Current Organic Chemistry - Volume 12, Issue 5, 2008

This issue constitutes Part II of the thematic issue of Bioorganic Chemistry. It contains two timely reviews that highlight backbone modifications in oligonucleotides and peptides. The first of them, contributed by Jung and Marx, compiles the synthetic studies of 4'-substituted nucleosides and their incorporation into oligonucleotides. These structural modifications have gained interest for the reason that they may protect the oligonucleotide backbone toward enzymatic degradation and simultaneously allow introduction of conjugate groups in a manner that does not hamper hybridization. Accordingly, the physico-chemical properties of the oligonucleotide may conveniently be tuned by 4'-substitution. The review by Deska and Kazmaier, in turn, concerns backbone modifications of peptides. While human proteins and peptides are composed almost exclusively of 20 common L-amino acids, the amino acid content of peptide-based secondary metabolites of lower organisms is much more versatile, and many of such abnormal peptide structures exhibit pharmacological properties. For this reason, and to obtain appropriate chemical models for structural motives of proteins, synthesis of backbone modified peptide has received wide interest. The results of these synthetic efforts are compiled. I thank the contributors for their thorough work. Hopefully many of the readers of Current Organic Chemistry will find these reviews interesting.

4'-C-Modified nucleotides and oligonucleotides have been explored extensively recently. The motivations for these investigations drive from the development of new drugs to investigations of complex biological processes. This review covers the common strategies for the synthesis of 4'-C-modified nucleosides that have been subsequently incorporated into oligonucleotides. After a brief depiction of two mainly followed routes for the generation of 4'-C-modified nucleosides, the synthetic efforts of the modified nucleotides are grouped into those bearing hydrophobic or polar modifications. Subsequently strategies for the incorporation of the respective nucleotides into oligonucleotides by automated DNA synthesis are discussed.

The selective introduction or manipulation of side chains in a peptide represents a severe synthetic challenge. During the last years numerous different approaches towards the targeted modification of small to medium-sized peptides have been developed which should be presented in this review. Focusing on the manipulation of the peptide backbone, procedures concerning selective N-alkylation, C-alkylation and Cequals;O-thionation are described.

In the past two decades, chiral sulfoxides have been finding increasing use, reflecting growing interest both in convenient auxiliaries in asymmetric synthesis and products with biological properties containing a chiral sulfinyl group. In 1984, groups of Kagan and Modena discovered that titanium(IV) isopropoxide - diethyltartrate based systems (also known as “modified Katsuki-Sharpless reagents”) are capable of asymmetric oxidizing of prochiral sulfides by alkylhydroperoxides. Later, catalytic versions of the titanium tartrate systems were developed (with up to 90 % yield and 90 % ee for certain sulfides) that remain the most applied systems for asymmetric sulfoxidations. However, the low turnover numbers (5-20), complexity and expensiveness of such systems stimulated the search for other transition metal based catalytic systems. This review will cover the progress in transition metal catalyzed asymmetric sulfides oxidations achieved since the discoveries of early 1980s to the present days.

Transition metal-catalyzed addition of a mono- and a diboron reagent to unsaturated carbon-carbon bonds provides an efficient and convenient route for the preparation of mono- and diboronic compounds. These compounds are versatile intermediates for the purposes of organic synthesis. Catalytic control of the chemo-, regio- and diastereoselective CB formation enables access to highly selective functionalized molecules by consecutive tandem sequences. Mechanistic insights involving concatenated reactions through boron chemistry are reviewed and discussed with particular emphasis on the role of the catalytic systems, the scope of the substrates and reagents, and the origin of the asymmetric induction. Recent developments in the cascade reaction from borylation or the formation of carbocycles via multiple carborhodation steps triggered by the rhodium-catalyzed intermolecular addition of organoboron are not covered, however, since they have been the object of other reviews [1].

One of the most important subjects in contemporary proteomics is the relative and absolute quantification of gene expression at the protein level. The application of stable-isotope coded tagging in conjunction with high performance bioanalytical methods such as liquid chromatography and mass spectrometry for the separation and identification of proteins and peptides has proven successful to reveal global changes in protein expression in both comparative and absolute manners. The rapid progress in the field is evidenced by the introduction of quite a few stable isotope labeled novel reagents for protein and peptide tagging with particular structural characteristics. In this review we focus on the chemical design, structure and synthesis of the most important of such tagging reagents, also addressing their advantages and limitations in quantitative proteomics.