Ileana Dragutan

Targeted drugs by olefin metathesis: piperidine-based iminosugars

Examining advances in the class of natural and non-natural piperidine azasugars, important therapeutic agents and potent glycosidase inhibitors, this review looks at syntheses applying olefin metathesis as a highly efficient key step and gateway strategy for discovery of better iminosugar leads for treatment of widespread affections like viral and metabolic diseases. Amply illustrated is how ring-closing metathesis (RCM and RCEYM), promoted by commercial ruthenium alkylidene catalysts, manage to construct the common tetrahydropyridine core while cross-metathesis (CM), starting from this generic scaffold, provides general access to families of novel azasugars. Special consideration is given to high-profile iminosugar drugs of this class (1-deoxynojirimycin and congeners, adenophorine, fagomine, isofagomine and some of their N- and C-substituted analogues) stressing upon newest trends for enhancing biological activity and modulating previously unexploited targets in multispecific therapies.

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

Summary By focusing on recent developments on natural and non-natural azasugars (iminocyclitols), this review bolsters the case for the role of olefin metathesis reactions (RCM, CM) as key transformations in the multistep syntheses of pyrrolidine-, piperidine- and azepane-based iminocyclitols, as important therapeutic agents against a range of common diseases and as tools for studying metabolic disorders. Considerable improvements brought about by introduction of one or more metathesis steps are outlined, with emphasis on the exquisite steric control and atom-economical outcome of the overall process. The comparative performance of several established metathesis catalysts is also highlighted.

Ruthenium Complexes Bearing N-Heterocyclic Carbene (NHC) Ligands

A review of recently published aspects on ruthenium complexes with nucleophilic N-heterocyclic carbene (NHC) ligands is presented here, in continuation of a paper published in the July issue of this Journal, that covered initial work and subsequent main developments in this chemistry. In Part II selected applications of these complexes as pre-catalysts in metathesis reactions are highlighted. Particular attention is paid to metathesis in room temperature ionic liquids as the solvents, asymmetric catalysis, and in situ generated, very active catalytic systems based on NHC-platinum group metals. Most NHC-platinum group metal complexes are useful as highly active and selective pre-catalysts for fundamental chemical transformations.

Rational design and convenient synthesis of a novel family of ruthenium complexes with O,N-bidentate ligands

A two step procedure for the synthesis of a novel family of homogeneous and immobilized Ru-complexes containing Schiff bases as O,N-bidentate ligands is described. The new Ru-complexes have been structurally characterized by IR, Raman,1H-,13C-NMR spectroscopy. The Schiff bases were associated with a diversity of inorganic and organic ligands such as chloride, phosphane, arenes, various carbenes (alkylidene, vinylidene, indenylidene and allenylidene as well as N-heterocyclic carbenes) and cyclodienes. By choosing a selective range of substituents for the Schiff base, useful physical and chemical properties of the prepared Rucomplexes can be induced. This synthetic approach is promising in creating a valuable and diverse selection of Ru-complexes, valuable for future applications.

Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes

Recent trends in Ru complex chemistry are surveyed with emphasis on the development of anticancer drugs and applications in catalysis, polymers, materials science and nanotechnology.

Modulation of Oxidative Damage by Nitroxide Free Radicals

Piperidine nitroxides like 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) are persistent free radicals in non-acidic aqueous solutions and organic solvents that may have value as therapeutic agents in medicine. In biological environments, they undergo mostly reduction to stable hydroxylamines but can also undergo oxidation to reactive oxoammonium compounds. Reactions of the oxoammonium derivatives could have adverse consequences including chemical modification of vital macromolecules and deleterious effects on cell signaling. An examination of their reactivity in aqueous solution has shown that oxoammonium compounds can oxidize almost any organic as well as many inorganic molecules found in biological systems. Many of these reactions appear to be one-electron transfers that reduce the oxoammonium to the corresponding nitroxide species, in contrast to a prevalence of two-electron reductions of oxoammonium in organic solvents. Amino acids, alcohols, aldehydes, phospholipids, hydrogen peroxide, other nitroxides, hydroxylamines, phenols and certain transition metal ions and their complexes are among reductants of oxoammonium, causing conversion of this species to the paramagnetic nitroxide. On the other hand, thiols and oxoammonium yield products that cannot be detected by ESR even under conditions that would oxidize hydroxylamines to nitroxides. These products may include hindered secondary amines, sulfoxamides and sulfonamides. Thiol oxidation products other than disulfides cannot be restored to thiols by common enzymatic reduction pathways. Such products may also play a role in cell signaling events related to oxidative stress. Adverse consequences of the reactions of oxoammonium compounds may partially offset the putative beneficial effects of nitroxides in some therapeutic settings.

Ruthenium Complexes Containing Bidentate Schiff Base Ligands as Precursors of Homogeneous and Immobilized Catalysts

The paper presents recent work conducted in our group on the synthesis of a novel class of homogeneous and immobilized Ru- complexes containing Schiff bases as O,N-bidentate ligands benefiting from a versatile, quite general and thoroughly exemplified two- step procedure. The new Ru-complexes with improved stability incorporate a variety of Schiff bases, associated with traditional inorganic and organic ligands such as chloride, phosphanes, arenes, cyclodienes, NHC etc., and different carbenes (alkylidene, vinylidene, allenylidene and indenylidene). By a proper choice of the Schiff base, useful physical and chemical properties of the derived Ru- complexes could be induced resulting in tunable catalytic activity for metathesis and related processes. A pertinent example is the latency of selected Schiff base Ru catalysts which by becoming active only under specific conditions (heat or acid activation) are ideal for industrial applications, e.g. reaction injection molding processes. The synthetic approaches that are critically discussed in this artcile have led to a diversity of Ru-complexes of which several members have risen to the rank of commercial catalysts.

ROMP Synthesis of Iron-Containing Organometallic Polymers

The paper overviews iron-containing polymers prepared by controlled “living” ring-opening metathesis polymerization (ROMP). Developments in the design and synthesis of this class of organometallic polymers are highlighted, pinpointing methodologies and newest trends in advanced applications of hybrid materials based on polymers functionalized with iron motifs.

Practical New Strategies for Immobilising Ruthenium Alkylidene Complexes: Part II

Base Ligand Detailed studies by Verpoort et al. (2–5) have been directed towards the design, synthesis and progressive development of homogeneous and immobilised N,O-bidentate ruthenium complexes bearing Schiff base ancillary ligands, as an attractive alternative to N-heterocyclic carbenes (NHCs) (6–15) for applications in ring-closing metathesis (RCM), Kharasch addition, ring-opening metathesis polymerisation (ROMP), atom transfer radical polymerisation (ATRP) and vinylation reactions (16, 17). Structurally robust and effective supported catalysts have been devised (for example, 32–34) in which the homogeneous Ru complex was anchored to the carrier by a non-labile tether, bound to the Schiff base ligand yet imposing little or no steric hindrance at the reactive site (18–20) (Scheme I). (Structures 1–31 are given in Part I (1).) From all potential inorganic supports, the mesoporous silica gel MCM-41 (mobile crystalline material) was selected as most appropriate because of its advantages (21–24): (i) retention of a constant exposed surface area, in contrast to conventional polymer beads that typically swell and shrink variably in different media, resulting in unpredictable effects on the catalyst activity; (ii) the greater robustness of MCM-41 than organic

Recent advances in metathesis-derived polymers containing transition metals in the side chain

Summary This account critically surveys the field of side-chain transition metal-containing polymers as prepared by controlled living ring-opening metathesis polymerization (ROMP) of the respective metal-incorporating monomers. Ferrocene- and other metallocene-modified polymers, macromolecules including metal-carbonyl complexes, polymers tethering early or late transition metal complexes, etc. are herein discussed. Recent advances in the design and syntheses reported mainly during the last three years are highlighted, with special emphasis on new trends for superior applications of these hybrid materials.