- Pachychalines A-C: Novel 3-alkylpyridinium salts from the marine sponge Pachychalina sp.
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Three 3-alkylpyridinium salts, pachychalines A (1), B (2) and C (3), were isolated from the Caribbean marine sponge Pachychalina sp. (order Haplosclerida). They are the first examples of 3-(aminoalkyl)pyridinium salts. Their chemical structures were elucidated by NMR spectroscopy and detailed ESI HRMS-MS analysis. The total synthesis of 1 allowed the confirmation of the unusual C-C connection between both pyridinium moieties. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Laville, Remi,Thomas, Olivier P.,Berrue, Fabrice,Reyes, Fernando,Amade, Philippe
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Read Online
- Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,β-Unsaturated Carbonyl Compounds
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The long-range deconjugative isomerization of a broad range of α,β-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and β-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,β-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,β-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization.
- Lin, Luqing,Romano, Ciro,Mazet, Clément
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p. 10344 - 10350
(2016/08/31)
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- Scalable Synthesis of Human Ultralong Chain Ceramides
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Ceramides with ultralong chains (≥30 carbons), also known as acylceramides, play a critical role in the survival of mammals on dry land. An efficient and scalable synthesis of four major classes of ultralong human skin ceramides is reported. The key approach involves the use of a succinimidyl ester that acts as a protective group, helps overcome the extremely low solubility, and simultaneously activates the fatty acid for its clean and high-yielding attachment to a sphingoid base.
- Opálka, Luká?,Ková?ik, Andrej,Sochorová, Michaela,Roh, Jaroslav,Kune?, Ji?í,Len?o, Juraj,Vávrová, Kate?ina
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supporting information
p. 5456 - 5459
(2015/11/18)
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- Conformationally-locked N -glycosides: Exploiting long-range non-glycone interactions in the design of pharmacological chaperones for Gaucher disease
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Pyranoid-type glycomimetics having a cis-1,2-fused glucopyranose-2-alkylsulfanyl-1,3-oxazoline (Glc-PSO) structure exhibit an unprecedented specificity as inhibitors of mammalian β-glucosidase. Notably, their inhibitory potency against human β-glucocerebrosidase (GCase) was found to be strongly dependent on the nature of aglycone-type moieties attached at the sulfur atom. In the particular case of υ-substituted hexadecyl chains, an amazing influence of the terminal group was observed. A comparative study on a series of Glc-PSO derivatives suggests that hydrogen bond acceptor functionalities, e.g. fluoro or methyloxycarbonyl, significantly stabilize the Glc-PSO:GCase complex. The S-(16-fluorohexadecyl)-PSO glycomimetic turned out to be a more potent GCase competitive inhibitor than ambroxol, a non glycomimetic drug currently in pilot trials as a pharmacological chaperone for Gaucher disease. Moreover, the inhibition constant increased by one order of magnitude when shifting from neutral (pH 7) to acidic (pH 5) media, a favorable characteristic for a chaperone candidate. Indeed, the fluoro-PSO derivative also proved superior to ambroxol in mutant GCase activity enhancement assays in N370S/N370S Gaucher fibroblasts. The results presented here represent a proof of concept of the potential of exploiting long-range non-glycone interactions for the optimization of glycosidase inhibitors with chaperone activity.
- Castilla, Javier,Rísquez, Rocío,Higaki, Katsumi,Nanba, Eiji,Ohno, Kousaku,Suzuki, Yoshiyuki,Díaz, Yolanda,Ortiz Mellet, Carmen,García Fernández, José M.,Castillón, Sergio
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supporting information
p. 258 - 266
(2015/01/08)
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- Synthesis of new ligands for targeting the S1P1 receptor
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Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [18F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases.
- Schilson, Stefanie S.,Keul, Petra,Shaikh, Rizwan S.,Sch?fers, Michael,Levkau, Bodo,Haufe, Günter
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p. 1011 - 1026
(2015/03/04)
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- NEW LIGANDS FOR TARGETING OF S1P RECEPTORS FOR IN VIVO IMAGING AND TREATMENT OF DISEASES
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The present invention relates to novel compounds of formulae (I) and (II) which are useful in the prevention, treatment and diagnosis, in vivo diagnosis of diseases or disorders related to S1P receptors, in particular, in diseases which are connected to the regulatory function of sphingosine-1-phosphate (S1P) and its analogues, such as inflammation, pain, autoimmune diseases and cardiovascular diseases.
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- ANTIMICROBIAL MONOMERS FOR USE IN DENTAL POLYMERS
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Antimicrobial compounds are provided that are polymerizable. The compounds include monomers with antimicrobial properties. The compounds have cross-linking properties and are hydrolytically stable. The compounds may be utilized in dental and/or medical applications, including dental composites, dentures, bonding agents, sealants, resins and medical devices.
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Paragraph 0054-0055
(2014/10/29)
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- BASELESS NUCLEOTIDE ANALOGUES AND USES THEREOF
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A method of detecting a target nucleic acid.
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Paragraph 0126; 0127
(2014/05/07)
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- NEW LIGANDS FOR TARGETING OF S1P RECEPTORS FOR IN VIVO IMAGING AND TREATMENT OF DISEASES
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The present invention relates to novel compounds of formulae (I) and (II) which are useful in the prevention, treatment and diagnosis, in vivo diagnosis of diseases or disorders related to S1P receptors, in particular, in diseases which are connected to the regulatory function of sphingosine-1-phosphate (S1P) and its analogues, such as inflammation, pain, autoimmune diseases and cardiovascular diseases.
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- Maltoside and Phosphocholine Derivatives, Uses thereof and Methods of Preparing Artificial Lipid Structures Thereof
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Disclosed are saccharide and phosphocholine derivatives. The derivatives include azide and alkyne derivatives which form one end of a variable length carbon chain. The opposite end of the variable length carbon chain is covalently linked to the saccharide or phosphocholine. The saccharide may be, for instance, a maltoside. The alkyne and azide derivatives of the saccharides and phosphocholine may be reacted together to form amphiphilic molecules useful in cellular membrane studies and applications. By adjusting the length of the carbon chain, the biochemical and biophysical properties of the resultant 1,4-disubstituted 1,2,3-triazole compounds may be custom tailored for the intended application. Resultant molecules may form micelles, bicelle, lipid bilayers and other like structures useful in the isolation and purification of membrane bound or membrane associated proteins and biochemical components. The saccharides and phosphocholine molecules may be alternatively substituted as desired to provide additional flexibility in designing the desired end product.
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Paragraph 0053
(2013/04/24)
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- Conformationally-locked N -glycosides with selective β-glucosidase inhibitory activity: Identification of a new non-iminosugar-type pharmacological chaperone for gaucher disease
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A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)2 as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian β-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(ω-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal β-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.
- Castilla, Javier,Rísquez, Rocío,Cruz, Deysi,Higaki, Katsumi,Nanba, Eiji,Ohno, Kousaku,Suzuki, Yoshiyuki,Díaz, Yolanda,Mellet, Carmen Ortiz,Fernández, José M. García,Castillón, Sergio
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supporting information; experimental part
p. 6857 - 6865
(2012/09/22)
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- Hydroxylated Long-Chain Resveratrol Derivatives Useful as Neurotrophic Agents
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The present invention relates to a compound of general formula (I) below in which R1, R2 and R3 represent, independently of one another, a hydrogen atom or a C1-C6 alkyl group or a (C1-C6 alkyl)carbonyl group, R4, R5, R6 and R7 represent a hydrogen or a C1-C6 alkyl group, a C1-C6 alkoxy group or a (C1-C6 alkyl)carbonyloxy group, and n is an integer between 8 and 20, or its pharmaceutically acceptable addition salts, isomers, enantiomers and diastereoisomers, and also mixtures thereof. The invention also relates to a pharmaceutical composition comprising the compound and to the use thereof as a neurotrophic agent.
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Page/Page column 9
(2010/03/31)
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- First syntheses of model long-chain trichloro[ω-(trimethylsilyl)alkynyl]silanes suitable for self-assembled monolayers on silicon surfaces
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The preparation of the title compounds involves the introduction of the required Me3SiC{triple bond, long}C and trichlorosilyl groups at the termini of the alkyl chain via derivatization of easily accessible and inexpensive materials/reagents. Trichloro[ω-(trimethylsilyl)alkynyl]silanes are useful for the linkage to a hydroxylated silicon surface for multilayer formation and for further chemical modification of the tail group of the monolayer.
- Banaszak, Estelle,Xu, Li-Wen,Bardeau, Jean-Fran?ois,Castanet, Anne-Sophie,Mortier, Jacques
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body text
p. 3961 - 3966
(2009/09/30)
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- General synthesis and aggregation behaviour of a series of single-chain 1,ω-Bis(phosphocholines)
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The synthesis and physicochemical characterisation of a series of polymethylene-1,ω-bis(phosphocholines) with even-numbered chain lengths between 22 and 32 carbon atoms is described. Two new synthetic strategies for the preparation of long-chain 1,ω-diols as hydrocarbon building blocks are presented. The temperature-dependent self-assembly of the single-chain bolaamphiphiles was investigated by cryo transmission electron microscopy (cryo-TEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR).
- Drescher, Simon,Meister, Annette,Blume, Alfred,Karlsson, Goeran,Almgren, Mats,Dobner, Bodo
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p. 5300 - 5307
(2008/02/11)
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- HYDROQUINONE LONG-CHAIN DERIVATIVE AND/OR PHENOXY LONG-CHAIN DERIVATIVE, AND PHARMACEUTICAL PREPARATION COMPRISING THE SAME
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The present invention provides compounds represented by formula (1) shown below: (wherein R1, R2, R3, R4, and R5 are each individually selected from among a hydrogen atom, methyl group, acetyl group, hydroxyl group, and alkoxy group; and X represents an alkylene group or alkenylene group); and compounds represented by formula (2) shown below: (wherein R6, R7, R8, R9, and R10 are each individually selected from among a hydrogen atom, alkyl group, acetyl group, hydroxyl group, and alkoxy group; A represents an oxygen atom or NH, and m is 0 or 1; and Y represents an alkylene group or alkenylene group, and Z represents a hydrogen atom or hydroxyl group).The compounds of the present invention are useful for preventing or treating brain dysfunctions, motor dysfunctions, or urinary dysfunctions caused by the degeneration and/or loss of the central nervous system or peripheral nervous system cells.The present invention provides compounds represented by formula (1) shown below: (wherein R 1 , R 2 , R 3 , R 4 , and R 5 are each individually selected from among a hydrogen atom, methyl group, acetyl group, hydroxyl group, and alkoxy group; and X represents an alkylene group or alkenylene group); and compounds represented by formula (2) shown below: (wherein R 6 , R 7 , R 8 , R 9 , and R 10 are each individually selected from among a hydrogen atom, alkyl group, acetyl group, hydroxyl group, and alkoxy group; A represents an oxygen atom or NH, and m is 0 or 1; and Y represents an alkylene group or alkenylene group, and Z represents a hydrogen atom or hydroxyl group). The compounds of the present invention are useful for preventing or treating brain dysfunctions, motor dysfunctions, or urinary dysfunctions caused by the degeneration and/or loss of the central nervous system or peripheral nervous system cells.
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Page/Page column 16
(2008/06/13)
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- Solid-phase synthesis of quinol fatty alcohols, design of N/O-substituted quinol fatty alcohols and comparative activities on axonal growth
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Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n = 14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation allows good retention of the biological activity, N-alkylation abolishes it nonetheless. A solid-phase-supported synthesis of Q2FA15 allowing the conception of new hybrid compounds is also described.
- Hanbali, Mazen,Bagnard, Dominique,Luu, Bang
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p. 3917 - 3920
(2007/10/03)
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- Quinol fatty alcohols as promoters of axonal growth
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The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n = 15), shows the most potent promotion of axonal growth in the presence of both permissive and non-permissive naturally occurring substrates such as Sema3A and myelin proteins.
- Hanbali, Mazen,Vela-Ruiz, Marta,Bagnard, Dominique,Luu, Bang
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p. 2637 - 2640
(2007/10/03)
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- Self-assembled monolayers of nitrile-functionalized alkanethiols on gold and silver substrates
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Self-assembled monolayers (SAMs) formed from nitrile-functionalized alkanethiols (AT), NC(CH2)16SH (NC-Cl6), on (111) gold and silver substrates were characterized by X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and contact angle measurements. The average chain tilt angles in NC-C16/Ag and NC-C16/Au were estimated to be 29.5° ± 5° and 42.5° ± 5° from the surface normal, respectively, while the data suggest lower ordering for NC-C16/Au. The -C≡N bonds were found to be predominantly oriented in the surface plane with a tilt angle of 65° ± 7° for both NC-C16/Au and NC-C16/ Ag. Comparison with previous data on CH3-terminated SAMs reveals that substitution of weakly interacting CH3 groups by the CN entities results in an increase in the average tilt angles of the alkyl chains by ~7.5° and ~17.5° in AT/Au and AT/Ag, respectively. A strong electrostatic interaction between the polar nitrile groups is assumed to underlie the structural behavior by controlling a balance between the headgroupsubstrate and interchain interactions. The near-parallel orientation of the nitrile groups to the surface in both of these SAMs can be explained on the basis of minimization of the unfavorable CN - CN dipole - dipole interactions.
- Frey,Shaporenko,Zharnikov,Harder,Allara
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p. 7716 - 7725
(2007/10/03)
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- Electronic methods for the detection of analytes utilizing monolayers
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The present invention relates to the use of self-assembled monolayers with mixtures of conductive oligomers and insulators to detect target analytes.
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- Bond insertion, complexation, and penetration pathways of vapor-deposited aluminum atoms with HO- and CH3O-terminated organic monolayers
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The interaction of vapor-deposited Al atoms with self-assembled monolayers (SAMs) of HS-(CH2)16-X (X = -OH and -OCH3) chemisorbed at polycrystalline Au{111} surfaces was studied using time-of-flight secondary-ion mass spectrometry, X-ray photoelectron spectroscopy, and infrared reflectance spectroscopy. Whereas quantum chemical theory calculations show that Al insertion into the C-C, C-H, C-O, and O-H bonds is favorable energetically, it is observed that deposited Al inserts only with the OH SAM to form an -O-Al-H product. This reaction appears to cease prior to complete -OH consumption, and is followed by formation of a few overlayers of a nonmetallic type of phase and finally deposition of a metallic film. In contrast, for the OCH3 SAM, the deposited Al atoms partition along two parallel paths: nucleation and growth of an overlayer metal film, and penetration through the OCH3 SAM to the monolayer/Au interface region. By considering a previous observation that a CH3 terminal group favors penetration as the dominant initial process, and using theory calculations of Al-molecule interaction energies, we suggest that the competition between the penetration and overlayer film nucleation channels is regulated by small differences in the Al-SAM terminal group interaction energies. These results demonstrate the highly subtle effects of surface structure and composition on the nucleation and growth of metal films on organic surfaces and point to a new perspective on organometallic and metal-solvent interactions.
- Fisher, Gregory L.,Walker, Amy V.,Hooper, Andrew E.,Tighe, Timothy B.,Bahnck, Kevin B.,Skriba, Hope T.,Reinard, Michael D.,Haynie, Brendan C.,Opila, Robert L.,Winograd, Nicholas,Allara, David L.
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p. 5528 - 5541
(2007/10/03)
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- Methods of attaching conductive oligomers to electrodes
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The invention relates to nucleic acids covalently coupled to electrodes via conductive oligomers. More particularly, the invention is directed to the site-selective modification of nucleic acids with electron transfer moieties and electrodes to produce a new class of biomaterials, and to methods of making and using them.
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- Effect of cyclohexenonic long chain fatty alcohols on neurite outgrowth. Study on structure-activity relationship
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Four series of long chain fatty alcohols bearing a cyclohexenone moiety in addition to a ω-alkanol side chain were synthesized using 'Umpolung' reactivity strategy. Their effect on neurite outgrowth was evaluated by means of fetal rat neurons in culture. The length of the ω-hydroxy side chain is a crucial factor for biological activity.
- Girlanda-Junges, Celine,Keyling-Bilger, Florence,Schmitt, Gaby,Luu, Bang
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p. 7735 - 7748
(2007/10/03)
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- Synthesis of elenic acid, an inhibitor of topoisomerase II from the sponge Plakinastrella sp.
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(R)-(-)-Elenic acid 1, an inhibitor of topoisomerase II isolated from the marine sponge Plakinastrella sp., has been synthesized starting from hexadecane-1,16-diol 2 and methyl (S)3-hydroxy-2-methylpropanoate 6.
- Takanashi, Shin-Ichi,Takagi, Masanori,Takikawa, Hirosato,Mori, Kenji
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p. 1603 - 1606
(2007/10/03)
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- Multiple Electron Tunneling Paths across Self-Assembled Monolayers of Alkanethiols with Attached Ruthenium(II/III) Redox Centers
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Alkanethiol monolayers with pendant redox centers are deposited on gold electrodes by selfassembly.The monolayers are composed of both an electroactive thiol, HS(CH2)nC(O)NHCH2pyRu(NH3)5(2+/3+), with 10-15 methylene groups, and a diluent thiol, HS(CH2)mCOOH, also with 10-15 methylene groups.The monolayers are classified as "matched" (n = m), "exposed" ( n = 15, m = 10-14), and "buried" (n = 10, m = 11-15) according to the relative position of the redox center.Cyclic voltammograms in aqueous Na2SO4 indicate that the monolayers are close-packed with the redox centers residing in the aqueous phase in all but the most buried cases.Measurements of electron transfer kinetics by several methods (cyclic voltammetry, ac impedance spectroscopy, chronoamperometry) yield an internally consistent set of kinetic parameters, the standard rate constant ko, and the reorganization energy λ of the redox centers.The reorganization energies are in good agreement with the theoretically predicted value of 1.0 eV for the pyRu(NH3)5 redox centers.Plots of ln(ko) vs m are linear in all three cases.The slopes of the linear regression fit provide tunneling parameters (β, where ko ca. e-βm) of 0.97 +/- 0.03 (matched cases), 0,83 +/- 0.03 (exposed cases) and 0.16 +/- 0.02 (buried cases) per methylene.This pattern of β's is interpreted in terms of electronic coupling between the redox center and the electrode via both the redox thiol and the proximate diluent thiols, with the coupling via the diluent thiols dominating in the exposed cases.
- Finklea, Harry O.,Liu, Luna,Ravenscroft Melissa S.,Punturi, Sesto
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p. 18852 - 18858
(2007/10/03)
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- Total Synthesis of Naturally Occurring Mycolic Acids. (E)- and (Z)-threo-2-Docosyl-3-hydroxytetracont-21-enoate
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The ethyl esters of (E)- and (Z)-2-docosyl-3-hydroxytetracont-21-enoate (4a and 4b, respectively) have been prepared by a route involving alkylation of the dianion of ethyl 2-docosyl-3-oxobutyrate (2) with either (E)-1-iodo-17-hexatriacontene (14c) or (Z)-1-iodo-17-hexatriacontene (13c) and subsequent borohydride reduction of the intermediate β-keto esters (3a and 3b, respectively).Resolution of the 3:2 mixture of erythro and threo diastereomers of 4a and 4b was accomplished by high-performance liquid chromatography, employing phenacyl ester derivatives.The 1H NMR spectra of phenacyl (E)-threo-2-docosyl-3-hydroxytetracont-21-enoate (6a) and phenacyl (Z)-threo-2-docosyl-3-hydroxytetracont-21-enoate (6b) were identical with the spectra previously reported for the phenacyl esters of the naturally occurring monoalkene mycolic acids from Mycobacterium smegmatis (see ref 10).An examination of the phenacyl ester of the epoxide derivative of the naturally occurring mycolic acid by 1H NMR spectroscopy established that it was a 93:7 mixture of the Z and E isomers, respectively, of phenacyl threo-2-docosyl-3-hydroxytetracont-21-enoate.
- Huang, Harry C.,Rehmann, Jill K.,Gray, Gary R.
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p. 4018 - 4023
(2007/10/02)
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