Current Organic Chemistry - Volume 9, Issue 17, 2005

Cycloaddition and cycloisomerization reactions involving alkynes grant a rapid access to arenes, cyclic dienes, and cyclopentenone derivatives. The use of alkynes substituted by group 13 or 14 heteroelements as partners for such reactions is an emerging strategy. Indeed, the specific electronic properties of these heteroelements can play a crucial role for controlling the chemo- and regioselective outcome of a given reaction. Moreover, the heteroatoms can be considered as latent functional groups and would allow for further transformations including Suzuki-Miyaura or Stille crosscouplings. Both aspects will be presented in this review.

This review deals with the applications of the Favorskii rearrangement in synthetic Organic Chemistry, paying especial attention to the literature appeared after 1980. The mentioned rearrangement plays a key role in many total synthesis due to the fact that important modifications in the structure of the substrate occur during the process. Skeletal rearrangements in acyclic systems, leading to highly branched carboxylic acids and its derivatives, as well as structural changes in cyclic substrates, which result in ring contraction processes, are described. Some examples of Favorskii rearrangements in biosynthetic pathways are also presented.

Copper(II) salts are widely applied for the halogenation of aromatic and heteroaromatic systems, the halides. In coupling reactions, CuCl2 has been used as a catalyst for the benzylation of aromates, the synthesis of alkanes, and the preparation of diacetylenes, cyclohexenones and symmetric biaryls. It has further proved suitable for stereoselective cyclization to lactones, carbon-nitrogen coupling and lactamization, and for the simple preparation of aroylaminohydrazones, the allylic amination of olefins, the carbonylation of alkylamines, and heterocyclizations to pyrrolidinones, pyridinones, pyrroles and dihydrofurans. The dehydrogenation of carbocycles and heterocycles can be used in the synthesis of gibberelic acid, for the aromatization of oestrogen derivatives and for the conversion of dihydrouracils to uracils. From tetrahydroisoquinolines, dihydro derivatives have been formed, while dihydropyridazines in the presence of Cu(II) salts yield pyridazines. Similarly, the oxidations of cyclohexane, adamantane and methylcatechol to benzoquinone, and amines to nitriles have been performed. The conversion of aldehydes to nitriles and benzyl radical cyclizations to butyrolactones have been achieved. Protection and deprotection, and various other Cu(II) halide-mediated reactions are also discussed.

The synthesis of a substituted 2-pyridone ring is a topical area of continuing interest due to the number of biologically active molecules containing this moiety. Over the last decade, natural compounds with this structure have emerged as potent antitumor antiviral and attention, because those compounds may be studied as a simple model for investigating mechanisms of some enzymatic reactions or for discerning the behavior of nucleic acids bases in connection with mutation due to base mispairing or other mistaken helices. Recent studies have shown the usefulness of 2-pyridones as intermolecular connectors between building blocks in material science. Thus, despite the large number of methods known for their synthesis, new procedures are continuously being developed. Two main synthetic approaches can be found in the literature: from other heterocycles systems or condensation of acyclic systems. The latter can be further classified depending on the bond formed in the cyclization step: by C-C or C-N bond generation. The latter can be subclassified depending on the first condensation step. This is a review of new or improved methods for constructing 2-pyridone rings. This article will be restricted to ring formation, which can be included in the total synthesis of several compounds with specific biological or material properties. The pursuit of these properties requires efficient synthetic routes that allow rapid assembly and variation of multiple pendant substituents on the heteroaromatic case, which permits rapid analogsynthesis (RAS) [1].

In the field of molecular biology and biochemistry in which structural genomics comes as a complement to genome sequencing, Small-Angle X-ray Scattering (SAXS) is an experimental technique that, though not widely known and applied, represents a very powerful tool in the framework of post-genome structural studies. The aim of this review is to present a synthetic description of the basic principles of the theory of SAXS and to discuss in more detail its applications to the study of different biological molecules, focusing the attention to the recent advances in the structural analysis of proteins. These studies are presently undergoing a spectacular expansion associated with the development of powerful data analysis software, with the improvement of the quality of data recorded with synchrotron radiation, and finally with the increasing availability of high resolution three-dimensional structures which can constitute a starting point for the analysis of protein conformations in solution. The advantage of SAXS with respect to other techniques in the structural studies of proteins resides in the possibility of performing the measurements in any desired solvent and in the ability to follow changes of the protein structure which may occur as a response to a variety of stimuli: pH or temperature changes, interaction with small ligands, influence of substrate analogues, chemical or genetic modifications, etc. In this review we describe the principles of SAXS and the most recent methods for data analysis in the field of structural biology and, finally, we report some examples of the use of this technique as a powerful tool to the structural study of proteins in solution.