- A Facile and Efficient Method for the Synthesis of Labeled and Unlabeled Very Long Chain Polyunsaturated Fatty Acids
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Several methods are available for elongation of fatty acid acyl chains. The present paper describes adaptation to the fatty acid field of a previously published protocol for manganese-based Wurtz type coupling of alkyl bromides. 22-Bromo-3(Z),6(Z),9(Z),12(Z),15(Z),18(Z)-docosahexaene, easily prepared from 4(Z),7(Z),10(Z),13(Z),16(Z),19(Z)-docosahexaenoic acid, was coupled to homologous ω-bromoesters by stirring for 4 hours at 40°C in the presence of manganese powder, a nickel catalyst and terpyridine. This afforded in yields of 70–75% a series of ω3-hexaenoates of chain lengths of 32–40 carbons. The corresponding fatty acids of >98% purity were obtained following saponification and final purification. By using methyl [2,2,3,3,4,4-2H6]10-bromodecanoate as coupling partner it was possible to prepare a very long chain fatty acid in isotopically labeled form, i.e., [2,2,3,3,4,4-2H6]14(Z),17(Z),20(Z),23(Z),26(Z),29(Z)-dotriacontahexaenoic acid. Also prepared were the monounsaturated long chain fatty acids 15(Z)-octadecenoic acid and 15(Z)-tetracosenoic acid. Very long chain fatty acids have been isolated from retina and other tissues and are of biological relevance. The methodology described will assist in further analytical and biological studies in this field.
- Hamberg, Mats
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p. 489 - 494
(2021/04/19)
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- O,O-Silyl Group Migrations in Quinic Acid Derivatives: An Opportunity for Divergent Synthesis
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The O,O-silyl group migrations on a quinic acid-derived cyclitol have been studied, and the ease of migration was observed to be dependent on the silicon substituents and reaction conditions. Conditions were found to improve the formation of a main isomer during the O,O-silyl group migrations that could be integrated into the formal synthesis of vitamin D receptor modulator VS-105 and in the first total synthesis of a metabolite from the African ant Crematogaster nigriceps.
- Holmstedt, Suvi,Efimov, Alexander,Candeias, Nuno R.
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p. 3083 - 3087
(2021/05/04)
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- Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action
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Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1–2 μM) and fungi Tm and Ca, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M?Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent apoptosis.
- Lyubina, Anna P.,Mironov, Vladimir F.,Pashirova, Tatiana N.,Sapunova, Anastasiia S.,Shaihutdinova, Zukhra M.,Tatarinov, Dmitry A.,Terekhova, Natalia V.,Voloshina, Alexandra D.,Zakharova, Lucia Ya.
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- OLEIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION OR FOOD COMPOSITION COMPRISING SAID OLEIC ACID DERIVATIVES, AND THEIR USES
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This invention relates to oleic acid derivative comprising a hydrophobic part C17H33 linked to a particular polar head part "A", especially for use as a medicament, for instance, for the treatment of a disorder caused by the GPR120 receptor and/or the CD36 receptor, comprising administering to a subject in need thereof a therapeutically effective amount of said oleic acid derivative or of said pharmaceutical composition. The invention also relates to the use of said oleic acid derivative as a food composition.
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- COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF AGENTS
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The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and/or prophylactic agents such as RNA are useful in the delivery of therapeutic and/or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
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-
Paragraph 00725; 00731
(2019/01/08)
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- At Long Last: Olefin Metathesis Macrocyclization at High Concentration
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Macrocyclic lactones, ketones, and ethers can be obtained in the High-Concentration Ring-Closing Metathesis (HC-RCM) reaction in high yield and selectivity at concentrations 40 to 380 times higher than those typically used by organic chemists for similar macrocyclizations. The new method consists of using tailored ruthenium catalysts together with applying vacuum to distill off the macrocyclic product as it is formed by the metathetical backbiting of oligomers. Unlike classical RCM, no large quantities of organic solvents are used, but rather inexpensive nonvolatile diluents, such as natural or synthetic paraffin oils. Moreover, use of a protecting atmosphere or a glovebox is not needed, as the new catalysts are perfectly moisture and air stable. In addition, some other cyclic compounds previously reported as unobtainable by RCM in neat conditions, or in high dilutions even, can be formed with the help of the HC-RCM method.
- Sytniczuk, Adrian,Dabrowski, Micha?,Banach, ?ukasz,Urban, Mateusz,Czarnocka-?niada?a, Sylwia,Milewski, Mariusz,Kajetanowicz, Anna,Grela, Karol
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p. 8895 - 8901
(2018/07/05)
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- Synthesis of Phosphonic Acid Ligands for Nanocrystal Surface Functionalization and Solution Processed Memristors
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Here, we synthesized 2-ethylhexyl, 2-hexyldecyl, 2-[2-(2-methoxyethoxy)ethoxy]ethyl, oleyl, and n-octadecyl phosphonic acid and used them to functionalize CdSe and HfO2 nanocrystals. In contrast to branched carboxylic acids, postsynthetic surface functionalization of CdSe and HfO2 nanocrystals was readily achieved with branched phosphonic acids. Phosphonic acid capped HfO2 nanocrystals were subsequently evaluated as memristors using conductive atomic force microscopy. We found that 2-ethylhexyl phosphonic acid is a superior ligand, combining a high colloidal stability with a compact ligand shell that results in a record-low operating voltage that is promising for application in flexible electronics.
- De Roo, Jonathan,Zhou, Zimu,Wang, Jiaying,Deblock, Loren,Crosby, Alfred J.,Owen, Jonathan S.,Nonnenmann, Stephen S.
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p. 8034 - 8039
(2018/10/25)
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- COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF AGENTS
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The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and/or prophylactic agents such as RNA are useful in the delivery of therapeutic and/or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
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Page/Page column 00836; 00657; 00868; 00663
(2017/07/14)
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- COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS
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This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.
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Page/Page column 326-327
(2017/07/18)
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- Lipid modified spermine derivatives and the use of the derivatives of the prepared liposome
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The invention provides a liposome-modified spermine derivative and a liposome prepared by the derivative. The spermine derivative is directly applied or is mixed with one or more selected from cholesterol, neutral lipids and polyethylene glycol (PEG)-modified lipids, which can be adopted as a carrier for entrapping or absorbing bioactive molecular drugs to be loaded into cells. In this way, the effect of regulation, intervention or treatment is realized. In a general formula (1), X1 represents -(CH2)- or carbonyl group, wherein n represents 1, 2 or 3; X2 represents -(CH2)-, ester group, amide group, oxygen, or sulfur; R1 and R2 independently represent C6-C18 alkyl group or lipophilic cholesterol molecules, respectively.
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Paragraph 0100-0103; 0167-0169; 0172-0173
(2017/08/25)
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- Regioselective phosphorylation of: Myo -inositol with BINOL-derived phosphoramidites and its application for protozoan lysophosphatidylinositol
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A regioselective phosphorylation method for myo-inositol was developed by utilizing readily preparable BINOL-derived phosphoramidites. The method also facilitated the complete separation of the diastereomeric products by simple chromatography. Based on this phosphorylation and Ni-catalyzed alkyl-alkyl cross-coupling reaction for long fatty acids, we achieved the first synthesis of a lysophosphatidylinositol, EhPIa having long fatty acid C30:1, as a partial structure of glycosylphosphatidylinositol (GPI) anchor from the cell membrane of a protozoa, Entamoeba histolytica.
- Aiba, Toshihiko,Sato, Masaki,Umegaki, Daichi,Iwasaki, Takanori,Kambe, Nobuaki,Fukase, Koichi,Fujimoto, Yukari
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supporting information
p. 6672 - 6675
(2016/07/21)
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- Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174
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Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS-specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-activity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and l-serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysoPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174.
- Ikubo, Masaya,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Sayama, Misa,Otani, Yuko,Uwamizu, Akiharu,Suzuki, Keisuke,Kishi, Takayuki,Shuto, Akira,Ishiguro, Jun,Okudaira, Michiyo,Kano, Kuniyuki,Makide, Kumiko,Aoki, Junken,Ohwada, Tomohiko
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p. 4204 - 4219
(2015/06/08)
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- Lipids and compositions for the delivery of therapeutics
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The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alky lhetro cycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).
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Page/Page column 125; 126
(2015/12/04)
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- Water-soluble lipophilic MR contrast agents for cell membrane labeling
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Long-term cell tracking using MR imaging necessitates the development of contrast agents that both label and are retained by cells. One promising strategy for long-term cell labeling is the development of lipophilic Gd(III)-based contrast agents that anch
- Carney, Christiane E.,MacRenaris, Keith W.,Meade, Thomas J.
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p. 971 - 977
(2015/09/01)
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- COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN B
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The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Paragraph 0710; 0711
(2013/05/22)
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- Designing pH-sensitive gemini nanoparticles for non-viral gene delivery into keratinocytes
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This study aimed to develop a more effective non-viral gene delivery system for keratinocyte transfection. To this end, gemini nanoparticles were formulated from plasmid DNA, the lipid DOPE (dioleoylphosphatidylethanolamine) and surfactants, where the sur
- Donkuru, McDonald,Wettig, Shawn D.,Verrall, Ronald E.,Badea, Ildiko,Foldvari, Marianna
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experimental part
p. 6232 - 6244
(2012/06/30)
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- NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF
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The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Page/Page column 120
(2011/12/02)
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- Prenylflavonoids and prenyl/alkyl-phloroacetophenones: Synthesis and antitumour biological evaluation
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Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated acylphloroglucinols have been synthesised as well. In this case the C-alkylation products have resulted, in general, more active.
- Basabe,De Román,Marcos,Diez,Blanco,Bodero,Mollinedo,Sierra,Urones
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experimental part
p. 4258 - 4269
(2010/10/01)
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- Iron-catalyzed 1,4-hydroboration of 1,3-dienes
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(Chemical Equation Presented) A chemo-, regio-, and stereoselective iron-catalyzed 1,4-hydroboration of dienes that affords γ-disubstituted allylboranes has been developed. 1,4-Hydroboration of 2-substituted dienes forms allylborane products with (E)-trisubstituted double bonds exclusively.
- Wu, Jessica Y.,Moreau, Benoit,Ritter, Tobias
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supporting information; experimental part
p. 12915 - 12917
(2009/12/08)
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- Synthesis and solution properties of gemini surfactants containing oleyl chains
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Gemini surfactants 18:1-s-18:1, where s = 2, 3, and 6 methylene groups and 18:1 refers to oleyl carbon chains, have been synthesized, characterized and a number of micelle solution properties measured by using electrical conductance, fluorescence probe em
- Li, Xingfu,Wettig, Shawn D.,Wang, Chuanzhong,Foldvari, Marianna,Verrall, Ronald E.
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p. 3172 - 3178
(2008/02/03)
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- Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone as a new, selective and neutral system for the facile conversion of alcohols, thiols and selenols to alkyl halides in the presence of halide ions
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A mixture of triphenylphosphine (Ph3P) and 2,3-dichloro-5,6-dicyanobenzoquinone in CH2Cl2 affords a complex which in the presence of R4NX (X=Cl, Br, I) converts alcohols, thiols and selenols into their corresponding alkyl halides in high yields at room temperature. The method is highly selective for the conversion of 1° alcohols in the presence of 2° ones and also 1° and 2° alcohols in the presence of 3° alcohols, thiols, epoxides, trimethylsilyl- and tetrahydropyranyl ethers, 1,3 dithianes, disulfides, and amides.
- Iranpoor,Firouzabadi,Aghapour,Vaez zadeh
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p. 8689 - 8693
(2007/10/03)
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- Lipid complexes for transferring at least a therapeutically active substance, in particular a polynucleotide into a target cell and use in gene therapy
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The invention concerns a complex comprising at least a lipid and at least a therapeutically active substance useful for transferring said substance into a target cell, characterised in that said lipid is of formula (I): in which: n1, n2, identical or different are whole numbers between 0 and 1; R1, R2, identical or different are: a) selected among the group consisting of a hydrogen atom and alkyl radicals with 1 to 6 carbon atoms optionally substituted, independently of one another, by a hydroxyl radical; or b) in one particular case for which n1=n2=1, R1and R2can form together a divalent alkylene chain of 2 to 3 carbon atoms (C2-C3); R3, R4, identical or different are alkyl radicals of 1 to 6 carbon atoms or can together form a divalent alkylene chain of 2 to 3 carbon atoms (C2-C3); m, p, identical or different are whole numbers between 1 and 10; R5, R6, identical or different are selected in the group consisting of radicals of formula: 1) R7C(═O)—X— in which: X=NH, O, S; R7is an alkyl or alkenyl radical of 6 to 23 carbon atoms (C6-C23), linear or branched; 2) R8R9NC(═O)— in which: R8, R9, identical or different are selected among the group consisting of the hydrogen atom or alkyl or alkenyl radicals of 6 to 23 carbon atoms, linear or branched, provided that R8, R9, cannot simultaneously correspond to the hydrogen atom; 3) and one of the radicals R5, R6can moreover correspond to the hydrogen atom. The invention also concerns the use of said complex in gene therapy.
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- Synthesis of pyridinium amphiphiles used for transfection and some characteristics of amphiphile/DNA complex formation
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Pyridinium amphiphiles have found practical use for the delivery of DNA into cells. Starting from 4-methylpyridine, a general synthesis has been devised for the production of pyridinium amphiphiles which allows variation in both the hydrophobic part and in the headgroup area of the compounds. By means of differential scanning microcalorimetry, zeta potential, particle size measurements and cryo electron microscopy, some characteristics of the pyridinium amphiphile/DNA complexes have been determined.
- Meekel, Arthur A. P.,Wagenaar, Anno,Smisterova, Jarmila,Kroeze, Jessica E.,Haadsma, Peter,Bosgraaf, Bouke,Stuart, Marc C. A.,Brisson, Alain,Ruiters, Marcel H. J.,Hoekstra, Dick,Engberts, Jan B. F. N.
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p. 665 - 673
(2007/10/03)
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- Quantitative Treatment of the Rotational Dynamics of Flexible-Chain Molecules. 13C NMR Relaxation Study of Hydrocarbon Chains Attached to the Fluorene Anchor
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13C spin-lattice relaxation times (T1) and nuclear Overhauser enhancements (NOEs) were measured for individual carbons in flexible-chain molecules consisting of a hydrocarbon chain attached to fluorene moiety at position 3 through an ester bond.Quantitative treatment of the relaxation data of the ring carbons revealed an anisotropic motion for all the molecules studied.The relaxation times of the chain carbons were analysed in terms of a correlation function describing multiple internal rotations about successive C-C bonds.The results (rotational diffusion constants) were used to discuss features of the chain mobility as a function of chain length and chain unsaturation.The assumptions involved in the quantitative treatment were examined and the values were compared with those of n-alkanes and lipid bilayers. - Keywords: 13C NMR spin-lattice relaxation times Rotational diffusion constants Rotational dynamics Overall and internal motions Hydrocarbon-chain esters of fluorene-3-carboxylic acid
- Pissas, D.,Dais, Photis,Mikros, E.
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p. 263 - 275
(2007/10/02)
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- Synthesis of Very Long Fatty Acid Methyl Esters
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Phosphoranes, produced by treating alkyltriphenylphosphonium bromides with lithium hexamethyldisilazide, reacted with ω-oxo esters to give modest yields of the corresponding methyl cis-alkenoates.By an alternative method, treatment of ω-iodo esters with the complexes formed from reactions of alkylcopper(I) and Grignard reagents gave methyl alkanoates, cis-alkenoates, and methylene-interrupted cis,cis-alka-dienoates and cis,cis,cis-trienoates.The stereochemical integrity of the esters was determined by 13C NMR spectroscopy.
- Kling, Marcel R.,Easton, Christopher J.,Poulos, Alf
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p. 1183 - 1190
(2007/10/02)
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- Tris (trimethylsilyl)silane in the deoxygenation of long chain unsaturated alcohols converts cis to trans isomers
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During radical deoxygenation reactions tris (trimethylsilyl)silane can cause cis to trans isomerization and reduction of remote double bonds in contrast to tributyltin hydride.
- Johnson,Poulos
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p. 2045 - 2048
(2007/10/02)
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- A CONVENITENT PREPARATION OF ALKYL HALIDES AND CYANIDES FROM ALCOHOLS BY MODIFICATION OF THE MITSUNOBU PROSCEDURE
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Alakanols are converted to the corresponding halides and cyanides with inversion of configuration by lithium salts in combination with a preformed complex of diethyl azodicarboxylate and triphenylphosphine.
- Manna, Sukumar,Falck, J. R.,Mioskowski, Charles
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p. 663 - 668
(2007/10/02)
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