Development of a new dimeric cyclophane ligand: application to enhanced diastereo- and enantioselectivity in the catalytic synthesis of beta-lactams

We detail the synthesis of a new C(2)-symmetric bis(cyclophane) ligand system that can be thought of as electronically analogous to binol, but which possesses the added "third dimension" of cyclophane chirality. The ligand synthesis involves a spontaneous (but unexpected) atropisomerization to the desired product. We have employed this ligand to form a metal complex that is an effective cocatalyst for the highly enantio- and diastereoselective catalytic asymmetric synthesis of a beta-lactam.     

Detailed product analysis during low- and intermediate-temperature oxidation of ethylcyclohexane

An experimental study of the oxidation of ethylcyclohexane has been performed in a jet-stirred reactor with online gas chromatography, under quasi-atmospheric pressure (800 Torr), at temperatures ranging from 500 to 1100 K (low- and intermediate-temperature zone including the negative temperature coefficient area), at a residence time of 2 s, and for three equivalence ratios (0.25, 1, and 2). Ethylcyclohexane displays important low-temperature reactivity with a well-marked negative temperature coefficient behavior. In addition to 47 products with a mass lower than ethylcyclohexane which have been quantified, many species with a C(8)H(14)O formula (molecular weight of 126) were detected by GC-MS and 7 of them were quantified. These molecules are cyclic ethers, ketones, and aldehydes with the same carbon skeleton as the reactant. Experiments were also carried on under the same conditions for two other C(8) hydrocarbons, n-octane and 1-octene, showing that the reactivity of ethylcyclohexane is close to that of the alkene and lower than that of the alkane. Simulations using a detailed kinetic model of the literature allow a good prediction of the global reactivity and of the main hydrocarbon products for temperatures above 800 K. The main reaction channels leading to the observed reaction products at both low (below 800 K) and intermediate temperature (above 800 K) are discussed.     

KO(t)Bu mediated synthesis of phenanthridinones and dibenzoazepinones

Synthesis of substituted phenanthridinones and dibenzoazepinones has been realized from 2-halo-benzamides in the presence of potassium tert-butoxide and a catalytic amount of 1,10-phenanthroline or AIBN. This new carbon-carbon bond forming reaction gives direct access to various biaryl lactams containing six- and seven-membered rings chemoselectively. Carbon-carbon coupling seems to proceed by the generation of a radical in the amide ring which leads to C-H arylation of aniline.     

Spectroscopic and Electrochemical Study of the Interconversion and Decomplexation of Cobalt(II) Sandwich Polyoxometalates Based on a Dawson-Type Anion

The reaction of the trivacant Dawson polyoxometalate α-[P(2)W(15)O(56)](12-) and the divalent cations Co(2+) is known to form a symmetrically derived sandwich complex of formula ββ-[Co(4)(H(2)O)(2)(P(2)W(15)O(56))(2)](16-) [symbolized as ββ-Co(4)(P(2)W(15))(2)] at low pH (ca. pH 3). We have shown previously that, by a slight modification of the reaction conditions, trinuclear αβ-[(NaOH(2))Co(3)(H(2)O)(P(2)W(15)O(56))(2)](17-) and dinuclear [(NaOH(2))(2)Co(2)(P(2)W(15)O(56))(2)](18-) complexes [symbolized as αβ-NaCo(3)(P(2)W(15))(2) and Na(2)Co(2)(P(2)W(15))(2), respectively] can be synthesized as aqueous-soluble sodium salts. αβ-NaCo(3)(P(2)W(15))(2) is a "lacunary" sandwich complex that can add a Co(2+) cation to form nearly quantitatively an unsymmetrical Dawson tetracobalt sandwich polyoxometalate, αβ-[Co(4)(H(2)O)(2)(P(2)W(15)O(56))(2)](16-) [symbolized as αβ-Co(4)(P(2)W(15))(2)]. Thus, for Co(4)(P(2)W(15))(2), the junctions between the trivacant {P(2)W(15)} subunits and the central tetrameric unit can be either both β type or β and α types. The interconversion between αβ-Co(4)(P(2)W(15))(2) and ββ-Co(4)(P(2)W(15))(2) and the decomplexation process at low pH, leading to the formation of αβ-NaCo(3)(P(2)W(15))(2) and/or Na(2)Co(2)(P(2)W(15))(2), have been followed in aqueous solution at various pH values by electrochemistry, UV-visible absorption spectroscopy, and (31)P NMR spectroscopy.     

Photoelectron spectra of some antibiotic building blocks: 2-azetidinone and thiazolidine-carboxylic Acid

X-ray photoelectron spectra of the core and valence levels of the fundamental building blocks of β-lactam antibiotics have been investigated and compared with theoretical calculations. The spectra of the compounds 2-azetidinone and the 2- and 4-isomers of thiazolidine-carboxylic acid are interpreted in the light of theoretical calculations. The spectra of the two isomers of thiazolidine-carboxylic acid are rather similar, as expected, but show clear effects due to isomerization. Both isomers are analogues of proline, which is well-known to populate several low energy conformers in the gas phase. We have investigated the low energy conformers of thiazolidine-4-carboxylic acid theoretically in more detail and find some spectroscopic evidence that multiple conformers may be present. The measured valence levels are assigned for all three compounds, and the character of the frontier orbitals is identified and analyzed.     

Ligand expansion in ligand-based virtual screening using relevance feedback

Query expansion is the process of reformulating an original query to improve retrieval performance in information retrieval systems. Relevance feedback is one of the most useful query modification techniques in information retrieval systems. In this paper, we introduce query expansion into ligand-based virtual screening (LBVS) using the relevance feedback technique. In this approach, a few high-ranking molecules of unknown activity are filtered from the outputs of a Bayesian inference network based on a single ligand molecule to form a set of ligand molecules. This set of ligand molecules is used to form a new ligand molecule. Simulated virtual screening experiments with the MDL Drug Data Report and maximum unbiased validation data sets show that the use of ligand expansion provides a very simple way of improving the LBVS, especially when the active molecules being sought have a high degree of structural heterogeneity. However, the effectiveness of the ligand expansion is slightly less when structurally-homogeneous sets of actives are being sought.     

On the Reaction of 3-Acetyl Coumarin with Alkyl Phosphites. Structural Confirmations Based on X-Ray Crystallography

3-Acetyl coumarin ( 1 ) reacts with dialkyl phosphites at 100°;C for 8 h to give the phosphonates 2 . Under the same experimental conditions, 1 reacts with trialkyl phosphites to form a mixture of the phosphonates 2 and 3 . The molecular structures of these products were elucidated by x-ray crystallography.     

Miscibility Studies of Dextran/Poly(vinyl pyrrolidone) Blend in Solution

The miscibility of dextran (Dex)/poly(vinyl pyrrolidone) (PVP) in solution has been investigated in different percentages of the blend components by employing viscosity, density, refractive index and ultrasonic velocity methods at 30 and 50°C, respectively. Ultrasonic velocity and adiabatic compressibility against blend compositions were plotted and found to be linear. The interaction parameters μ and α have been obtained by using the viscosity data. The results indicated that the Dex/PVP blends are miscible in the entire composition range and it was further confirmed by ultrasonic velocity, density, refractive index studies. In addition, the results revealed that the change in temperature has no significant effect on the miscibility of Dex/PVP polymer blend.     

The Synthesis of Some New Fused and Substituted Chromenes

Some new chromeno[2,3-b]pyrimidines, chromeno[3,2-c]pyridines, chromeno[2,3-b]pyridines and 3-chromenyl-1,3-thiazines were synthesized via the synthetic studies of the reaction of 2-imino-2H-chromen-3-thiocarboxamide with some aromatic aldehydes, active nitriles, and their ylidene derivatives.     

Dual labeling of biomolecules using MeCAT and DOTA derivatives: application to quantitative proteomics

In this study, single and dual labeling of primary amino and thiol groups of target peptides is presented as a proof of concept. The proposed method allows flexible, independent and sequential labeling of the mentioned residues using lanthanides introduced via DOTA-complexes (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The efficiency of the method was optimized using cysteine-containing standard peptides and then applied to bovine serum albumin (BSA) and human serum albumin (HSA) to demonstrate qualitative and quantitative aspects of this strategy. For amino labeling, cysteinyl peptides were immobilized on Sepharose-6B resin and labeled with DOTA-NHS ester followed by metallation with lanthanides. Thiol labeling was carried out using lanthanide-containing metal-coded affinity tags (MeCAT) after elution of peptides from the resin. Complete dual labeling of the standard peptides was demonstrated by liquid chromatography electrospray ionization mass spectrometry, whereas more than 80% of the detected peptides of BSA and HSA were completely dual-labeled. Parallel detection by LC coupled to inductively coupled plasma mass spectrometry (ICP-MS) delivered reliable quantitative information. Thus, the versatile lanthanide choice in both labeling steps allowed estimating primary amino and thiol stoichiometries for the studied samples using different lanthanides. On the other hand, enhancement of ICP-MS signal was achieved as expected when all positions were labeled with the same lanthanide. Finally, linear calibrations of the signal for most of the labeled peptides by standard additions of digested BSA showed a suitable behaviour for quantitative applications and demonstrated the pre-concentration capability of the employed resin.