- Exploring the effect of chirality on the therapeutic potential of N-alkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease
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In the frame of a research program aimed to explore the relationship between chirality of iminosugars and their therapeutic potential, herein we report the synthesis of N-akyl L-deoxyiminosugars and the evaluation of the anti-inflammatory properties of selected candidates for the treatment of Pseudomonas aeruginosa infections in Cystic Fibrosis (CF)lung disease. Target glycomimetics were prepared by the shortest and most convenient approach reported to date, relying on the use of the well-known PS-TPP/I2 reagent system to prepare reactive alkoxyalkyl iodides, acting as key intermediates. Iminosugars ent-1-3 demonstrated to efficiently reduce the inflammatory response induced by P. aeruginosa in CuFi cells, either alone or in synergistic combination with their D-enantiomers, by selectively inhibiting NLGase. Surprisingly, the evaluation in murine models of lung disease showed that the amount of ent-1 required to reduce the recruitment of neutrophils was 40-fold lower than that of the corresponding D-enantiomer. The remarkably low dosage of the L-iminosugar, combined with its inability to act as inhibitor for most glycosidases, is expected to limit the onset of undesired effects, which are typically associated with the administration of its D-counterpart. Biological results herein obtained place ent-1 and congeners among the earliest examples of L-iminosugars acting as anti-inflammatory agents for therapeutic applications in Cystic Fibrosis.
- De Fenza, Maria,D'Alonzo, Daniele,Esposito, Anna,Munari, Silvia,Loberto, Nicoletta,Santangelo, Alessandra,Lampronti, Ilaria,Tamanini, Anna,Rossi, Alice,Ranucci, Serena,De Fino, Ida,Bragonzi, Alessandra,Aureli, Massimo,Bassi, Rosaria,Tironi, Matteo,Lippi, Giuseppe,Gambari, Roberto,Cabrini, Giulio,Palumbo, Giovanni,Dechecchi, Maria Cristina,Guaragna, Annalisa
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supporting information
p. 63 - 71
(2019/05/10)
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- A powerful tool for acid catalyzed organic addition and substitution reactions
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A novel green chemistry tool for acid catalyzed reactions has been developed. The multipurpose tool is based on the ability of dry solid materials to donate protons (H+) to starting materials combined with the simultaneous use of a nucleophile (e.g. NaI). The methods enable the following reactions to be conducted at 20-50 °C: selective addition of iodine or alcohols to more substituted carbon in R2CCH2 systems (R ≠ H), esterification reactions, e.g. free fatty acids with methanol, and at higher temperatures, (60-100 °C): esterification of free fatty acids with hindered alcohols (isopropanol), addition of iodine to CC bonds, opening of oxygen(s) containing heterocyclic rings, selective substitution of primary OH groups to iodine in the presence of other functional groups or secondary alcohol groups, esterification of alcohols with nitriles (R-CN), transesterification of fatty acid triglycerides to biodiesel and selective derivatization of primary hydroxyl groups (-CH2OH) over secondary moieties of sugars without any protection. Most of the reactions were also performed by a re-used Dowex cation exchange resin.
- Turhanen, Petri A.,Veps?l?inen, Jouko J.
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p. 26218 - 26222
(2015/10/20)
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- Pheromone synthesis. Part 243: Synthesis and biological evaluation of (3R,13R,1′S)-1′-ethyl-2′-methylpropyl 3,13-dimethylpentadecanoate, the major component of the sex pheromone of Paulownia bagworm, Clania variegata, and its stereoisomers
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All of the four stereoisomers of (1′S)-1′-ethyl-2′-methylpropyl 3,13-dimethylpentadecanoate, the major component of the female sex pheromone of Clania variegata, were synthesized by employing olefin cross metathesis as the key reaction and starting from (R)- or (S)-2-methyl-1-butanol, (R)- or (S)-citronellal, and (S)-2-methyl-3-pentanol. Their bioassay revealed the (3R,13R,1′S)-isomer as the bioactive one, whose more efficient synthesis was achieved in two different ways by employing Wittig reaction as the key step.
- Mori, Kenji,Tashiro, Takuya,Zhao, Boguang,Suckling, David M.,El-Sayed, Ashraf M.
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experimental part
p. 2642 - 2653
(2010/05/18)
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- Functional transformation of aldehydes and ketones via homolytic induced decomposition of unsaturated peroxy acetals and peroxy ketals
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Induced decomposition of unsaturated peroxy acetals prepared from trimethyl orthoformate, dodecanal or 2-methyl-undecanal and 2,3-dimethyl-2-hydroperoxybut-3-ene, in the presence of ethyl iodoacetate, CC14 or dodecanethiol, allowed respectively their iodo-, chloro- and hydro-decarbonylation with yields of over 70%; the same reaction applied to the monoperoxy ketal or diperoxy ketal of cyclohexanone in the presence of ethyl iodoacetate resulted in its functional transformation in methyl 6-iodohexanoate or 1,5-diiodopentane with respective yields of 65 and 40%.
- Moutet,Bonafoux,Degueil-Castaing,Maillard
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p. 139 - 140
(2007/10/03)
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- Diiodosilane. 2. A Multipurpose Reagent for Hydrolysis and Reductive Iodination of Ketals, Acetals, Ketones, and Aldehydes
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The reaction patterns of diiodosilane (SiH2I2, DIS) with ketals, acetals, ketones, and aldehydes were explored.The reagent may be used for mild cleavage of ketals and acetals either hydrolytically to give the parent carbonyl functionality or reductively to produce the corresponding alkyl iodide.At low temperatures (-42 deg C) and short reaction times (few minutes), catalytic amounts (5-10 molpercent) of DIS provide clean deprotection of various ketals and acetals to yield ketones and aldehydes, with no apparent reduction of the latter.At temperatures above 0 deg C, DIS effectively reduces ketals and acetals to iodoalkanes.This reduction is quite general both with respect to ketals and acetals and unprotected ketones and aldehydes.Reaction rates, however, are strikingly dependent on the substrate, with the following tendencies: (a) aromatic functionalities are generally reduced much faster than their aliphatic analogues; (b) ketals and acetals are rapidly reduced to the corresponding iodoalkanes, while free aldehydes, and particularly ketones, are essentially inert under the reaction conditions (but can be significantly activated by catalytic amounts of iodine); (c) dimethyl ketals form the parent ketones preferentially, while all other ketals, including diethyl ketals and dioxolanes, are reduced to iodoalkanes.
- Keinan, E.,Perez, D.,Sahai, M.,Shvily, R.
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p. 2927 - 2938
(2007/10/02)
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- A CONVENIENT METHOD FOR THE SYNTHESIS OF DIIODO COMPOUNDS. FACILE CLEAVAGE OF CYCLIC ETHERS BY PHENYL DICHLOROPHOSPHATE AND SODIUM IODIDE
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Cyclic ethers were found to react readily with phenyl dichlorophosphate and sodium iodide to give diiodo compounds under mild reaction conditions.
- Liu, Hsing-Jang,Shewchuk, Lisa M.,Llinas-Brunet, Montse
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p. 3043 - 3046
(2007/10/02)
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- Determination of busulfan in plasma by GC-MS with selected-ion monitoring
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A GC-MS technique with selected-ion monitoring is described for the determination of busulfan in plasma. Busulfan is extracted from plasma with methylene chloride and converted to 1,4-diiodobutane. Analysis by GC-MS with selected-ion monitoring (m/z 183) gave a relative standard deviation of ± 4.3% (n = 5) at the 10-ng/ml level.
- Ehrsson,Hassan
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p. 1203 - 1205
(2007/10/02)
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