Current Organic Chemistry - Volume 16, Issue 20, 2012

The scope of this account on addition reactions in aqueous media is to demonstrate that the syntheses of useful targets or functionalizations can be accomplished through photoaddition reactions in benign environments. Ammination reactions of olefins and constrained cycloalkanes, addition products derived from quinonemethides, aromatic arylation reactions of furanones and alkenes, and radical addition reactions to α,β-unsaturated aldehydes performed in aqueous media constitute valuable reactions and hence interesting synthetic targets in organic syntheses. In studying these synthetic targets, different light sources are employed to achieve excitation. Also, photoinduced electron transfer sequences will account for the addition products. This account does exclude the photoaddition reactions performed by the aid of metals or metallic complexes, or the addition of perfluoroalkyl radicals to carbon-carbon and carbon-heteroatom multiple bonds in aqueous media.

Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed with particular focus on oral drug administration. This article focuses on development of in vitro reliable and simple prototypes for oral drug delivery by combing chemical, structural and pharmacological knowledge available to date in order to create an optimal oral drug delivery system based on modified cyclodextrins. Practical in vitro model is also demonstrated.

This account intends to cover recent literature on photoinduced cyclization reactions in water or aqueous media. The reactions covered do not proceed by the assistance of metals, or through electron transfer reactions mediated by metallic species or complexes. Radical cyclization of perfluoroalkyl-substituted compounds is neither the subject of this article, since these examples have been reviewed recently. Instead, photomacrocyclization and photoelectrocyclic ring closure reactions are the aims of this article, as well as the syntheses of lactones and 5-methyleneoxazolidin-4-ones, showing the scope of these reactions carried out in an environmentally-friendly media. These cyclization reactions will be shown to enable the syntheses of important synthetic targets, with relevancy in biochemistry and medicinal chemistry.

This review deal with the reactivity of 5-substituted uracil derivatives toward peroxyl radicals. These compounds should play an important role in biological systems and have considerable attention in pharmacology. Comparative evaluation of reactivity is carried out, as well as methodologies studies for the reactivity of uracil derivatives toward peroxyl radicals were also discussed. Structurereactivity relationship will be considered on 15 derivatives using theoretical and experimental data. Reaction mechanism will be analyzed in the framework of several categories e.g. additions with formation of less reactive radical, electron transfer reaction and H-atom abstraction.

This account intends to cover recent literature on photoinduced substitution reactions in water or aqueous media with synthetic utility. Interesting synthetic targets, such as benzothiazine rings, benzoxazoles, aromatic photosubstitutions on 6-fluoroquinoles, can be accomplished in a benign aqueous environment, reducing the impact of organic solvents, or the use of metals for substitution reactions. Synthetically-useful electron-transfer substitution reactions performed in aqueous media are noteworthy and not much developed. These reactions performed either through radicals or radical ion intermediates generated photochemically in aqueous environment will prove convenient and alternative sustainable options at hand for the organic synthetic chemist. Metal-mediated photoinduced electron transfer reactions will not be dealt with in this account, as have been the subject of recent review articles, as is the case of radical perfluoroalkylation substitution reactions in aqueous media which have been recently summarized.

Over the last few decades decatungstate-mediated reactions have been explored extensively and have found widespread applications in catalysis. In particular, decatungstate has been successfully used as an efficient catalyst in many oxidative chemical transformations, via free radical pathways, and to a lesser extent under anaerobic conditions in synthetically useful chemical processes. In view of its unique photocatalytic properties, decatungstate (W10O32 4-) is rapidly emerging as a promising tool in organic chemistry. This review deals with the recent developments in the chemistry of decatungstate, including mostly synthetic and mechanistic aspects. Several representative examples that illustrate the diverse uses of decatungstate in organic synthesis via free radical carbon centered intermediates in organic and in aqueous media are presented. Thus, the decatungstate-mediated radical functionalization of several classes of organic compounds such as alkanes, alkenes, alcohols, aldehydes and sulfides, under both aerobic and anaerobic conditions, represents a reaction of fundamental and practical interest in academia and industry. Several new discoveries concerning the heterogenization of decatungstate for the development of sustainable methods with broad applications in catalysis, such as the photooxidation or photodegradation of various organic substrates, are also presented.

The open porous materials (PolyHIPEs) based on high internal phase emulsions (HIPEs) stabilized by copolymer particles had been prepared through adding small quantity (about 0.5 wt% relative to the external phase) of cationic surfactant, cetyltrimethylammonium bromide (CTAB), into the oil (external) phase. The effect of copolymer particle concentration, surfactant concentration and CTAB position in HIPEs on the morphologies of PolyHIPEs was investigated. All these factors could tune the internal structures of the Poly- HIPEs and some of them generated pore throats on the pore wall. Obvious synergistic interaction between the negative-charged particles and cationic surfactant CTAB in HIPE was displayed: CTAB could not only adsorb on the oil-water interface competitively with the copolymer particles but also cross the interface to absorb on the particle surface, which changed the particle hydrophilicity. The further investigation on the stability of HIPE proved that the HIPEs with CTAB in the oil phase were more prone to form open porous materials after polymerizing the monomer in the external phase.

Sodium thiomethoxide and dimethyldisulfide will be shown to be convenient sources of methyl thiyl radicals for effecting the cis-trans double bond isomerization of oleic acid to elaidic acid residues arranged in phospholipid bilayers of the microheterogeneous aqueous environment of liposomes. The methods used for methyl thiyl radical generation encompass radiolytic and photochemical methods. The convenience of these methyl thiyl radical sources will be interpreted in terms of the turn-over numbers in the radical chain cistrans isomerization reaction of unsaturated lipids.

Oral mucositis is a consequence of the toxic effects of chemotherapeutic agents and irradiation on oral mucosa cells. It is estimated that oral mucositis is a complication in 40% of patients receiving chemotherapy, more than 90% of those irradiated for head and neck cancer. This condition is frequently associated with severe pain and inflammation and can cause malnutrition, systemic infections, and low quality of life, as well as limiting chemotherapy doses. The pineal hormone melatonin inhibits the production of free radicals that mediate the toxicity of chemotherapy. The main objectives of this study is to develop and evaluate a novel occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis based on chitosan and melatonin in order to exploit natural biomaterials as functional biocompatible gels and evaluate the performance of the alternative drug delivery system towards in-vitro generated free-radical mediated inflammation response as a model system for oral mucosatis.

We recently showed that chitosan containing hydrogel isare capable of displaying antioxidant activity and prevents formation of oxidative DNA damage in vitro [9]. In this short communication we report our investigations towards developing two alternative novel simple flexible and effective drug delivery systems that provide optimal dosage of drugs precisely where and when needed and therefore achieve and sustain a complex delivery profile. Two topics of a. free radical generation in biocompatible media and b. supramolecular host-guest recognition through miniaturizing and multi-functionalizing molecular carriers for improved drug delivery in disease-specific manner are combined with the aim of harnessing free radical reactivity within the laboratory and developing alternative and effective treatments for disease states mediated by free radicals.

In the past decade, the organocatalytic asymmetric Michael addition has emerged as one of the most important carbon-carbon bond forming reactions in organic chemistry. As an example, the conjugated addition of ketones to nitroolefins has received extensive attention, since the resulting nitroalkanes are versatile intermediates in which the nitro group can be transformed into various useful functional groups. Furthermore, the reaction has the ability to introduce two vicinal stereogenic centers in a single step. Stimulated by the seminal work of List, Barbas and coworkers, several research groups have focused on the development of novel bifunctional organocatalysts bearing amine and hydrogen donor functionalities. This review will focus on the development of multifunctional chiral organocatalysts derived from proline, pyrrolidine, cinchona alkaloids, thioureas and sulfonamides in the asymmetric Michael addition to nitroalkenes.

The review article covers the hypervalent organoantimony compounds that are with intramolecular N, O, S→Sb coordinations synthesized in the past 20 years. We describe their structures and the related coordination chemistry, highlighting a number of hypervalent stibines. These compounds have shown many applications in organic synthesis. They are useful reagents for reactions such as crosscoupling and arylation with organic halides, and addition with carbonyl compounds. They can be used as Lewis acid catalysts in organic synthesis. Furthermore, they can be utilized as catalysts or reagents for CO2 chemical fixation. It is envisaged that more hypervalent organoantimony compounds of novel structure will be synthesized and find new applications in the near future.

Highly dispersed copper iodide on activated carbon (CuI/C) solid catalyst has been investigated for the Paal–Knorr condensation of γ-diketones with aliphatic, aromatic and heterocyclic amines under solvent-free conditions; which lead to the formation of N- substituted pyrrole derivatives in excellent yields. This simple experimental procedure combined with easy recovery and reusability of the catalyst is expected to contribute to the progression of a clean and ecofriendly strategy for the synthesis of N-substituted pyrrole derivatives.