- A Convenient Protocol for the Synthesis of Fatty Acid Amides
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Several classes of biologically occurring fatty acid amides have been reported from mammalian and plant sources. Many amides conjugated with fatty acids of mammalian origin exhibit specific activation of individual receptors. Their potential as pharmacological tools or as lead compounds towards the development of novel therapeutics is of great interest. Hence, access to such amides by a practical, high-yielding and scalable protocol without affecting the geometry or position of sensitive functionalities is needed. A protocol that meets all these requirements involves activation of the corresponding acid with carbonyl diimidazole (CDI) followed by reaction with the desired amine or its hydrochloride. More than fifty compounds have been prepared in generally high yields.
- Johansson, Silje J. R.,Johannessen, Tonje,Ellefsen, Christiane F.,Ristun, Mali S.,Antonsen, Simen,Hansen, Trond V.,Stenstrom, Yngve,Nolsoe, Jens M. J.
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supporting information
p. 213 - 217
(2019/01/14)
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- Design, synthesis, and biological evaluation of oxazolidone derivatives as highly potent N-acylethanolamine acid amidase (NAAA) inhibitors
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N-Acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that catalyzes the hydrolysis of endogenous fatty acid ethanolamides (FAEs), such as N-palmitoylethanolamide (PEA). PEA exhibits anti-inflammatory and analgesic activities by engaging peroxisome proliferator-activated receptor α (PPAR-α). Preventing PEA degradation by inhibition of NAAA has been proposed as a novel strategy for the treatment of inflammation and pain. In the present study, we reported the discovery of the oxazolidone derivative as a novel scaffold for NAAA inhibitors, and studied the structure-activity relationship (SAR) by modification of the side chain and terminal lipophilic substituents. The results showed that the link chain length of C5, straight and saturated linkages were the preferred shape patterns for NAAA inhibition. Several nanomolar NAAA inhibitors were described, including 2f, 3h, 3i and 3j with IC50 values of 270 nM, 150 nM, 100 nM and 190 nM, respectively. Enzymatic degradation studies suggested that 2f inhibited NAAA in a selective, noncompetitive and reversible pattern. Moreover, 2f showed high anti-inflammatory and analgesic activities after systemic and oral administration.
- Ren, Jie,Li, Yuhang,Ke, Hongwei,Li, Yanting,Yang, Longhe,Yu, Helin,Huang, Rui,Lu, Canzhong,Qiu, Yan
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p. 12455 - 12463
(2017/03/11)
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- Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides
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The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The
- Tona, Veronica,De La Torre, Aurélien,Padmanaban, Mohan,Ruider, Stefan,González, Leticia,Maulide, Nuno
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supporting information
p. 8348 - 8351
(2016/07/26)
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- Antiproliferative activity of synthetic fatty acid amides from renewable resources
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In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line - the most aggressive CNS cancer.
- Dos Santos, Daiane S.,Piovesan, Luciana A.,D'Oca, Caroline R. Montes,Hack, Carolina R. Lopes,Treptow, Tamara G.M.,Rodrigues, Marieli O.,Vendramini-Costa, Débora B.,Ruiz, Ana Lucia T.G.,De Carvalho, Jo?o Ernesto,D'Oca, Marcelo G. Montes
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supporting information
p. 340 - 347
(2015/02/02)
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- Mesoporous silica MCM-41 as a highly active, recoverable and reusable catalyst for direct amidation of fatty acids and long-chain amines
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Direct amidation of fatty acids with long-chain amines was successfully performed by mesoporous silica MCM-41, which showed the highest catalytic activity among other used homo- and heterogeneous catalysts. It was found that MCM-41 can be easily recovered from the reaction mixture followed by simple calcination treatment and reused without loss of its catalytic activity. The Royal Society of Chemistry.
- Komura, Kenichi,Nakano, Yu,Koketsu, Mamoru
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experimental part
p. 828 - 831
(2011/05/15)
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- Eicosapentaenoic acid enrichment from sardine oil by argentation chromatography
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Eicosapentaenoic acid (EPA) derived from chemically hydrolyzed sardine oil was concentrated by urea fractionation using methanol at different temperatures (2, 4, and 6°C) and urea/fatty acid ratios (2:1, 3:1, and 4:1 w/w) and purified by argentation neutral alumina column chromatography. The individual fatty acids were determined as fatty acid methyl esters (FAME) by gas-liquid chromatography and gas chromatography-mass spectroscopy as FAME and N-acyl pyrrolidides. In the mass fragmentation pattern of FAME, the base peak was assigned to be the 1-methoxyethenol moiety (m/z = 74) obtained by McLafferty rearrangement. Formation of the cyclic tropylium ion (m/z = 91) in fatty acids with four or more double bonds was apparent in FAME-PUFAs. The base peak of N-acyl pyrrolidides was the McLafferty rearrangement ion, 1-(pyrrolidin-1-yl) ethenol (m/z = 113). The highest concentration of EPA (47.78%) was obtained at the crystallization temperature of 4°C with a urea/fatty acid ratio of 4:1 (w/w) with 93.74% yield. After complexation of saturated and less unsaturated fatty acids by urea complexation, argentation chromatography resulted in an EPA of high purity (99.6%) with an overall recovery of 54.09% using 50% diethyl ether/n-hexane as eluting solvent. The peroxide (POV) and thiobarbituric acid (TBS) values were found to be highest (4.0 mequiv of O2/kg and 5.2 mg of malondialdehyde/kg, respectively) during urea fractionation at the higher crystallization temperature (6°C) and higher urea/fatty acid ratio (4:1).
- Chakraborty, Kajal,Raj, R. Paul
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p. 7586 - 7595
(2008/09/19)
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- One pot direct synthesis of amides or oxazolines from carboxylic acids using Deoxo-Fluor reagent
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A mild and highly efficient one pot-one step condensation and/or condensation-cyclization of various acids to amides and/or oxazolines using Deoxo-Fluor reagents is described. Parallel syntheses of various free fatty acids with 2-amino-2,2-dimethyl-1-propanol resulted with excellent yields.
- Kangani, Cyrous O.,Kelley, David E.
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p. 8917 - 8920
(2007/10/03)
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- Aliphatic pyrrolidine amides from two tropical convolvulaceous species
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Seven aliphatic pyrrolidine amides with branched and linear saturated C15-C19 acyl moieties were detected in vegetative plant organs of Ipomoea aquatica and Merremia quinquefolia as well as in seeds of M. quinquefolia by GC-MS analysis. One of the compounds was isolated from both species and characterized as 1-(14-methylhexadecanoyl)pyrrolidine, a new natural product. The presence of 1-hexadecanoylpyrrolidine and 1-octadecanoylpyrrolidine was confirmed by comparison of their GC-MS data with those of synthesized compounds.
- Tofern, Britta,Mann, Petra,Kaloga, MacKi,Jenett-Siems, Kristina,Witte, Ludger,Eich, Eckart
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p. 1437 - 1441
(2007/10/03)
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- Dermal penetration enhancement profile of hexamethylenelauramide and its homologues: In vitro versus in vivo behavior of enhancers in the penetration of hydrocortisone
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Several amides of cyclic amines were prepared and tested as penetration enhancers in the diffusion of various drugs through hairless mouse skin in vitro. Hexamethylenelauramide (hexahydro-1-lauroyl-1H-azepine) was selected as a broad spectrum penetration enhancer worthy of further study. Later, the duration of the effect of various enhancers on the penetration barrier in vivo was determined by evaluating the in vitro diffusion of hyrocortisone through skins that had been pretreated in vivo. We found that the longer the pretreatment, the smaller the amount of penetrated hydrocortisone. Furthermore, our results suggested that differences exist in the retention of various enhancers in living mouse skin. The in vitro pretreatment experiments revealed that the penetration through dead skin is slow compared with the penetration through living skin. Neither the nature of the receptor phase, nor the increased temperature of the in vitro experiments, explain the striking differences between the in vivo and the in vitro experiments. Finally, the penetration of hydrocortisone through the stratum corneum in the presence of enhancers, as well as the penetration of 1-dodecylhexahydro-2H-azepin-2-one (laurocapram), hexamethylenelauramide, and oleic acid, were determined using a stratum corneum stripping technique. More hydrocortisone penetrated through the stratum corneum during the first 3 h in the presence of hexamethylenelauramide than in the presence of laurocapram or oleic acid.
- Mirejovsky,Takruri
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p. 1089 - 1093
(2007/10/02)
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- Monitored Aminolysis of 3-Acyl-1,3-thiazolidine-2-thiones: Synthesis of Amides and Amide Alkaloids
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A functional heterocycle, 3-acyl-1,3-thiazolidine-2-thione has been shown to be effective as an acylating reagent for the amino group.ATT (1) was readily prepared by several methods, and reacted with various amino compounds in CHCl3, CH2Cl2, THF, EtOH, THF-H2O, or sulfolane to afford the corresponding amides, 2a-w and 3-10 in very high yields within a short time.This reagent exhibits high chemo-selectivity.Its reaction with the diamines 13 and 15 and the triamine 29, which include a primary amino group(s) and a secondary amino group, gave the products acylated only at the primary amino group(s), 14, 16, and 30, respectively, in high yields.Aminoalcohols and aminophenols were chemoselectively converted into acylaminoalcohols and acylaminophenols, respectively, by ATT (1).By utilizing this method, several amide alkaloids (26, 28, 30, and 34) were efficiently synthesized.This new aminolysis can be monitored by the disappearance of the yellow color of the starting materials, ATT (1); it is remarkably characteristic of this reaction. Keywords - monitored aminolysis; 3-acyl-1,3-thiazolidine-2-thione; high chemo-selectivity; amide synthesis; fagaramide; dolicotheline; spermidine; maytenine; N-ferulyltryptamine
- Nagao, Yoshimitsu,Seno, Kaoru,Kawabata, Kohji,Miyasaka, Tadao,Takao, Sachiko,Fujita, Eiichi
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p. 2687 - 2699
(2007/10/02)
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- MONITORED AMINOLYSIS OF 3-ACYLTHIAZOLIDINE-2-THIONE : A NEW CONVENIENT SYNTHESIS OF AMIDE
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3-Acylthiazolidine-2-thiones (1) were easily prepared and they were treated with several amines in dichloromethane to give amides 4 in very high yields within a short time.Aminoalcohols and aminophenols were selectively converted into acylaminoalcohols and acylaminophenols, respectively, by this reaction.One can monitor the reaction by disappearance of the yellow color of the starting material 1.Some amide alkaloids (15-18) have effectively been synthesized.
- Nagao, Yoshimitsu,Seno, Kaoru,Kawabata, Kohji,Miyasaka, Tadayo,Takao, Sachiko,Fujita, Eiichi
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p. 841 - 844
(2007/10/02)
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