Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts. dynamic kinetic resolution

The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2-diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with high enantioselectivity. [reaction: see text]     

Separation and characterisation of caprolactam-formaldehyde reaction products

Methylolation and condensation products formed in caprolactam-formaldehyde reaction mixtures have been identified using nuclear magnetic resonance (NMR) and mass spectrometry (MS). Previously unreported side-products were also detected. All of the reaction products were separated by micellar electrokinetic chromatography (MEKC) and high performance liquid chromatography (HPLC), and the separation parameters, such as efficiency and distribution constants, obtained in the two techniques were compared. For quantification, the response factors for the monomers were determined using standard calibration and hydrolysis, whilst those for the condensation products were deduced from the values of the monomers. The accurate determination of the response factors was confirmed by checking the mass balance of a known mixture.     

Similarity search profiling reveals effects of fingerprint scaling in virtual screening

Fingerprint scaling is a method to increase the performance of similarity search calculations. It is based on the detection of bit patterns in keyed fingerprints that are signatures of specific compound classes. Application of scaling factors to consensus bits that are mostly set on emphasizes signature bit patterns during similarity searching and has been shown to improve search results for different fingerprints. Similarity search profiling has recently been introduced as a method to analyze similarity search calculations. Profiles separately monitor correctly identified hits and other detected database compounds as a function of similarity threshold values and make it possible to estimate whether virtual screening calculations can be successful or to evaluate why they fail. This similarity search profile technique has been applied here to study fingerprint scaling in detail and better understand effects that are responsible for its performance. In particular, we have focused on the qualitative and quantitative analysis of similarity search profiles under scaling conditions. Therefore, we have carried out systematic similarity search calculations for 23 biological activity classes under scaling conditions over a wide range of scaling factors in a compound database containing approximately 1.3 million molecules and monitored these calculations in similarity search profiles. Analysis of these profiles confirmed increases in hit rates as a consequence of scaling and revealed that scaling influences similarity search calculations in different ways. Based on scaled similarity search profiles, compound sets could be divided into different categories. In a number of cases, increases in search performance under scaling conditions were due to a more significant relative increase in correctly identified hits than detected false-positives. This was also consistent with the finding that preferred similarity threshold values increased due to fingerprint scaling, which was well illustrated by similarity search profiling.     

Human serum albumin-mediated stereodifferentiation in the triplet state behavior of (S)- and (R)-carprofen

A remarkable stereodifferentiation has been observed in the interaction between the excited triplet state of carprofen (CP) and human serum albumin (HSA). Time-resolved measurements using laser flash photolysis reveal the presence of two components with different lifetimes in triplet decay. This is explained by complexation of CP to the two possible HSA binding sites. The shorter-lived components are ascribed to the CP/HSA complexes in site I, where stereodifferentiation is more important (tauR/tauS ca. 4). This is correlated with formation of a dehalogenated photoproduct upon steady-state photolysis.     

Synthesis of an iminosugar based peptidomimetic analogue

The synthesis of an 1-deoxymannojirimycin based analogue of a known HIV-protease inhibitor is described. The strategies employed for introduction of the pharmacophore groups onto the azasugar scaffold were based on regioselective reactions of the hydroxyl groups of the natural product and of d-fructopyranoside derivatives.     

Enantioselective straightforward access to benzo[b]thiophene analogs of Azatoxin

Horner-Wadsworth Emmons olefination followed by asymmetric hydrogenation allowed the first synthetic access to the chiral thiotryptophan with good enantiomeric excess. Oxazolidinone formation followed by a Pictet–Spengler condensation provided the benzothiophenic analog of Azatoxin.     

Solid State NMR and TG/MS Study on the Transformation of Methyl Groups During Pyrolysis of Preceramic Precursors to SiOC Glasses

The sol-gel method was used to prepare two different starting gels containing SiCH₃-groups for the preparation of SiOC ceramics. To understand the role of Si—H bonds in the incorporation of carbon into the SiOC network, gels prepared from a 1:2 mixture of triethoxysilane and methyldiethoxysilane (T^HD^H2) and solely methyltriethoxysilane (T^Me) were investigated. Thermogravimetric analysis coupled with mass spectroscopy (TG-MS) in inert atmosphere was performed to attain an insight into the decomposition reactions involved during gel-glass transformation. Samples calcined at different temperatures up to 1000°C were characterized by ²⁹Si and ¹³C magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. The presence of SiH groups in the starting gel allows an efficient conversion of Si—CH₃ groups into CSi₄ sites at lower temperatures. As a result, despite a much lower amount of carbon in the starting T^HD^H2 gel (C/Si = 0.33) compared to the T^Me gel (C/Si = 1), the amount of carbon inserted into the SiOC network of both glasses is equivalent, but the T^Me sample contains the 10 fold amount of free carbon.     

Ferrocene incorporating host-guest dyads with electrochemically controlled three-pole hydrogen bonding properties

We describe the electrochemically controlled hydrogen bonding interactions between the isobutyl flavin/2,6-diferrocenylamidopyridine (2·5) and 9,10-phenanthrenequinone/1-ferrocenyl-3-hexylurea (4·6) dyads. Cyclic and square wave voltammetry studies have shown that the binding efficiencies between these moieties can be electrochemically actuated in non-polar (CH₂Cl₂ for 2·5) or polar (DMF for 4·6) organic solvents between three distinct states.     

Synthesis of sugar-based ethenyl ethers through a vinyl bis-sulfone methodology

The recently devised route to ethenyl ethers—i.e. 1,2-bis(phenylsulfonyl)ethylene (BPSE)-mediated conversion of alcohols into β-alkoxyvinyl sulfones followed by reductive desulfonylation—has been applied in the carbohydrate field to the synthesis of a number of vinyl-functionalised monosaccharides, a number of which had not been prepared via alternative routes.     

Hexacyanometalate molecular chemistry: di-, tri-, tetra-, hexa- and heptanuclear heterobimetallic complexes; control of nuclearity and structural anisotropy

Following a bottom-up approach to nanomaterials, we present a rational synthetic route to high-spin and anisotropic molecules based on hexacyanometalate [M(CN)(6)](3-) cores. Part 1 of this series was devoted to isotropic heptanuclear clusters; herein, we discuss the nuclearity and the structural anisotropy of nickel(II) derivatives. By changing either the stoichiometry, the nature of the terminal ligand, or the counterion, it is possible to tune the nuclearity of the polynuclear compounds and therefore to control the structural anisotropy. We present the synthesis and the characterisation by mass spectrometry, X-ray crystallography and magnetic susceptibility of bi-, tri-, tetra-, hexa- and heptanuclear species [M(CN)(n)(CN-M'L)(6-n)](m+) (with n=0-5; M=Cr(III), Co(III), M'=Ni(II); L=pentadentate ligand). Thus, with M=Cr(III), d(3), S=3/2, a dinuclear complex [Cr(III)(CN)(5)(CN-NiL(n))](9+), (L(n)=polydentate ligand) was built and characterised, showing a spin ground state, S(G)=5/2, with a ferromagnetic interaction J(Cr,Cu)=+18.5 cm(-1). With M=Co(III) (d(6), S=0) were built di-, tri-, tetra-, hexa and hepanuclear CoNi species: CoNi, CoNi(2), CoNi(3), CoNi(5) and CoNi(6). By a first approximation, they behave as one, two, three, five and six isolated nickel(II) complexes, respectively, but more accurate studies allow us to evaluate the weak antiferromagnetic coupling constant between two next-nearest neighbours M'-Co-M'.