- Optimization of benzoxazinones as natural herbicide models by lipophilicity enhancement
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Benzoxazinones are plant allelochemicals well-known for their phytotoxic activity and for taking part in the defense strategies of Gramineae, Ranunculaceae, and Scrophulariceae plants. These properties, in addition to the recently optimized methodologies for their large-scale isolation and synthesis, have made some derivatives of natural products, 2,4-dihydroxy-(2H)-1,4- benzoxazin-3-(4H)-one (DIBOA) and its 7-methoxy analogue (DIMBOA), successful templates in the search for natural herbicide models. These new chemicals should be part of integrated methodologies for weed control. In ongoing research about the structure-activity relationships of benzoxazinones and the structural requirements for their phytotoxicity enhancement and after characterization of the optimal structural features, a new generation of chemicals with enhanced lipophilicity was developed. They were tested on selected standard target species and weeds in the search for the optimal aqueous solubility-lipophilicity rate for phytotoxicity. This physical parameter is known to be crucial in modern drug and agrochemical design strategies. The new compounds obtained in this way had interesting phytotoxicity profiles, empowering the phytotoxic effect of the starting benzoxazinone template in some cases. Quantitative structure-activity relationships were obtained by bioactivity-molecular parameters correlations. Because optimal lipophilicity values for phytotoxicity vary with the tested plant, these new derivatives constitute a more selective way to take advantage of benzoxazinone phytotoxic capabilities.
- Macias, Francisco A.,Marin, David,Oliveros-Bastidas, Alberto,Molinillo, Jose M. G.
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Read Online
- Enantioselective inhibition of squalene synthase by aziridine analogues of presqualene diphosphate
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(Figure Presented) Squalene synthase catalyzes the conversion of two molecules of (E,E)-farnesyl diphosphate to squalene via the cyclopropylcarbinyl intermediate, presqualene diphosphate (PSPP). Since this novel reaction constitutes the first committed step in sterol biosynthesis, there has been considerable interest and research on the stereochemistry and mechanism of the process and in the design of selective inhibitors of the enzyme. This paper reports the synthesis and characterization of five racemic and two enantiopure aziridine analogues of PSPP and the evaluation of their potencies as inhibitors of recombinant yeast squalene synthase. The key aziridine-2-methanol intermediates (6-OH, 7-OH, and 8-OH) were obtained by N-alkylations or by an N-acylation-reduction sequence of (±)-, (2R,3S)-, and (2S,3R)-2,3-aziridinofarnesol (9-OH) protected as tert-butyldimethylsilyl ethers. SN2 displacements of the corresponding methanesulfonates with pyrophosphate and methanediphosphonate anions afforded aziridine 2-methyl diphosphates and methanediphosphonates bearing N-undecyl, N-bishomogeranyl, and N-(α-methylene)bishomogeranyl substituents as mimics for the 2,6,10-trimethylundeca-2,5,9-trienyl side chain of PSPP. The 2R,3S diphosphate enantiomer bearing the N-bishomogeranyl substituent corresponding in absolute stereochemistry to PSPP proved to be the most potent inhibitor (IC50 1.17 ± 0.08 M in the presence of inorganic pyrophosphate), a value 4-fold less than that of its 2S,3R stereoisomer. The other aziridine analogues bearing the N-(α-methylene)bishomogeranyl and N-undecyl substituents, and the related methanediphosphonates, exhibited lower affinities for recombinant squalene synthase.
- Koohang, Ali,Bailey, Jessica L.,Coates, Robert M.,Erickson, Hans K.,Owen, David,Poulter, C. Dale
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Read Online
- Mild methods to assemble and pattern organic monolayers on hydrogen-terminated Si(111)
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Mild methods to assemble well-ordered organic monolayers of olefins on Si(111) using 2,2,6,6-tetramethyl-1-piperidinyloxy and to pattern these monolayers on the micrometer-size scale using soft lithography are reported. The Royal Society of Chemistry 2005.
- Arafat, Samer N.,Dutta, Samrat,Perring, Mathew,Mitchell, Michael,Kenis, Paul J. A.,Bowden, Ned B.
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Read Online
- Synthesis of Long-Chain Alkanoyl Benzenes by an Aluminum(III) Chloride-Catalyzed Destannylative Acylation Reaction
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This paper describes the facile synthesis of haloaryl compounds with long-chain alkanoyl substituents by the destannylative acylation of haloaryls bearing tri-n-butyltin (Bu3Sn) substituents. The method allows the synthesis of many important synthons for novel functional materials in a highly efficient manner. The halo-tri-n-butyltin benzenes are obtained by the lithium-halogen exchange of commercially available bis-haloarenes and the subsequent reaction with Bu3SnCl. Under typical Friedel-Crafts conditions, i.e., the presence of an acid chloride and AlCl3, the haloaryls are acylated through destannylation. The reactions proceed fast (5 min) at low temperatures and thus are compatible with aromatic halogen substituents. Furthermore, the method is applicable topara-,meta-, andortho-substitution and larger systems, as demonstrated for biphenyls. The generated tin byproducts were efficiently removed by trapping with silica/KF filtration, and most long-chain haloaryls were obtained chromatography-free. Molecular structures of several products were determined by X-ray single-crystal diffraction, and the crystal packing was investigated by mapping Hirshfeld surfaces onto individual molecules. A feasible reaction mechanism for the destannylative acylation reaction is proposed and supported through density functional theory (DFT) calculations. DFT results in combination with NMR-scale control experiments unambiguously demonstrate the importance of the tin substituent as a leaving group, which enables the acylation.
- Roemer, Max,Keaveney, Sinead T.,Proschogo, Nicholas
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p. 9007 - 9022
(2021/07/20)
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- Characterization of the molecular packing, thermotropic phase behaviour and critical micellar concentration of a homologous series of N-acyltaurines (n = 9–18). PXRD, DSC and fluorescence spectroscopic studies
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N-acyltaurines (NATs) are amides of fatty acids that can be structurally related to endocannabinoids. They show interesting physiological and pharmacological properties. We have synthesized a homologous series of NATs with saturated acyl chains (n = 9–18) and investigated their supramolecular structure and thermotropic phase transitions by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The d-spacings obtained from PXRD increase linearly with chain length with an increment of ～0.847 ? per additional CH2 moiety suggesting that NATs adopt a tilted bilayer structure with similar packing in crystal lattice. Results obtained from DSC studies indicate that the endothermic transition temperature (Tt) of NATs showed a gradually increasing trend with increasing acyl chain length. The enthalpy (ΔHt) and entropy (ΔSt) of transition show odd-even alternations with odd-chain compounds having higher values than the even-chain compounds. The critical micellar concentration (CMC) of NATs was determined in water at room temperature by fluorescence spectroscopy by monitoring the spectral changes of 8-anilinonaphthalene-1-sulfonic acid (ANS). The CMCs of NATs were found to decrease with increase in acyl chain length. The present results provide a thermodynamic and structural basis for investigating the interaction of NATs with other membrane lipids and proteins, which in turn can shed light in understanding how they function in vivo (in biological membranes).
- Arul Prakash, Sukanya,Kamlekar, Ravi Kanth
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- Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C-H Amidation
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A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C-O cleavage and an Ir-catalyzed C-H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation.
- Jung, Hoi-Yun,Chang, Sukbok,Hong, Sungwoo
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supporting information
p. 7099 - 7103
(2019/09/07)
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- PYRROLE DERIVATIVES AS ACC INHIBITORS
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Novel pyrrole derivatives of Formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Acetyl- CoA carboxylase (ACC).
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Page/Page column 48; 49
(2019/07/19)
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- Mesogenic 3,6-bis(4-hydroxyphenyl)-1,2,4,5-tetrazine alkanoate esters
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A novel series of 3,6-bis(4-hdroxyphenyl)-1,2,4,5-tetrazine alkanoate esters were synthesized and their mesogenic properties were studied using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). The impact of changing the tail-core linkage from alkyl or alkoxy to ester is profound. Compared to the alkyl or alkoxy linkages, the ester linkage reduced mesogenic properties. Short-tailed compounds are non mesogenic (4a-4e), while long-tailed compounds (4f-4r) exhibit nematic phases. Unlike the alkyl or alkoxy tail series, none of the 18 presented esters in this series exhibits a smectic phase.
- Fouad, Farid,Khabouchi, Faycal,Nielsen, Alek,Twieg, Robert
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- Synthesis, antimicrobial activity and in silico studies on thymol esters
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Derivatisation of parent structure in terpenoids often results in enhancement of biological activity of newly obtained compounds. Thymol, a naturally occurring phenol biosynthesized through the terpene pathway, is a well known biocide with strong antimicrobial attributes and diverse therapeutic activities. We have aimed our study on a single modification of phenolic functionality in thymol in order to obtain a small focused library of twenty thymyl esters, ten of which were new compounds. All compounds were involved in in vitro antimicrobial testing. Another important aspect of current study was implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties, which could be helpful by giving an additional guidance in further research.
- Lazarevi?, Jelena,Kolarevi?, Ana,Dordevi?, Aleksandra,Stojanovi?, Gordana,?melcerovi?, Andrija,Ciuffreda, Pierangela,Santaniello, Enzo
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p. 603 - 612
(2017/09/11)
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- Structure, supramolecular organization and phase behavior of N-acyl-β-alanines: Structural homologues of mammalian brain constituents N-acylglycine and N-acyl-GABA
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N-Acyl-β-alanines (NABAs) are structural homologues of N-acylglycines (NAGs) and N-acyl-γ-aminobutyric acids (NAGABAs), and achiral isomers of N-acylalanines, which are all present in mammalian brain and other tissues and modulate activity of biological receptors with various functions. In the present study, we synthesized and characterized a homologous series of NABAs bearing saturated acyl chains (n = 8-20) and investigated their supramolecular organization and thermotropic phase behavior. In differential scanning calorimetric (DSC) studies, most of the NABAs gave one or two minor transitions before the main chain-melting phase transition in the dry state as well as upon hydration with water, but gave only a single transition when hydrated with buffer (pH 7.6). Transition enthalpies (ΔHt) and entropies (ΔSt), obtained from the DSC studies showed linear dependence on the chain length in the dry state and upon hydration with buffer, whereas odd-even alteration was observed when hydrated with water. The crystal structures of N-lauroyl-β-alanine (NLBA) and N-myristoyl-β-alanine (NMBA) were solved in monoclinic system in the P21/c space group. Both NLBA and NMBA were packed in tilted bilayers with head-to-head (and tail-to-tail) arrangement with tilt angles of 33.28° and 34.42°, respectively. Strong hydrogen bonding interactions between [sbnd]COOH groups of the molecules from opposite leaflets as well as N[sbnd]H?O hydrogen bonds between the amide groups from adjacent molecules in the same leaflet as well as dispersion interactions between the acyl chains stabilize the bilayer structure. The d-spacings calculated from powder X-ray diffraction studies showed odd-even alteration with odd-chain length compounds exhibiting higher values as compared to the even-chain length ones and the tilt angles calculated from the PXRD data are higher for the even chain NABAs. These observations are relevant to developing structure-activity relationships for these amphiphiles and understand how NABAs differ from their homologues and isomers, namely NAGs, NAGABAs, and N-acylalanines.
- Sivaramakrishna,Swamy, Musti J.
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- Oil soluble molybdenum amine complex and preparation method thereof
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The invention discloses an oil soluble molybdenum amine complex and a preparation method of the oil soluble molybdenum amine complex. The method adopts long-chain saturated fatty acid as the starting material, acylchlorination reaction is carried out on the long-chain saturated fatty acid and thionyl chloride to obtain 1-chloro saturated fatty acid, then amidation reaction is carried out on the 1-chloro saturated fatty acid and diethanol amine to obtain saturated fatty acid amide, and finally complexation is carried out on the saturated fatty acid amide and a molybdenum trioxide solution so as to obtain the oil soluble molybdenum amine complex. The prepared molybdenum amine complex has good oil solubility, solves the poor oil solubility, corrosion resistance, wear resistance and friction reduction and other problems difficult to overcome in existing products, at the same time significantly reduces the adding amount of high sulfur and phosphorus components, and has enormous boosting effect on organic molybdenum series lubricating products currently under research in China, thus promoting nationalization of high-end lubricating oil and efficient utilization and high added value of molybdenum resources.
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Paragraph 0087
(2017/07/19)
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- An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues
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Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism.
- Giesbertz, Pieter,Ecker, Josef,Haag, Alexander,Spanier, Britta,Daniel, Hannelore
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p. 2029 - 2039
(2015/11/17)
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- Differential scanning calorimetric and powder X-ray diffraction studies on a homologous series of N-acyl-L-alanine esters with matched chains (n = 9-18)
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A homologous series of two chain derivatives of L-alanine, namely N-acyl L-alanine alkyl esters (NAAEs), bearing matched, saturated, acyl and alkyl chains (n= 9-18) have been synthesized. The thermotropic phase transitions and supramolecular structure of NAAEs were investigated by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results obtained from DSC studies indicate that the transition temperatures (T t), enthalpies (ΔH t) and entropies (ΔS t) exhibit odd-even alternation with compounds bearing odd acyl and alkyl chains showing higher values of T t, ΔH t and ΔS t as compared to NAAEs with even acyl and alkyl chains. However, the transition enthalpies and entropies of the odd- and even chain length series independently exhibit a linear dependence on the chain length. The d-spacings obtained from PXRD increase linearly with chain length with an increment of 1.76 ?/CH 2, suggesting that NAAEs adopt either a tilted bilayer structure or a bent structure. The present results provide a thermodynamic and structural basis for investigating the interaction of NAAEs with other membrane lipids, which in turn can shed light in understanding how they can enhance the transdermal permeability of stratum corneum.
- Sivaramakrishna,Swamy, Musti J.
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p. 1627 - 1635
(2015/12/01)
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- Structure and thermotropic phase behavior of a homologous series of n -Acylglycines: Neuroactive and antinociceptive constituents of biomembranes
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N-Acylglycines (NAGs) with different acyl chains have been found in the mammalian brain and other tissues. They exhibit significant biological and pharmacological properties and appear to play important roles in communication and signaling pathways within and between cells. In view of this, a homologous series of NAGs have been synthesized and characterized in the present study. Differential scanning calorimetric (DSC) studies show that the transition enthalpies and entropies of dry as well as hydrated NAGs exhibit a linear dependence on the acyl chain length. Most of the NAGs show a minor transition below the chain-melting phase transition, suggesting the presence of polymorphism in the solid state. Structures of N-myristoylglycine (NMG) and N-palmitoylglycine (NPG) were solved in monoclinic system with C2/c and P21 space groups, respectively. Analysis of the crystal structures show that NAGs are organized in a bilayer fashion, with head-to-head (and tail-to-tail) arrangement of molecules. The acyl chains in both structures are essentially perpendicular to the bilayer plane, which is consistent with a lack of odd-even alternation in the thermodynamic properties. The bilayer is stabilized by strong hydrogen bonding interactions between COOH groups of the molecules from opposite leaflets as well as N-H···O hydrogen bonds between the amide groups of adjacent molecules in the same leaflet and dispersion interactions among the acyl chains. Powder X-ray diffraction data show that the d-spacings for the NAGs with different acyl chains (n = 8-20) exhibit a linear dependence on the chain length, suggesting that all the NAGs investigated here adopt a similar packing arrangement in the crystal lattice. These observations are relevant for understanding the role of N-acylglycines in biological membranes.
- Reddy, S. Thirupathi,Krovi, Krishna Prasad,Swamy, Musti J.
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p. 4944 - 4954
(2014/12/10)
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- Anti-influenza active and low toxic N-phenyl-substituted β-amidoamidines structurally related to natural antibiotic amidinomycin
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A set of racemic N-phenyl-substituted β-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). In the final step of the synthetic route, an uncommon monoacylation of β-aminoamidine 8 at the less reactive β-phenylamino-group took place. To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to β-phenylamino-group was suggested. All three β-amidoamidines 4d-f bearing long linear aliphatic chain (from n-C8H17 to n-C12H25) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity. The in vitro antiviral potency of 4d,e is 6-20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index. The non-toxic in vivo compounds 4d-f showed a beneficial protective effect in influenza A (H3N2) infected mice.
- Korshin, Edward E.,Zakharova, Lyubov G.,Levin, Yakov A.,Shulaeva, Marina P.,Pozdeev, Oskar K.
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supporting information
p. 2357 - 2361
(2013/05/09)
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- Carbohydrate liquid crystals: Synthesis and characterisation of the methyl-6-O-(n-acyl)-α-D-glucopyranosides
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Seven members of the methyl-6-O-(n-acyl)-α-d-glucopyranosides have been synthesised and their transitional properties determined. The undecanoyl and octadecanoyl members do not exhibit liquid crystallinity while the members having chain lengths between dodecanoyl and hexadecanoyl exhibit a monotropic smectic A phase. Variable temperature infrared spectroscopy reveals that the hydrogen bonding within the system shows a marked change at the melting point but apparently no change at the smectic A-isotropic transition. This observation is interpreted in terms of Goodby's model for the smectic A phase in which the carbohydrate moieties are located at the centre of the smectic bilayer and assuming that hydrogen bonded aggregates persist into the isotropic phase. Within this framework, the unusually low values of the entropy change associated with the smectic A-isotropic transition may also be accounted for.
- Cook, Andrew G.,Wardell, James L.,Imrie, Corrie T.
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scheme or table
p. 118 - 124
(2012/03/10)
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- Synthesis, calorimetric studies, and crystal structures of N, O-diacylethanolamines with matched chains
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Recent studies show that N-, O -diacylethanolamines (DAEs) can be derived by the O -acylation of N-acylethanolamines (NAEs) under physiological conditions. Because the content of NAEs in a variety of organisms increases in response to stress, it is likely that DAEs may also be present in biomembranes. In view of this, a homologous series of DAEs with matched acyl chains (n = 10-20) have been synthesized and characterized. Transition enthalpies and entropies obtained from differential scanning calorimetry show that dry DAEs with even and odd acyl chains independently exhibit linear dependence on the chainlength. Linear least-squares analyses yielded incremental values contributed by each methylene group to the transition enthalpy and entropy and the corresponding end contributions. N-, O-Didecanoylethanolamine (DDEA), N-, O-dilauroylethanolamine (DLEA), and N-, O-dimyristoylethanolamine (DMEA) crystallized in the orthorhombic space group Pbc21 with four symmetry-related molecules in the unit cell. Single-crystal X-ray diffraction studies show that DDEA, DLEA, and DMEA are isostructural and adopt an L-shaped structure with the N-acyl chain and the central ethanolamine moiety being essentially identical to the structure of N-acylethanolamines, whereas the O-acyl chain is linear with all-trans conformation. In all three DAEs, the lipid molecules are organized in a bilayer fashion wherein the N-acyl and O-acyl chains from adjacent layers oppose each other. Copyright
- Kamlekar, Ravi Kanth,Tarafdar, Pradip K.,Swamy, Musti J.
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body text
p. 42 - 52
(2010/11/04)
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- Application of hansch's model to capsaicinoids and capsinoids: A study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids
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We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity. A total of 14 capsaicinoids of increasing lateral chain lengths, from 2 to 16 carbon atoms, were synthesized. In addition, 14 capsinoids with identical lateral chains, as well as capsiate and dihydrocapsiate, have been synthesized, and a new method for the synthesis of these compounds has been developed. The yields range from 48.35 to 98.98%. It has been found that the synthetic capsaicinoids and capsinoids present a lipophilia similar to those of the natural compounds and present similar biological activity. The bioactivity of the synthetic capsaicinoids and capsinoids decreases proportionally to the degree of difference in lipophilia (higher or lower) compared to the natural compounds. Biological activity was determined using the etiolated wheat (Triticum aestlvum L.) coleoptiles bioassay and by comparing results of the synthesis with those presented by their counterpart natural compounds. The bioactivities found correlated directly to the lipophilic properties of the synthesized compounds.
- Barbero, Gerardo F.,Molinillo, Jose M. G.,Varela, Rosa M.,Palma, Miguel,MacIas, Francisco A.,Barroso, Carmelo G.
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experimental part
p. 3342 - 3349
(2011/07/30)
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- Effect of chain ends on the structure of aramid oligomers
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Synthesis, X-ray diffraction, and Fourier transform, infrared spectroscopy of aliphatic-aromatic aramid oligomers are reported with the aim of shedding light on the effect of end-chain substituent on the morphology and structure of poly(para-phenylene terephthalamide) or PPTA. Three types of X-ray powder diffraction patterns were observed: one similar to that of PPTA form I, one similar to that of PPTA form II, and an additional form never reported. Some compounds, differing by their internal distribution of amide-aromatic rings, adopt two different crystal structures, whereas compounds having the same internal amide-aromatic arrangements, but differing by the nature of the end-groups, can adopt the same crystal structure. This clearly shows that both factors influence the packing adopted by the chains. Single-crystal structures of two polymorphs of a nitro-terminated model compound were resolved; both forms incorporate dimethyl formamide, and both show completely different packing. Infrared amide I and II band positions of most studied compounds match those observed for PPTA forms I or II, indicating that they exhibit planar hydrogen bonded sheets of molecules.
- Mehenni, Hakim,Guillou, Helene,Tessier, Christian,Brisson, Josee
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- Synthesis and transdermal permeation-enhancing activity of carbonate and carbamate analogs of Transkarbam 12
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Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbonyl)pentylcarbamate, T12) is a highly effective skin permeation enhancer. In this study, ester groups in the molecule of T12 were replaced by carbonate and carbamate ones, respectively. The in vitro permeation-enhancing activities were evaluated using porcine skin and compared with those of T12 and previously prepared series of amide, ketone, and alkyl analogs. According to the activities and behavior of the compounds in donor samples, ester group is essential for the activity of T12; its replacement not only decreases the enhancing potency, but is likely to change the mechanism of action.
- Holas, Tomas,Vavrova, Katerina,Sima, Martin,Klimentova, Jana,Hrabalek, Alexandr
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p. 7671 - 7680
(2007/10/03)
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- Lipophilic pyrylium salts in the synthesis of efficient pyridinium-based cationic lipids, gemini surfactants, and lipophilic oligomers for gene delivery
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Several new classes of pyridinium cationic lipids were synthesized and tested as gene delivery agents. They were obtained through a procedure that generates simultaneously the heterocyclic ring and the positively charged nitrogen atom, using lipophilic pyrylium salts as key intermediates that react with primary amines, yielding pyridinium salts. The choice of the appropriately substituted primary amine, diamine or polyamine, allows the design of the shape of the final lipids, gemini surfactants, or lipophilic polycations. We report also a comprehensive structure-activity relationship study that identified the most efficient structural variables at the levels of the hydrophobic anchor, linker, and counterion for these classes of pyridinium cationic lipids. This study was also aimed at finding the best liposomal formulation for the new transfection agents.
- Ilies, Marc Antoniu,Seitz, William A.,Johnson, Betty H.,Ezell, Edward L.,Miller, Aaron L.,Thompson, E. Brad,Balaban, Alexandru T.
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p. 3872 - 3887
(2007/10/03)
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- Discovery of a potent, selective, and efficacious class of reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics
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Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routine implementation of a proteomics-wide selectivity screen against the serine hydrolase superfamily ensuring selectivity for FAAH coupled with systematic in vivo examinations of candidate inhibitors.
- Boger, Dale L.,Miyauchi, Hiroshi,Du, Wu,Hardouin, Christophe,Fecik, Robert A.,Cheng, Heng,Hwang, Inkyu,Hedrick, Michael P.,Leung, Donmienne,Acevedo, Orlando,Guimar?es, Cristiano R. W.,Jorgensen, William L.,Cravatt, Benjamin F.
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p. 1849 - 1856
(2007/10/03)
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- Synthesis of N-aryl-N′-undecanoyl thiourea derivatives
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The reaction of undecanoyl isothiocyanate with certain primary amines leads to the formation of the corresponding N-aryl-N′-undecanoylthiocarbamides. The above-mentioned isothiocyanates were obtained in situ by reaction of undecanoyl chloride with KSCN. The new compounds were characterised by spectroscopic methods data (IR, 1H-NMR and 13C-NMR).
- Loloiu, George,Loloiu, Teodora,Bǎdicu, Niculina,Gavriliu, Daniela,Maior, Ovidiu
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p. 899 - 903
(2007/10/03)
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- Lithium/DTBB-induced reduction of N-alkoxyamides and acyl azides
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A series of N-alkoxyamides and N-methoxy-N-methylamides (Weinreb amides) have been subjected to dealkoxylation by reductive cleavage of the N-O bond with lithium powder and a catalytic amount of DTBB (10 mol%) at room temperature, leading to the corresponding amides. When the reaction is performed under reflux conditions, the corresponding alkanes, resulting from a formal deaminocarbonylation process, are obtained. This methodology applied to acyl azides furnished the corresponding primary amides.
- Yus, Miguel,Radivoy, Gabriel,Alonso, Francisco
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p. 914 - 918
(2007/10/03)
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- Heterosupramolecular Chemistry: Synthetic Strategies for the Covalent and Noncovalent Assembly and Organization of Nanocrystals and Molecules
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Described are the preparation of nanocrystals and the synthesis of molecules that may be covalently or noncovalently assembled in solution to yield heterosupermolecules possessing a well-defined heterosupramolecular function. Also described are preparative and synthetic methods that yield organized assemblies of heterosupermolecules possessing an addressable heterosupramolecular function. Finally, the development of these synthetic strategies to permit the covalent and noncovalent assembly and organization of a wide range of condensed phase and molecular components is outlined.
- Nagarajo Rao,Fitzmaurice, Donald
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p. 902 - 915
(2007/10/03)
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- Insecticidal 5-substituted-2,4-diaminopyrimidine derivatives
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An insecticidal composition comprising, in admixture with an agriculturally acceptable carrier, an insecticidally effective amount of a compound of the formula: STR1 wherein R, R1, R2, R3, R7, R8, m, n, and p are as defined herein, and agriculturally acceptable salts thereof, and methods of using the same.
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- Generation of Acyl Radicals from 2-Naphthyl Thioesters
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A series of S-2-naphthyl thioesters were synthesized from the corresponding carboxylic acids or acid chlorides.Irradiation of these thioesters in the presence of a hydrogen source (i.e., 1,4-cyclohexadiene) generated the corresponding aldehydes.In this fashion, primary, secondary, tertiary, and aryl carboxylic acids were converted to the aldehydes in high yields.Intramolecular radical cyclization reactions support the hypothesis that the reaction proceeds via the formation of acyl radicals.The formation of aldehydes was not perturbed by possible Norrish Type II reactions.
- Penn, John H.,Liu, Fang
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p. 2608 - 2612
(2007/10/02)
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- Synthesis and preliminary evaluation of perfluoroalkylacyl carnitines as surfactants for biomedical use
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A series of acyl carnitines, 4 of which bearing a terminal perfluoroalkyl fragment, was obtained from carnitine in one step in a high grade of purity in yields ranging from 44-81percent.The F-alkyl derivatives display high solubilities in water, strong surface activity and a significant emulsifying power towards fluorocarbons in water.In spite of their strong surface activity, all of the biocompatibility tests performed (in vitro toxicity on Namalva cells cultures, hemolysis on human red blood cells, and iv injections in mice) indicate a significantly better biologicaltolerance than their hydrocarbon analogs, provided the F-alkyl moiety is larger than the alkyl moiety in the hydrophobic tail. fluorinated acyl carnitines / surfactants / emulsifiers / synthesis / biological acceptance / hemolysis / fluorocarbon emulsions
- Nivet, JB,Blanc, M Le,Riess, JG
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p. 953 - 960
(2007/10/02)
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- FERROCENE DERIVATIVES, SURFACTANTS CONTAINING SAME, AND PROCESS FOR PRODUCING THIN ORGANIC FILM
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Novel ferrocene derivatives represented by general formula (I) or general formula (II) (wher-ein symbols are as defined in the specification) are excellent as surfactants. A thin organic film of a hydrophobic organic substance may efficiently be produced by an electrochemical process using the novel ferrocene derivative or other ferrocene de-rivative as a micelle-forming agent (surfactant). AbstractNovel ferrocene derivatives represented by the general formula: or the general formula: (wherein all the symbols are as described in the specification) are excellent as surfactants. By application of an electrochemical method using the novel ferrocene derivatives or other ferrocene derivatives as micelle forming agents (surfactants), an organic thin film of a hydrophobic organic substance can be efficiently produced.
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- INTERPRETING SUBSTITUENT EFFECTS ON THE CRYSTAL PACKING OF LONG-CHAIN DIACYL PEROXXIDES. THE CRYSTAL STRUCTURES OF DI(11-BROMOUNDECANOYL) PEROXIDE AND DI(UNDECANOYL) PEROXIDE
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Although crystals of di(11-bromoundecanoyl) peroxide and di(undecanoyl) peroxide have different space groups (P43212 and C2221), the molecules pack in almost identical layers.They differ only in the nature of stacking across interfaces involving the terminal groups.Because the 90 deg twist about the O-O bond locks neighboring molecules together within the layer, each peroxide shows a single solid phase from 5K to the melting point.Analysis of the stacking pattern in terms of the six possible orientational relationships suggests special stability for an L-shaped motif of C-Br...Br-C.Other substituents create different stackings of the same layer structure to give three crystal classes and five space groups among 14 compounds.Unsymmetrical peroxides are useful both for forcing a variety of substituted chains (particularly odd-even homologues) to pack with identical layer structures, and for controlling the stacking pattern.Because structural differences are localized in the vicinity of the substituents, this series of "substitutional polytypes" will allow systematic investigation of substituent effects on the physical and chemical properties of solids.
- McBride, J. Michael,Bertman, Steven B.,Cioffi, Donna Z.,Segmuller, Brigitte E.,Weber, Bruce A.
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- ACETYLENIC FRAGMENTATION OF ACYL DERIVATIVES OF THE FISCHER BASE
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Indolenium salts, which readily undergo cleavage in aqueous alkali to give a monosubstituted acetylene and 1,3,3-trimethyl-2-oxindole, are formed when acyl derivatives of the Fischer base are heated with phosphorus oxychloride.Various aryl- and hetarylacetylenes can be conveniently obtained by this method.
- Prizhiyalgovskaya, N. M.,Kon'kov, L. I.,Tarshits, D. L.,Salmina, S. V.,Segizova, N. T.,Suvorov, N. N.
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p. 751 - 754
(2007/10/02)
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- 2-Acyl-3-substituted cyclopentan-1-ones and process for their preparation
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1,3-Dicarbonyl compounds useful as medicines, agricultural chemicals, perfumes, and their intermediates are prepared by reacting a specific α,β-unsaturated carbonyl compound with a specific organic copper lithium compound in the presence of an aprotic inert organic solvent, and then reacting the reaction product with an organic carboxylic acid halide or anhydride. In particular, novel 2-acyl-3-substituted cyclopentan-1-ones and 2-acyl-3-substituted cyclohexan-1-ones having important physiological activities are provided.
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