- ONE-STEP SYNTHESIS OF ω-HYDROXYCARBOXYLIC ACIDS BY THE REACTION OF ω-METALOXYLATED GRIGNARD REAGENTS WITH β-PROPIOLACTONES
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ω-Metaloxylated Grignard reagents reacted with β-propiolactones chemo- and regioselectively in the presence of Li2CuCI4 to afford ω-hydroxycarboxylic acids in high yields.
- Fujisawa, Tamotsu,Mori, Toshiki,Kawara, Tatsou,Sato, Toshio
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- Practical syntheses of some insect sex pheromones, 10- and 12-alken-1-ol acetates
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Some insect sex pheromones 10-dodecen-1-ol acetates 5a(Z/E) and 12-tetradecen-1-ol acetates 5b(Z/E) have been synthesized from cis-13-docosenoic acid 1a and cis-15-tetracosenoic acid 1b via the isomerization of key intermediates 11-dodecen-1-ol acetate 4a and 13-tetradodecen-1-ol acetate 4b.
- Jun,Fuchu,Youchu,Mei
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Read Online
- Novel insights into oxidation of fatty acids and fatty alcohols by cytochrome P450 monooxygenase CYP4B1
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CYP4B1 is an enigmatic mammalian cytochrome P450 monooxygenase acting at the interface between xenobiotic and endobiotic metabolism. A prominent CYP4B1 substrate is the furan pro-toxin 4-ipomeanol (IPO). Our recent investigation on metabolism of IPO related compounds that maintain the furan functionality of IPO while replacing its alcohol group with alkyl chains of varying structure and length revealed that, in addition to cytotoxic reactive metabolite formation (resulting from furan activation) non-cytotoxic ω-hydroxylation at the alkyl chain can also occur. We hypothesized that substrate reorientations may happen in the active site of CYP4B1. These findings prompted us to re-investigate oxidation of unsaturated fatty acids and fatty alcohols with C9–C16 carbon chain length by CYP4B1. Strikingly, we found that besides the previously reported ω- and ω-1-hydroxylations, CYP4B1 is also capable of α-, β-, γ-, and δ-fatty acid hydroxylation. In contrast, fatty alcohols of the same chain length are exclusively hydroxylated at ω, ω-1, and ω-2 positions. Docking results for the corresponding CYP4B1-substrate complexes revealed that fatty acids can adopt U-shaped bonding conformations, such that carbon atoms in both arms may approach the heme-iron. Quantum chemical estimates of activation energies of the hydrogen radical abstraction by the reactive compound 1 as well as electron densities of the substrate orbitals led to the conclusion that fatty acid and fatty alcohol oxidations by CYP4B1 are kinetically controlled reactions.
- Thesseling, Florian A.,Hutter, Michael C.,Wiek, Constanze,Kowalski, John P.,Rettie, Allan E.,Girhard, Marco
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- Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors
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We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure–activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological profiles. The connection of two weak ligands—N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC50] = 8.6 μM) and 2-(methylthio)benzo[d]oxazole (IC50 = 31 μM)—via a linker comprising a 6 methylene group chains yielded a highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50 = 0.004 μM) toward aortic ACAT. This head-to-tail design made it possible to markedly enhance the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity based on the double-induced fit mechanism. At doses of 1 and 3 mg/kg, 3h significantly decreased the lipid-accumulation areas in the aortic arch to 74 and 69%, respectively without reducing the plasma total cholesterol level in high fat- and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic effect of 3h in vivo via its direct action on aortic ACAT and its powerful modulator of cholesterol level. This molecule is a potential therapeutic agent for the treatment of diseases involving ACAT-1 overexpression.
- Shibuya, Kimiyuki,Kawamine, Katsumi,Miura, Toru,Ozaki, Chiyoka,Edano, Toshiyuki,Mizuno, Ken,Yoshinaka, Yasunobu,Tsunenari, Yoshihiko
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p. 4001 - 4013
(2018/06/26)
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- Mild and chemoselective lactone ring-opening with (TMS)ONa. Mechanistic studies and application to sweroside derivatives
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Mild and chemoselective opening of lactones with sodium trimethylsilanolate in high yields and aprotic solvents is described. Kinetic studies demonstrate that the BAc2 mechanistic pathway is followed. Nucleophilic attack of silanolate onto the carbonyl of the lactone moiety is the rate-determining step. NaOH present as an impurity accelerates the reaction. The method was further applied to the base-sensitive and stable lactones derived from highly functionalized iridoid derivatives.
- Lemoine, Hugues,Markovi?, Dean,Deguin, Brigitte
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p. 4358 - 4366
(2014/06/09)
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- A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues
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The cyclic peptide core of the antifungal and antibiotic cyclic depsipeptide LI-F04a was synthesised by using a modified Yamaguchi macrolactonization approach. Alternative methods of macrolactonization (e.g., Corey-Nicolaou) resulted in significant epimerization of the C-terminal amino acid during the cyclization reaction. The D-stereochemistry of the alanine residue in the naturally occurring cyclic peptide may be required for the antifungal activity of this natural product.
- Cochrane, James R.,Yoon, Dong Hee,McErlean, Christopher S.P.,Jolliffe, Katrina A.
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supporting information
p. 1344 - 1351
(2012/11/07)
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- Indium tribromide catalyzed cross-Claisen condensation between carboxylic acids and ketene silyl acetals using alkoxyhydrosilanes
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Acylations achieved: The title reaction between carboxylic acids and ketene silyl acetals has been accomplished (see scheme). The additive, (MeO) 3SiH, is believed to play an important role in the promotion of the condensation reaction. This reaction system was compatible with a diverse range of functional groups, including alkenes, alkynes, chlorides, alcohols, esters, and nitro groups. Copyright
- Nishimoto, Yoshihiro,Okita, Aya,Yasuda, Makoto,Baba, Akio
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supporting information; experimental part
p. 8623 - 8625
(2011/11/06)
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- Synthesis of ω-hydroxy carboxylic acids and α,ωdimethyl ketones using α,ω-diols as alkylating agents
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"Chemical equation presented" Synthesis of ω-hydroxy carboxylic acids and α,ω-dimethyl diketones was successfully achieved by using α,ω-diols as alkylating agents under the influence of an iridium catalyst. For example, the alkylation of butyl cyanoacetate with 1,13-tridecanediol in the presence of [IrCl(cod)]2 or [rrCl(coe) 2]2 gave rise to butyl 2-cyano-15-hydroxypentadecanoate in good yield which is easily converted to cyclopentadecanolide (CPDL). In addition, the alkylation of acetone with 1,10-decanediol in the presence of [IrCl(cod)]2 and KOH resulted in an important muscone precursor, 2,15-hexadecanedione (HDDO), in good yield.
- Iuchi, Yosuke,Hyotanishi, Megumi,Miller, Brittany E.,Maeda, Kensaku,Obora, Yasushi,Ishii, Yasutaka
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supporting information; experimental part
p. 1803 - 1806
(2010/05/17)
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- Enzymatic aminolysis of lactones in aqueous miniemulsion: Catalysis through a novel pathway
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Lipase-catalyzed aminolysis of lactones under aqueous conditions usually leads to the hydrolysis of the ester bond with only a minor content of the corresponding amide. However, the aminolysis of pentadecanolide (PD) and hexadecanolide (HD), respectively, with oleylamine (OA) in aqueous miniemulsion under optimized conditions (temperature, concentration of enzyme, reaction time) yields >90% amide. Kinetic investigations performed with OA and PD reveal that the lipase catalyzes a novel reaction pathway, i.e., the hydrolysis of a lactone followed by the amidation requiring 30. min and 8 days reaction time, respectively. The demands of a high amount of lipase as well as the long reaction time are caused by the low reactivity of the carboxylic group and the formation of salt with the amine. Similar reactions were performed with PD and other amines such as dodecyl, decyl, octyl, benzyl and hexyl amine resulting the analogous amide compounds.
- Ragupathy, Laks,Pluhar, Bettina,Ziener, Ulrich,Keller, Harald,Dyllick-Brenzinger, Rainer,Landfester, Katharina
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experimental part
p. 270 - 276
(2010/11/16)
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- Simple preparation of highly pure monomeric ω-hydroxycarboxylic acids
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Highly pure monomeric ω-hydroxycarboxylic acids (HCAs) with ≥C6 are prepared from their corresponding lactones or alkyl ω-hydroxycarboxylates through saponification followed by H 2SO4 acidification and treatment at 35-40 °C/8-12 mbar or by freeze-drying. The HCA is being formed through its sodium or potassium salt and is obtained in 80-85% yield with >99.5% purity, uncontaminated with dimers. This simple procedure excludes chromatographic purification.
- Stephan, Michel Massoud S.,Mohar, Barbara
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p. 481 - 483
(2012/12/22)
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- Amphiphilic [5:1]- and [3:3]-hexakisadducts of C60
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We have synthesized and characterized a variety of new amphiphilic hexakisadducts of C60 involving mixed octahedral [5:1]- and [3:3]-addition patterns. The [5:1]-adducts 3 and 13 contain five pairs of didodecyl or diethyl malonates as non-polar addends and, as their polar part, an extended bis(malonate) involving C14 and ethylene glycol chains and two biotin termini. For the first time, amphiphilic [3:3]-hexakisadducts have been prepared using the e,e,e-trisadduct 18, which contains a cyclo-[3]-octyl malonate addend, as the precursor. As polar groups, we used malonates featuring carboxy, amino, or peptide termini. The charge on the termini, which can range from zero up to sixfold positive or sixfold negative, can be built up by protonation or deprotonation. All the amphiphilic [3:3]-hexakisadducts are very soluble in water in their completely charged forms. Initial investigations on the aggregation properties of the amphiphilic [3:3]-hexakisadducts, conducted using transmission electron microscopy (TEM) and pulse-gradient spin echo (PGSE) NMR spectroscopy, reveal the pH-dependent formation of aggregates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Braun, Martin,Hartnagel, Uwe,Ravanelli, Elena,Schade, Boris,Boettcher, Christoph,Vostrowsky, Otto,Hirsch, Andreas
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p. 1983 - 2001
(2007/10/03)
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- Anticancer agents, perfumes or foods and drinks containing omega-hydroxyfatty acids
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The present invention relates to drugs and, particularly, to anticancer agents. More particularly, the present invention relates to an anticancer agents containing, as an active ingredient, at least one compound selected from the group consisting of ω-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters having specific chemical structures. With respect to the compounds described above used in the present invention, since the activities of killing cancer and inhibiting cancer metastasis are significantly high, the effects of preventing the recurrence of cancer and preventing cancer are exhibited, the cytotoxicity is significantly low, and a small dose is effective, it is possible to provide anticancer agents having significantly decreased side effects. Additionally, use in combination with known antitumor agents can further enhance the activity of inhibiting cancer metastasis. Among the anticancer agents of the present invention, ω-hydroxy fatty acids can be easily obtained in high purities by hydrolyzing lactones which are also the anticancer agents of the present invention.
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- Simplified syntheses of polymerizable bis-substituted phosphatidylcholines with various chain lengths
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Syntheses of new compounds, 1,2-bis[15-(2',4'-hexadienoyloxy)pentadecanoyl]- and 1,2-bis[15-(2',4'-hexadienoyloxy)dodecanoyl]-sn-glycero-3-phosphatidylcholine s, via a simplified procedure are reported. The new approach utilizes the conversion of commercially available lactones into polymerizable bis-substituted phosphatidylcholines after two steps of reaction. (C) 2000 Elsevier Science Ltd.
- Bae,Kim,Kim,Koo,Ryeom,Ryeom,Fu,Chang
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p. 8495 - 8498
(2007/10/03)
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- Phytosphingosine-based ceramide I analogs
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The present invention describes phytospringosine-based analogs of ceramides I, as well as cosmetics and pharmaceutical compositions containing these novel compounds and their use.
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- Method for producing 2-(ω-alkoxycarbonyl alkanoyl)-4-butanolide and a long-chain ω-hydroxycarboxylic acid
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2-(ω-alkoxycarbonyl alkanoyl)-4-butanolide can be produced unexpectedly with a high selectivity and yield through condensation reaction of γ-butyrolactone with a highly available, loω-price dicarboxylate as represented by the following general formula: (where n denotes an integer of 7-13, and R denotes an alkyl group or an alkenyl group). Furthermore, a long-chain ω-hydroxycarboxylic acid can be produced by subjecting 2-(ω-alkoxycarbonyl alkanoyl)-4-butanolide to hydrolysis and decarboxylation and reducing the carbonyl groups in the resultant product into methylene groups.
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- Process for preparing lactones and intermediates therefor
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Described is a process for preparing cyclopentadecanolide defined according to the structure: STR1 using as a starting material the dicarboxylic acid having the structure: STR2 according to the reaction sequence: STR3 Also described is a process for using the resultant cyclopentadecanolide for augmenting, enhancing or imparting aromas in or to perfume compositions, colognes and perfumed articles including but not limited to solid or liquid anionic, cationic, nonionic or zwitterionic detergents, perfumed polymers, fabric softener compositions, fabric softener articles, cosmetic powders and hair preparations.
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- Process of preparing ω-hydroxy acids
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A new synthesis of ω-hydroxy acids, which employs commercially available starting materials and lowers the cost of production. The process involves coupling a fatty acyl group by enamine chemistry, followed by a ring expansion and selective reduction of ketoacid.
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- Process for producing ω-hydroxy fatty acids
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ω-Hydroxy fatty acids usable for the synthesis of medicaments, perfumes and polymers are produced by subjecting an alkali or alkaline earth metal salt of long-chain dicarboxylic acid monoester to a reduction with a borohydride compound or catalytic hydrogenating reduction treatment.
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- Process for producing omega-hydroxy fatty acids
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ω-Hydroxy fatty acids usable for the synthesis of medicaments, perfumes and polymers are produced by subjecting an alkali or alkaline earth metal salt of long-chain dicarboxylic acid monoester to a reduction with a borohydride compound or catalytic hydrogenating reduction treatment.
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- Process for producing omega-hydroxy fatty acids
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A process of producing an ω-hydroxy fatty acid by the step of hydrogenation of a long-chain dicarboxylic acid monoester in the presence of a copper-chromium oxide catalyst. According to the process of the invention, ω--hydroxy fatty acids which are useful in the synthesis of medicaments and in the synthesis of macrocyclic lactones which are used for perfumes, etc. and of various polymers can be produced at low production cost and with good efficiency, using inexpensive raw materials by a simplified procedure.
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- Synthese de lactones a cycle moyen: Application a la synthese du pentadecanolide-15 et du phoracantholide I
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Medium ring size lactones can be prepared from bifunctional commercial starting compounds in high yields, using a few step sequence.Lactonisation is obtained by cyclization of the free ω-hydroxyacids or by the cyclization of ω-hydroxyacids having the hydroxy and carboxy group protected.
- Cossy, Janine,Pete, Jean-Pierre
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p. 989 - 994
(2007/10/02)
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- A THREE STEP SYNTHESIS OF EXALTOLIDE AND PHORACANTHOLIDE I
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The synthesis of phoracantholide I and exaltolide are described in 3 steps and in good yields.
- Cossy, J.,Pete, J.P.
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p. 2369 - 2370
(2007/10/02)
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- Acides gras marques en position ω par un nucleide radioactif emetteur γ
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The synthesis of many saturated, acetylenic, olefinic (Z or E) fatty acids labeled with 123I or 131I at the ω-position has been achieved.The radioactive iodine atom is introduced by a I-, *I- exchange reaction; the influence on the yield of several parameters - presence of iodine carrier, fatty acid and water concentrations, solution acidity - has been studied.Experimental conditions which produce labeling yields higher than 95percent have been defined; these results have lead to a very easy labeling method used in several hospitals in the external study of myocardial metabolism of fatty acids.
- Riche, Francoise,Mathieu, Jean-Paul,Vincens, Maurice,Bardy, Andre,Comet, Michel,Vidal, Michel
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- A New and Effective Synthetic Method for the Preparation of the Esters, Peptides, and Lactones Using 3-(5-Nitro-2-oxo-1,2-dihydro-1-pyridyl)-1,2-benzisothiazole 1,1-Dioxide. Synthesis of (+/-)-E-Dodecen-11-olide, Recifeiolide
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3-(5-nitro-2-oxo-1,2-dihydro-1-pyridyl)-1,2-benzisothiazole 1,1-dioxide (BID-NPy), readily prepared from 3-chloro-1,2-benzisothiazole 1,1-dioxide and 5-nitro-2-pyridone, proved to be a very useful condensing reagent.A variety of esters, dipeptides, and lactones were obtained in excellent yields.Furthemore, BID-NPy was successfully employed for the lactonization step in a new synthesis of a naturally occuring (+/-)-(E)-8-dodecen-11-olide, recifeiolide.
- Ahmed, Alauddin,Taniguchi, Nagahiro,Fukuda, Hirohiko,Kinoshita, Hideki,Inomata, Katsuhiko,Kotake, Hiroshi
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p. 781 - 786
(2007/10/02)
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- Synthesis of 14-hydroxytetra- and 15-hydroxypentadecanoic acids
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14-Hydroxytetradecanoic and 15-hydroxypentadecanoic acids were synthesized from 1,10-decanedicarboxylic and 1,11-undecanedicarboxylic acids.The diesters of the latter were reduced to the diols, from which the chlorohydrins were obtained by reaction with hydrogen chloride.The use of these chlorohydrins in the sodiomalonic synthesis leads to the hydroxy carboxylic acids.
- Zakharkin, L. I.,Guseva V. V.,Pryanishnikov A. P.
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p. 658 - 661
(2007/10/02)
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- Oxidation of Hydrazines with Benzeneseleninic Acid and Anhydride
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Benzeneseleninic acid (1) and anhydride (2) oxidize hydrazine or 1,2-disubstituted derivatives to corresponding diazenes.Hydrazides afford selenoesters 4, N,N'-diacyl- or diaroylhydrazines 5, and carboxylic acids.Benzeneselenenic acid (7) is a required intermediate in selenoester formation and may be generated independently by the reaction of triphenylphosphine with 1.Selenoesters are efficiently prepared by the slow addition of a mixture of the hydrazide and triphenylphosphine to 1 in dichloromethane solution.Polar solvents are unsuitable.Inverse addition provides compounds 5 as major products.Oxidation of hydrazides of structure HO-(CH2)nCONHNH2 gives the corresponding selenoesters 14 and acids 16 when n=11 or 14 lactones 17 and 18 when n=4 or 3.Arylhydrazines react with 1 or 2 to furnish arenes 23 and aryl phenyl selenides 24.
- Back, Thomas G.,Collins, Scott,Ker, Russell G.
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p. 1564 - 1570
(2007/10/02)
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- Effect of Inverse Micelles on the Competition between Lactonization and Polymerization Reactions of an ω-Hydroxy Carboxylic Acid
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The ability of inverse micelles to influence the competition between carbodiimide-mediated lactonization and polymerization of 15-hydroxypentadecanoic acid (1), yielding pentadecanolide (2) and polymer (3), respectively, has been investigated by using inverse micellar systems in benzene based on di-n-dodecyldimethylammonium bromide (DDABr) and on bis(2-ethylhexyl) sodium sulfosuccinate (AOT) with and without water pools.Two ionic carbodiimides, 1-cyclohexyl-3-carbodiimide p-toluenesulfonate (4) and 1--3-ethylcarbodiimide hydrochloride (5), were used.The inherent ability of carbodiimide 4 to effect lactonization of 1 is inhibited moderately by DDABr inverse micelles without water pools and completely by AOT inverse micelles without water pools.Carbodiimide 4 did not effect esterification when these inverse micellar systems contained water pools; carbodiimide 5 apparently did not do so under any of the conditions used.
- Jaeger, David A.,Ippoliti, J. Thomas
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p. 4964 - 4968
(2007/10/02)
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- A NEW METHOD FOR THE PRODUCTION OF 15-HYDROXYPENTADECANOIC ACID
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15-Hydroxypentadecanoic acid was synthesized by electrochemical condensation of monoethyl 1,10-decanedicarboxylate with 5-acetoxyvaleric acid at a platinum anode.The acetoxyvaleric acid was obtained in two ways, i.e., by acetolysis of 5-chlorovaleric acid and by oxidation of cyclopentanone by peracetic acid in acetic acid.
- Andreev, V. M.,Polyakova, S. G.,Bazhulina, V. I.,Khrustova, Z. S.,Smirnova, V. V.,etc.
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- Omega-hydroxy or acyloxy-alkyl-γ-butyrolactones
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Process for preparing omega-hydroxy fatty acids of the formula wherein R is H or acyl, and n is an integer of 0 to 18, by a very simple operation without a trouble of pollution, which comprises catalytically reacting an omega-hydroxy (or acyloxy)-alkyl-γ-butyrolactone of the formula STR1 wherein R and n are as defined above, in the presence of a hydrogenolysis catalyst. Compounds of formula (2) are novel, and a process for preparing them is also provided.
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- SYNTHESE DE MACROLIDES PAR METATHESE.
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Two syntheses of macrolides via olefin metathesis are presented.The first (A) involves preparation of ω-hydroxyacid 6 or 9 by metathesis followed by cyclisation, while the second (B) involves macrocyclic ring closure by metathesis of a ω,ω'diunsaturated ester 12.
- Villemin, Didier
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p. 1715 - 1718
(2007/10/02)
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- Process for the preparation of cyclopentadecanolide
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Process for the preparation of cyclopentadecanolide comprising the steps of converting 13-oxa-bicyclo [10.4.0]-hexadecene-[1(12)] to a lactone of the formula STR1 wherein X is an oxygen atom, =NOH or =N--NH2, reducing said lactone to give 15-hydroxy-pentadecanecarboxylic acid and cyclising said acid to give cyclopentadecanolide.
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