Current Organic Chemistry - Volume 14, Issue 11, 2010

The aim of this review is to emphasize the importance of modified dinucleotide cap analogs and their useful biological and therapeutic applications. Dinucleoside 5'-5'-triphosphates fulfill numerous regulatory, signaling, or energetic functions (mRNA metabolism- synthesis, nucleo-cytoplasmic transport, translation, silencing, and turnover) in biological systems. In this context, we highlight the recent studies on the improvement in the design, synthesis and biological application of chemically synthesized cap analogs. The 5'- terminus of eukaryotic messenger RNA (mRNA) molecules contain a unique 'cap' structure: 7-methylguanosine (m7G) linked by a 5'-5'- triphosphate bridge to the first nucleoside in the standard polymer chain. This 5'-cap is recognized by numerous enzymes involved in the transport and translation of mRNA, as well as its processing, both in terms of generating mature mRNA from the initial transcript and its mRNA turnover. These chemically modified cap analogs are mostly anti-reverse cap analogs (ARCA) variants that result in a forward oriented cap structure after their incorporation into mRNA. The recent chemical modifications on 7-methylguanosine (m7G) either at 2' or 3' hydroxyl group with -OCH3, -fluoro, -2' or 3' deoxy G, conformationaly constrained cap modifications such as -2', 3' isopropyledene or LNA substitutions, and triphosphate bridge modifications are discussed along with their biological significance. Due to their relevance in biological processes, the 5'-capped mRNA poly(A) with modified dinucleotide analogs have attracted considerable interest in biotechnology. This review focuses on the recent development of synthetic dinucleotide cap analogs, which are widely employed as tools for studying physiological processes as well as ARCA capped mRNA's potential use in clinical applications are discussed.

Iron catalysts are extensively used in organic reactions in recent years since iron is one of the most abundant metals on earth, consequently one of the most inexpensive, and environmentally friendly ones, and many iron salts and complexes are commercially available. This comprehensive review attempts to cover the advances of iron-catalyzed organic reactions in the literature from 2007 to Sept 2009, particularly focusing on the formation of carbon-carbon bond. Simultaneously, the iron-catalyzed formation of carbon- heteroatom and heteroatom- heteroatom bond also are commented briefly.

We describe the synthesis and effect of complexation on photochemical E (trans) to Z (cis) isomerization of lariat azacrown ethers. Lariat azacrown ethers-Ca2+ complexes are characterized by UV-Vis, 1H-NMR and fluorescence techniques. Photostationary state composition of E-Z isomers upon irradiation under direct excitation and complexation with Ca(ClO4)2, quantum yield of photoisomerization, and fluorescence properties are described. Anomalous increase in the quantum yields were observed for lariat azacrown ether-Ca2+ complexes. Fluorescence studies indicated that the highly polarized/charge transfer nature of the singlet excited state is involved in E (trans) to Z (cis) isomerization process.

The [2+2+1]-cycloaddition of an alkyne, an alkene and carbon monoxide known as Pauson-Khand reaction is a powerful way to install two new functional groups and a cycle into a molecule. The great potential of this reaction has thus far been underestimated in the synthesis of pharmacologically active compounds.

In the last decades photocatalyzed organic processes have attracted the great interest, due to their low environmental impact. Various oxidation and reduction processes of organic substrates have been developed as alternative routes to the “classical” synthesis of more complex molecules. In this attempt TiO2 is actually largely studied and employed, especially as catalyst in the organic pollutants photodegradation to products with less environmental impact. From the synthetic point of view, the attention has been focused particularly on the TiO2-mediated synthesis of alcohols, carbonyl- and carboxylic- derivatives. Recently our group has developed new TiO2- photocatalyzed synthetic protocols for the functionalization of N-heteroaromatic bases as an alternative to the “classic” well known redox metal-catalyzed methods. These substrates are suitable for the nucleophilic free-radical addition and the photocatalytic activity of microcrystalline TiO2 has shown a key role in the success of our protocol.