Recent studies concerning synthesis and properties of artificial oligonucleotides containing novel nucleoside analogs with cationic alkyl side chains have been comprehensively reviewed in relation to the antisense and siRNA strategies. Synthesis of 4′-C-aminoalkyl-2′-O-methyluridines, 4′-C-aminoethyl-2′-fluorouridine, 4′-C-guanidinomethyl-2′-O-methyluridine, 4′-C-aminomethyl-2′-fluoroarabinothymidine, 5′-C-aminoalkyl-2′-O-methyluridines, 5′-C-aminopropylthymidine and 5′-C-aminopropyl-2′-fluoroarabinothymidine is described. Thermal stabilities of the oligonucleotides incorporating these nucleoside analogs have been compared. Stabilities of these oligonucleotides in a buffer containing bovine serum and abilities of the modified oligonucleotides to elicit RNase H activity are also discussed. In addition, this review deals with silencing abilities of siRNAs incorporating these nucleoside analogs.
Cyclometalated iridium(III) (Ir(III) complexes (e.g.: fac-Ir(tolpy)3 (tolpy=2-(4’-tolyl)pyridine), fac-Ir(ppy)3 (ppy=2-phenylpyridine) are extremely stable in water and organic solvents and are used as organic light emission diodes (OLEDs) and cell imaging materials due to its high emission properties. In the syntheses of various cyclometalated metal complexes, appropriate ligands are prepared and then used for the complexation with metal salts. Therefore, it is generally difficult to synthesize various metal complexes that contain labile and/or unstable functional groups under harsh reaction conditions (such as high temperature). In this review, we describe regioselective substitution reactions and successive conversions of the cyclometalated Ir(III) complexes to many derivatives for the synthesis of the functionalized Ir(III) complexes such as Ir complex-peptide hybrids (IPHs), Ir complex-chromophore hybrids (ICHs), which is called “post-complexation functionalization”, and their application to biomedical and material sciences. The synthesis of heteroleptic triscyclometalated Ir complexes via Zn2+-promoted degradation reactions is also described.
Enantioselective hydrogenations of arenes, including heteroarenes, will offer a fruitful methodology for creating stereogenic centers on chiral 5- or 6-membered rings. The resulting chiral cyclic structures are frequently seen in useful biologically active compounds. However, the asymmetric hydrogenation of arenes, particularly benzene ring, is a formidable target in synthetic organic chemistry, because the unsaturated bonds in arenes are highly stabilized with their own aromaticity. This account describes our study on the hydrogenations with asymmetric catalysis of heteroarenes and carbocyclic arenes. Previously, we had accounted the highly enantioselective hydrogenation of indoles with the chiral PhTRAP-rhodium and ruthenium catalyst. Here, we found that the chiral ruthenium catalyst is useful for the asymmetric hydrogenation of various 5-membered nitrogen-containing heteroarenes, such as pyrroles, imidazoles, oxazoles, and azaindoles. Furthermore, some fused carbocyclic arenes can be transformed into the chiral cyclohexanes with good enantiomeric excesses through the PhTRAP-ruthenium catalyst. Although the ruthenium complex failed to catalyze the hydrogenations of pyrimidines and isoxazoles, these heteroarenes were converted to the corresponding chiral heterocycles with high enantiopurities through chiral iridium catalyses.
The selective formation of linear hydrocarbon chains from C1 monomers is the most intriguing part of the Fischer-Tropsch (FT) reaction. This process has been proposed to involve surface-bound metal carbide, methylidyne, and methylene species as the pertinent monomers and different types of surface hydrocarbyl groups as possible propagating groups. Previous studies on the coupling reactions of these C1 units on homogeneous organometallic systems produced only non-propagating C-C coupling events, leaving the chain propagation models extremely elusive. We have been investigating the chemistry of ruthenium carbide complexes derived from the coordinatively unsaturated dinuclear ruthenium methylene complex [(Cp*Ru)2(µ-NPh)(µ-CH2)] (Cp*=η5-C5Me5). Herein we describe (i) the synthesis of the dinuclear bridging carbide complex [(Cp*Ru)2(µ-NPh)(µ-C)] and (ii) its use for the development of the first homogeneous model of the chain propagation step of the FT reaction. This model reaction is initiated by a C+CH2 coupling and propagates via a consecutive C=CHR+CH2 coupling and hydrogen shifts to form linear C=CH(CH2)nH chains.
Carbon dioxide (CO2) is not only a greenhouse gas but also a renewable C1 source that is important for organic synthesis. On the other hand, minimizing organic solvent is also an important subject from the viewpoint of fossil fuel, energy, resource, cost, safety, and environment. Here we summarize our achievements in solvent-free catalysis. We developed a series of bifunctional metalloporphyrin catalysts for the synthesis of cyclic carbonates or polycarbonates from epoxides and CO2. As a result of structural optimizations, Mg and Zn porphyrins having quaternary ammonium bromide groups were suitable for the synthesis of cyclic carbonates (TOF＝12,000—46,000 h−1, TON＝55,000—310,000). In contrast, bifunctional Al porphyrins were highly active for the copolymerization of cyclohexene oxide and CO2 to give polycarbonates. The solvent-free reaction with a catalyst loading of 0.0025 mol% under CO2 (2 MPa) was conducted at 120 °C for 1 h to give poly(cyclohexene carbonate): TOF＝10,000 h−1, polycarbonate selectivity >99%, PDI＝1.02, and Mn＝68,000. The reaction with a catalyst loading of 0.001 mol% for 24 h gave polymers with a Mn of 281,000, which corresponded to 2,000-mer. The high catalytic activities resulted from the cooperative action of the central metal ion and the quaternary ammonium salts. Chiral catalysts for the kinetic resolution of terminal or internal epoxides with CO2 were also developed. In addition, a BINOL derivative (L) was designed to make dinuclear metal complexes (M2L); unexpectedly, heating a mixture of M and L furnished macrocyclic multinuclear metal complexes such as Zn5L3 in high yields, which showed catalytic activities for the temperature-dependent N-formylation/N-methylation of amines with CO2 and hydrosilane. On the other hand, tetrabutylammonium acetate catalyzed the solvent-free N-formylation of amines with CO2 and hydrosilane to give formamides including Weinreb formamide, Me(MeO)NCHO, which was successively converted into aldehydes by one-pot reactions with Grignard reagents. In addition, the intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) under solvent-free conditions, and the solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently. In some cases, even solid-to-solid conversions took place.
The molecules containing a chiral sulfur center such as chiral sulfoxides are used as a toolbox for the synthesis of chiral compounds. Although the stereoselective reactions using chiral sulfur groups as a chiral directing group have been developed, the chirality transfer reactions arising from a sulfur atom have been less reported. In this short review, the recent advances in the development of chirality transfer from a sulfur to a carbon stereocenter via rearrangement reactions will be described.