamate fold-shift allosteric ligand (maximum fold-shift ~3.0), was selected as a potent PAM with no agonism in the in vitro system used for compound characterization and in two native electrophysiological systems using rat hippocampal slices. PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs.
- Turlington, Mark,Noetzel, Meredith J.,Chun, Aspen,Zhou, Ya,Gogliotti, Rocco D.,Nguyen, Elizabeth D.,Gregory, Karen J.,Vinson, Paige N.,Rook, Jerri M.,Gogi, Kiran K.,Xiang, Zixiu,Bridges, Thomas M.,Daniels, J. Scott,Jones, Carrie,Niswender, Colleen M.,Meiler, Jens,Jeffrey Conn,Lindsley, Craig W.,Stauffer, Shaun R.
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p. 7976 - 7996
(2013/11/06)
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- HR-MALDI-MS imaging assisted screening of β-Carboline alkaloids discovered from mycena metata
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Fruiting bodies of Mycena metata were screened for the presence of new secondary metabolites by means of HPLC-UV, LC-HR-ESIMS, and high-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (HRMALDI- MS imaging). Thus, a new β-carboline alkaloid, 6-hydroxymetatacarboline D (1d), was isolated from fruiting bodies of M. metata. 6-Hydroxymetatacarboline D consists of a highly substituted β-carboline skeleton, which is likely to be derived biosynthetically from L-tryptophan, 2-oxoglutaric acid, L-threonine, and L-proline. The structure of the alkaloid was established by 2D NMR spectroscopic methods and HR-ESIMS. Moreover, by extensive application of LC-HR-ESIMS, LC-HR-ESIMS/MS, and LC-HR-ESIMS3 techniques we were able to elucidate the structures of a number of accompanying β-carboline alkaloids, 1a- 1c, 1e-1i, and 2a-2g, structurally closely related to 6-hydroxymetatacarboline D, which are present in M. metata in minor amounts. The absolute configuration of the stereogenic centers of the β-carboline alkaloids was determined by GC-MS comparison with authentic synthetic samples after hydrolytic cleavage and derivatization of the resulting amino acids.
- Jaeger, Robert J. R.,Lamshoeft, Marc,Gottfried, Sebastian,Spiteller, Michael,Spiteller, Peter
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p. 127 - 134
(2013/06/27)
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- N-alkylcarbonyl-amino acid ester compounds and their use for cough and pharyngitis
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The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino acid esters compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of reducing cough and pharyngeal irritation, itch, and/or pain.
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- Evaluation of the binding ability of tetraaza[2]arene[2]triazine receptors anchoring l-alanine units for aromatic carboxylate anions
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The binding affinities of three new tetraaza[2]arene[2]triazine based macrocycles anchoring one (AC1A) and two (AC2A and Me4AC2A) l-alanine amino acid units for five aromatic carboxylate anions (bz-, ph 2-, iph2-, tph2- and btc3-) were investigated in DMSO-d6. 1H NMR titrations revealed that the AC1A and AC2A receptors exhibit comparable anion affinities, suggesting that the two l-alanine binding units in AC2A are not simultaneously involved in the anion recognition as indicated by molecular dynamics simulations carried out for selected AC1A and AC2A associations using the AMBER force field (GAFF). New force field parameters were developed in order to mimic the structural singularity derived from the N-H macrocyclic bridges.
- Vicente, Ana I.,Caio, Jo?o M.,Sardinha, Jo?o,Moiteiro, Cristina,Delgado, Rita,Félix, Vítor
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experimental part
p. 670 - 680
(2012/02/13)
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- I2-mediated diversity oriented diastereoselective synthesis of amino acid derived trans-2,5-disubstituted morpholines, piperazines, and thiomorpholines
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Diastereoselective trans-2,5-disubstituted amino acids derived diverse morpholines, piperazines and thiomorpholines were prepared in 30 min-1 h with high yields through iodine-mediated 6-exotrig type cyclization from a single common synthetic intermediate. The displacement of iodine with hydride ion gave a methyl substituent at the 2-position of morpholines which provides an additional opportunity for diversity oriented nucleophilic substitution on the rings as well as incorporation of substituents at the 5-position from amino acids constituents.
- Bera, Saurav,Panda, Gautam
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scheme or table
p. 1 - 4
(2012/02/16)
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- Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx
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Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.
- Kimura, Miki,Wakimoto, Toshiyuki,Egami, Yoko,Tan, Karen Co,Ise, Yuji,Abe, Ikuro
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experimental part
p. 290 - 294
(2012/05/05)
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