- Expeditious synthesis and assembly of sub-100 nm hollow spherical gold nanoparticle superstructures
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Sub-100 nm hollow gold nanoparticle superstructures were prepared in a direct one-pot reaction. A gold-binding peptide conjugate, C6-AA- PEPAu (PEPAu = AYSSGAPPMPPF), was constructed and used to direct the simultaneous synthesis and assembly of gold nanoparticles. Transmission electron microscopy and electron tomography revealed that the superstructures are uniform and consist of monodisperse gold nanoparticles arranged into a spherical monolayer shell.
- Song, Chengyi,Zhao, Gongpu,Zhang, Peijun,Rosi, Nathaniel L.
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- Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.
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Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC-ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1-3 and synthetic analogues 1a-e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD9931 μg/mL), with preliminary structure-activity relationship investigations confirming the importance of the N-acyl side chain.
- Farrugia, Michelle,Trotter, Nicholas,Vijayasarathy, Soumini,Salim, Angela A.,Khalil, Zeinab G.,Lacey, Ernest,Capon, Robert J.
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- N-hydroxysuccinimide-promoted oxidation of primary alcohols and aldehydes to form active esters with hypervalent(III) iodine
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A simple, mild, and efficient method for the conversion of primary alcohols and aldehydes to N-hydroxysuccinimide esters with (diacetoxyiodo)benzene in high yield is developed. N-Hydroxysuccinimide acts not only as an esterification partner but also as an activator of PhI(OAc)2 in this reaction. Copyright
- Wang, Naiwei,Liu, Renhua,Xu, Qing,Liang, Xinmiao
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- Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications
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The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (~50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ~200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.
- Sharma, Divya,Singh, Jagdish
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- SYNTHESIS AND BIOLOGICAL ACTIVITIES OF SOME PEPTIDOGLYCAN MONOMER DERIVATIVES
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N-acyl derivatives and N-acetyl-glucosaminyl-β-(1->4)-N-acetyl-muramoyl-L-alanyl-D-isoglutaminyl-L-meso-diaminopimelyl-(D-amide)-(L)-D-alanyl-D-alanine (peptidoglycan monomer, PGM) complexes with some bivalent metals were prepared and their immunomodulatory activities examined.
- Suskovic, B.,Vajtner, Z.,Naumski, R.
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Read Online
- Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis
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Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in Mtb. The precise biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and FACL enzymes. We identified several potent compounds including 12-azidododecanoyl-AMS 28, 11-phenoxyundecanoyl-AMS 32, and nonyloxyacetyl-AMS 36 with minimum inhibitory concentrations (MICs) against M. tuberculosis ranging from 0.098 to 3.13 μM. Compound 32 was notable for its impressive biochemical selectivity against FAAL28 (apparent Ki = 0.7 μM) versus FACL19 (Ki > 100 μM), and uniform activity against a panel of multidrug and extensively drug-resistant TB strains with MICs ranging from 3.13 to 12.5 μM in minimal (GAST) and rich (7H9) media. The SAR analysis provided valuable insights for further optimization of 32 and also identified limitations to overcome.
- Aldrich, Courtney C.,Baran, Marzena,Boshoff, Helena I. M.,Fu, Peng,Grimes, Kimberly D.,Sibbald, Paul A.,Wilson, Daniel J.
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- Deuterated eliglustat racemate synthetic process
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The invention belongs to the technical field of pharmaceutical synthesis, and in particular relates to a deuterated eleustat racemate synthetic process. The process includes a synthetic method of a key intermediate 2,3-dihydro-1,4-benzdioxan2,2,3,3-d4-6-a
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Paragraph 0038; 0072; 0073; 0074
(2019/01/16)
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- Synthesis of UDP-glucose: N-acylsphingosine glucosyl transferase inhibitors
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Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
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Page/Page column 24
(2017/02/09)
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- Method for preparing tartrate EGS
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The invention discloses a method for preparing tartrate EGS. The method comprises the following steps: (1) subjecting EGS-A4 represented by a formula shown in the description and trifluoroacetic acid to a reduction reaction in an inert atmosphere in the presence of a catalyst, so as to obtain EGS-SMA represented by a formula shown in the description after the reaction is complete, wherein the catalyst is Pd/C or the like; (2) preparing EGS-SMB represented by a formula shown in the description from EGS-B0 represented by a formula shown in the description, an acid binding agent and EGS-B0' represented by a formula shown in the description, then, subjecting the EGS-SMB to a reaction with the EGS-SMA so as to obtain EGS-API represented by a formula shown in the description, and then, subjecting the EGS-API to a reaction with L-tartaric acid, thereby obtaining the final product. The method can adapt to large-scale production processes and has the process characteristics of wide source, low cost and stable yield, and the yield of the obtained tartrate EGS is remarkably higher than that of the existing methods and can reach 95%, so that the method has an important application value.
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Paragraph 0096; 0097; 0098; 0099; 0100
(2017/07/31)
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- SURFACE FUNCTIONALIZED, HOST-GUEST POLYMER NANO-ASSEMBLIES AND METHODS THEREOF
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The invention generally relates to polymer-based nano-structures. More particularly, the invention relates to novel, surface-functionalized, guest-host polymer nano-assemblies and nano-delivery vehicles useful in diverse fields including drug delivery, diagnostics and specialty materials. The nano-assemblies and nano-delivery vehicles of the invention are afforded via simplify and reliable approaches.
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Paragraph 00118; 00122
(2015/09/28)
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- A systematic understanding of gelation self-assembly: solvophobically assisted supramolecular gelation via conformational reorientation across amide functionality on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid)
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A systematic investigation on gelation self-assembly has been performed on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid). To elucidate the effect of hydrophobic tuning on gelator architecture towards its gelation self-assembly, three sets of gelators with a common formula: CmH2m+1C(=O)NH(l)Val(C=O)NH-(CH2)n-(C=O)OBn, were synthesized, Set-I includes gelators with n = 2, m = 9, 11, 13, 15, 17, for Set-II it is n = 2, 3, 5, m = 13 and Set-III comprises of two isomeric gelators (n = 2, m = 15; n = 10, m = 7). Gelation has been critically analyzed in various apolar (aromatic and aliphatic) and polar (protic and aprotic) solvents using FESEM, CD, IR, WAXRD and rheological studies. Obtained results reveal that π-π type interaction dictates the primary molecular alignment and positioning of amide functionality across the aliphatic chain which influences the peptidic orientation in parallel (when m > n) or antiparallel (when m gel and yield stress of gel systems increases with m, but for a given m, the trend goes apparently inverse with the increasing n. Circular dichroism (CD) studies suggest an intriguing evidence of non-planarity of amide plane during self-assembly, highlighting the involvement of conformational change taking place during molecular organization towards its gelation. Despite complex nature of solvent-gelator interaction, the effect of H-bonding component of solubility parameters was found to have a significant role on self-assembly. Overall, supramolecular forces acting at specific functionalities encrypted in gelator backbone must overcome the solvation energy with synergic assistance of solvophobic effect towards stabilization of gel-network with optimum gelator backbone conformation for achieving required enthalpic contribution for self-assembly.
- Haldar, Saubhik,Karmakar, Koninika
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p. 66339 - 66354
(2015/08/18)
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- Synthesis of tris-hydroxymethyl-based nitrone derivatives with highly reactive nitronyl carbon
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A novel series of α-phenyl-N-tert-butyl nitrone derivatives, bearing a hydrophobic chain on the aromatic ring and three hydroxyl functions on the tert-butyl group, was synthesized through a short and convenient synthetic route based on a one-pot reduction/condensation of tris(hydroxymethyl)nitromethane with a benzaldehyde derivative. Because of the presence of hydroxyl functions on the tert-butyl group, an intramolecular Forrester-Hepburn reaction leading to the formation of an oxazolidine-N-oxyl compound was observed by electron paramagnetic resonance (EPR). The mechanism of cyclization was further studied by computational methods showing that intramolecular hydrogen bonding and high positive charge on the nitronyl carbon could facilitate the nucleophilic addition of a hydroxyl group onto the nitronyl carbon. At high nitrone concentrations, a second paramagnetic species, very likely formed by intermolecular nucleophilic addition of two nitrone molecules, was also observed but to a lesser extent. In addition, theoretical data confirmed that the intramolecular reaction is much more favored than the intermolecular one. These nitrones were also found to efficiently trap carbon-centered radicals, but complex spectra were observed due to the presence of oxazolidine-N-oxyl derivatives.
- Choteau, Fanny,Tuccio, Beatrice,Villamena, Frederick A.,Charles, Laurence,Pucci, Bernard,Durand, Gregory
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experimental part
p. 938 - 948
(2012/03/11)
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- Synthetic libraries of tyrosine-derived bacterial metabolites
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The preparation of a collection of 131 small molecules, reminiscent of families of long chain N-acyl tyrosines, enamides and enol esters that have been isolated from heterologous expression of environmental DNA (eDNA) in Escherichia coli, is reported. The synthetic libraries of N-acyl tyrosines and their 3-keto counterparts were prepared via solid-phase routes, whereas the enamides and enol esters were synthesized in solution-phase.
- Georgiades, Savvas N.,Clardy, Jon
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supporting information; experimental part
p. 3117 - 3121
(2009/04/03)
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- IBX-mediated conversion of primary alcohols and aldehydes to N-hydroxysuccinimide esters
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Recently, the use of the hypervalent iodine reagent 1-hydroxy-1,2- benziodoxol-3(1H)-one 1-oxide (IBX) for the oxidation of primary alcohols and aldehydes to carboxylic acids was described. During the synthesis of these carboxylic acids the corresponding N-hydroxysuccinimide esters were formed as intermediate products, but their isolation as main reaction products was not successful. We report herein a simple and very efficient method to prepare these synthetically valuable active esters.
- Schulze, Agnes,Giannis, Athanassios
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p. 252 - 256
(2007/10/03)
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- Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors
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Disclosed is a novel enantiomeric synthesis cermamide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
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- Synthetic ceramide analogues as skin permeation enhancers: Structure-Activity relationships
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The study presents new information about the structure-activity relationships of the skin permeation enhancers. A series of ceramide analogues including eight different polar head groups and six different chain lengths was synthesised. The compounds were evaluated as permeation enhancers in vitro using porcine skin. The physico-chemical parameters of the tested compounds obtained by computer modelling were used to evaluate, by multiple linear regression, the enhancement ratios (ERs) of the compounds. The regression analysis suggests that the hydrogen bonding ability of the compounds is inversely related to the ER values and that the molecular size and lipophilicity must be well balanced. In the studied enhancers having the same chain length, the enhancement activity is dependent only on their permeability coefficients. This finding confirms the Warner's hypothesis that the polar head of an enhancer is responsible for the permeation and anchoring of the molecule into the stratum corneum lipids and that it does not influence the mechanism of action. For the specific action of enhancers, that is disordering of the intercellular lipid packing, the length of the hydrophobic chain(s) and not the lipophilicity is important. Furthermore, the examination of the FTIR spectra indicated that the most active substances possess the most ordered chains. The described relationships could bring more rational approaches in designing new potent enhancers for transdermal formulations.
- Vavrova, Katerina,Hrabalek, Alexandr,Dolezal, Pavel,Samalova, Lucie,Palat, Karel,Zbytovska, Jarmila,Holas, Tomas,Klimentova, Jana
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p. 5381 - 5390
(2007/10/03)
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- DI-2-PYRIDYL CARBONATE: A NEW EFFICIENT COUPLING AGENT FOR THE DIRECT ESTERIFICATION OF CARBOXYLIC ACIDS
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Reaction of carboxylic acids with equimolar amounts of di-2-pyridyl carbonate and alcohols or thiols in the presence of 4-dimethylaminopyridine as a catalyst in methylene chloride at room temperature affords the corresponding esters in high yields under mild conditions.
- Kim, Sunggak,Lee, Jae In,Ko, Young Kwan
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p. 4943 - 4946
(2007/10/02)
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- Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids.
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Several crystalline N-hydroxysuccinimide esters of short- and long-chain fatty acids have been synthesized. These compounds react with free amino acids to form preferentially N-acylamino acids. The reaction of the N-hydroxysuccinimide esters with hydroxylamine and the behavior of the N-acylamino acids on thin-layer chromatography are described.
- Lapidot,Rappoport,Wolman
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p. 142 - 145
(2007/10/08)
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