Design, Synthesis, and Testing of a Molecular Truck for Colonic Delivery of 5-Aminosalicylic Acid

A molecular scaffold bearing eight terminal alkyne groups was synthesized from sucrose. Eight copies of an azide-terminated, azo-linked precursor to 5-aminosalicylic acid were attached to the scaffold via copper(I)-catalyzed azide–alkyne cycloaddition. The resulting compound was evaluated in a DSS model of colitis in BALB/c mice against sulfasalazine as a control. Two independent studies verified that the novel pro-drug, administered in a dose calculated to result in an equimolar 5-ASA yield, outperformed sulfasalazine in terms of protection from mucosal inflammation and T cell activation. A separate study established that 5-ASA appeared in feces produced 24–48 h following administration of the pro-drug. Thus, a new, orally administered pro-drug form of 5-aminosalicylic acid has been developed and successfully demonstrated

Lewis acid catalysis in organic synthesis

Gadolinium triflate (Gd(OTf)₃) was found to be a simple and efficient catalyst for the acetylation of alcohols and amines in both conventional organic solvents and as well as in room temperature ionic liquids (TRIL). Acetylation reactions using acetic anhydride as the reagent proceed in excellent yields, in the presence of catalytic amounts (0.01 - 0.5 mol %) of Gd(OTf)₃, at ambient temperature. Acetylations of variety of aliphatic alcohols as well as phenols and amines were proceeded under mild conditions...A novel and efficient catalytic system has been developed for 1,3-dipolar cycloaddition of azides to terminal alkynes using CuCl-RTIL. This catalytical system gives only 1,4-disubstituted 1,2,3-triazoles. Reactions of Alkyl and aryl azides with a variety of terminal alkynes were successfully catalyzed using CuCl-RTIL catalytic system. This catalytic system has the additional characteristics includes simple product isolation, insensitivity to air and moisture, and tolerance to broad range of functional groups --Abstract, page iii

Synthetic Approaches to Gem-difluoromethylene Compounds

Organic compounds containing a gem-difluoromethylene group are useful for a variety of applications in biological, pharmaceutical and materials chemistry. Over the years a variety of synthetic protocols for this class of compounds have been developed. They can be prepared from their corresponding carbonyl compounds or through various derivatives such as oximes and dithiolanes, electrophilic fluorinations of unsaturated compounds and enolates, free-radical additions of halodifluoroalkanes to olefins, and nucleophilic difluoromethylations of aldehydes and ketones. Other approaches involve methods that utilize fluorinated compounds as synthons. Enantioselective gemdifluorination reactions have emerged employing chiral auxiliaries such as sulfinimines, and chiral Lewis acid catalysts. This review focuses on the recent developments in this area, emphasizing the synthetic methods that can be conveniently carried out and are potentially broadly applicable

Gadolinium Triflate: An Efficient and Convenient Catalyst for Acetylation of Alcohols and Amines

Gadolinium triflate (Gd(OTf) 3) was found to be a simple and efficient catalyst for the acetylation of alcohols and amines. Acetylation reactions using acetic anhydride as the reagent proceed in excellent yields, in the presence of catalytic amounts (0.01-0.1 mol%) of Gd(OTf) 3, at ambient temperature. Aliphatic alcohols as well as phenols and amines undergo acetylations under mild conditions. The intermediate formation of the mixed anhydride, acetic trifluoromethanesulfonic anhydride was demonstrated by 13C NMR spectroscopy experiments

Imidazolium-Based Polymer Supported Gadolinium Triflate as a Heterogeneous Recyclable Lewis Acid Catalyst for Michael Additions

A heterogeneous Lewis acid catalytic system has been developed by incorporating gadolinium triflate on to poly[styrene-co-(1-((4-vinylphenyl)methyl)-3-methylimidazolium) tetrafluoroborate] (1-Gd(OTf)3), and the catalytic activity of this system has been examined for Michael additions of amines and thiols to α,ß-unsaturated esters and acrylonitrile. The reactions proceed in moderate to excellent yields in the presence of catalytic system 1-Gd(OTf)3. The catalytic system could be efficiently recycled and reused

Gadolinium Triflate Immobilized in Imidazolium Based Ionic Liquids: A Recyclable Catalyst and Green Solvent for Acetylation of Alcohols and Amines

Gadolinium triflate immobilized in room temperature ionic liquids (RTIL) 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) was found to be a recyclable and green catalyst for acetylation of a variety of alcohols, phenols and amines. Acetylation reactions using acetic anhydride (Ac2O) as the reagent proceeded in excellent yields in the presence of catalytic amounts (0.2-0.5 mol%) of Gd(OTf)3 immobilized in RTILs, at ambient temperature. In addition, the catalyst system Gd(OTf) 3/[bmim][X] can be recovered and reused efficiently in these transformations

Gem-Difluorination of 2,2-diaryl-1,3-dithiolanes by Selectfluor® and Pyridinium Polyhydrogen Fluoride

2,2-Diaryl-1,3-dithiolanes, readily obtainable from diaryl ketones, were transformed into the corresponding gem-difluoro compounds using a novel reagent combination involving SelectfluorH and pyridinium polyhydrogen fluoride (PPHF) under mild conditions in moderate to good yields