4282-42-2Relevant articles and documents
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
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
, p. 63 - 71 (2019)
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.
One-Pot Transformation of Aliphatic Carboxylic Acids into N-Alkylsuccin-imides with NIS and NCS/NaI
Nakai, Yuhta,Moriyama, Katsuhiko,Togo, Hideo
, p. 768 - 772 (2017/01/18)
Primary aliphatic carboxylic acids were treated with N-iodosuccinimide (NIS) in 1,2-dichloroethane to form the corresponding alkyl iodides under warming conditions. Based on these results, those aliphatic carboxylic acids were treated with NIS, followed by the reaction with K2CO3to give the corresponding N-alkylsuccinimides in good yields in one pot. Moreover, those aliphatic carboxylic acids were treated with N-chlorosuccinimide (NCS) and NaI, followed by the reaction with K2CO3to provide the corresponding N-alkylsuccinimides in good to moderate yields in one pot. By using the present method, successive treatment of primary aliphatic carboxylic acids (10 mmol) with NIS, K2CO3, and then hydrazine provided the corresponding decarboxylated primary amines in good yield.
Hydroalumination of alkenes by the LiAlH4*3AlBr3 system
Gorobets, E. V.,Shitikova, O. V.,Lomakina, S. I.,Tolstikov, G. A.,Kuchin, A. V.
, p. 1573 - 1578 (2007/10/02)
The hydroalumination of a series of alkenes and some fused aromatic hydrocarbons by the LiAlH4*3AlBr3 system in low-polar solvents was studied.Alkenes with mono-, di-, tri-, and tetraalkyl substituted, mono- and diaryl substituted double bonds and anthracene react at room temperature to give the corresponding dibromoaluminoalkanes in high yields.Benzylidenefluorene, tetraphenylethylene, naphthalene, and phenanthrene do not undergo hydroalumination under these conditions.Camphene, bicyclooct-2-ene, and norbornene afford the corresponding organoaluminum compounds with high stereoselectivity.Oxidation and halo- and acyldemetallation of the resulting alkyl- and arylalanes were carried out.
