A versatile route to 3-(pyrimidin-4-yl)-imidazo[1,2-a]pyridines and 3-(pyrimidin-4-yl)-pyrazolo[1,5-a]pyridines

A two-step synthesis of 3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridines is presented. The late stage elaboration of the imidazopyridine through a cyclocondensation allows a rapid access to a variety of substitution patterns. The intermediate enol ethers were obtained from inexpensive reagents in a ligand-free Heck coupling. This methodology has been extended to the formation of pyrazolo[1,5-a]pyridines via a formal 1,3-dipolar cycloaddition.     

Surface diffusion in reversed-phase liquid chromatography

More than 40 years ago, Giddings pointed out in “Dynamics of Chromatography” that surface diffusion should become an important research topic in the kinetics of chromatographic phenomena. However, few studies on surface diffusion in adsorbents used in chromatography were published since then. Most scientists use ordinary rate equations to study mass transfer kinetics in chromatography. They take no account of surface diffusion and overlook the significant contributions of this mass transfer process to chromatographic behavior and to column efficiency at high mobile phase flow rate. Only recently did the significance of surface diffusion in separation processes begin to be recognized in connection with the development of new techniques of fast flow, high efficiency chromatography. In this review, we revisit the reports on experimental data on surface diffusion and introduce a surface-restricted molecular diffusion model, derived as a first approximation for the mechanism of surface diffusion, on the basis of the absolute rate theory. We also explain how this model accounts for many intrinsic characteristics of surface diffusion that cannot properly be explained by the conventional models of surface diffusion.     

Two-dimensional liquid chromatography/mass spectrometry/mass spectrometry separation of water-soluble metabolites

Off-line two-dimensional liquid chromatography with tandem mass spectrometry detection (2D-LC/MS-MS) was used to separate a set of metabolomic species. Water-soluble metabolites were extracted from Escherichia coli and Saccharomyces cerevisae cultures and were immediately analyzed using strong cation exchange (SCX)-hydrophilic interaction chromatography (HILIC). Metabolite mixtures are well-suited for multidimensional chromatography as the range of components varies widely with respect to polarity and chemical makeup. Some currently used methods employ two different separations for the detection of positively and negatively ionized metabolites by mass spectrometry. Here we developed a single set of chromatographic conditions for both ionization modes and were able to detect a total of 141 extracted metabolite species, with an overall peak capacity of ca. 2500. We show that a single two-dimensional separation method is sufficient and practical when a pair or more of unidimensional separations are used in metabolomics.     

The influence of water on the memory effect of the amylose tris(3,5-dimethylphenyl carbamate) stationary phase

Acid/base modifiers are sometimes used as additives in normal phase elution on columns packed with CHIRALPAK^® AD^®. These modifiers affect enantioseparations in ways that are not yet fully understood for the lack of systematic studies. Shifts of the selectivity of certain pairs of enantiomers upon exposure of the column to these modifiers is amply documented. Furthermore, once the modifier has been removed from the mobile phase, the modified selectivity remains, which has been named the Memory Effect. After a column has been exposed to an eluent stream containing acidic/basic modifiers, this particular column no longer separates certain enantiomeric pairs with the same selectivity as a modifier naive column. This makes the transfer of developed methods from one to other CHIRALPAK AD columns difficult to predict, if the selectivity needs to be similar between the two columns. We selected four enantiomeric pairs for a systematic study of this Memory Effect. The selectivity of 4-chlorophenylalanine ethyl ester improves after a solution of ethanesulfonic acid (ESA) is percolated through the column. The selectivity of Propranolol and Tröger's base increases after a solution of Diiospropylamine is percolated through the column. The selectivity of Propranolol and Tröger's base enantiomers is inversely affected by percolation of the acid solution. The 4-chlorophenylalanine ethyl ester enantiomers is inversely affected by percolation of the base solution. In contrast, the selectivity of trans-stilbene oxide (TSO) is not affected by either modifier. Analytical studies of the stationary phase suggest that slow protonation/deprotonation of water molecules attached to the carbamate moiety may be responsible for the acid/base Memory Effect. To further the understanding of the effect of water on the Memory Effect, mobile phases – spiked with water (0.01–0.43%) – were used to measure changes in the Memory Effect. Finally, we showed that the influence of water on the Memory Effect can be minimized by percolating through the column a sufficiently concentrated solution of the appropriate base while using dried mobile phases.     

Temporal cleaning of a high-energy fiber-based ultrafast laser using cross-polarized wave generation

We report the use of cross-polarized wave generation to perform both pulse shortening and temporal cleaning of a high-energy ytterbium-doped fiber-based femtosecond laser system. The nonlinear processes allow both a highly efficient nonlinear conversion of 20% and a large compression ratio of 3.5, with inherently improved coherent and incoherent contrasts. This results in the generation of 37 μJ, 115 fs pulses at a repetition rate of 100 kHz with high temporal quality.     

Performance of columns packed with the new shell particles,Kinetex-C18

The performance of the new Kinetex-C₁₈ column was investigated. Packed with a new brand of porous shell particles, this column has an outstanding efficiency. Once corrected for the contribution of the instrument extra column volume, the minimum values of the reduced plate heights for a number of low molecular weight compounds (e.g., anthracene and naphtho[2,3-a]pyrene) were between 1.0 and 1.3, breaking the legendary record set 3 years ago by Halo-C₁₈ packed columns. The liquid-solid mass transfer of proteins (e.g., insulin and lyzozyme) is exceptionally fast on Kinetex-C₁₈ much faster than on the Halo-C₁₈ column. The different contributions of dispersion and mass transfer resistances to the column efficiency were determined and discussed. The possible reasons for this extremely high column efficiency are discussed.     

Application of a process friendly morpholine synthesis to (S,S)-Reboxetine

We report our results on the construction of a morpholine ring system from the corresponding epoxide and amino alcohol. From this study, we were able to convert a previous four-step synthesis into a more efficient two-step process.     

Retention of Naproxen enantiomers on the chiral stationary phase Whelk-O1 under reversed-phase conditions. A reconsideration of the adsorption mechanism in the light of new experimental data

A model of adsorption of the Naproxen enantiomers on the (S,S)-Whelk-O1 chiral stationary phase that we recently proposed was found to be inconsistent with new experimental data. A new model taking into account the variation of the dissociation coefficient of the analyte during elution of the band is discussed.     

Laser mode manipulation by intracavity dynamic holography: Application to mode selection

Intra-cavity dynamic holography is proposed as a self-adaptive, easy to set up technique for efficient laser mode manipulation. A first implementation is presented here as a longitudinal mode selector providing a spectacular spectral narrowing in linear laser cavities operating both in the pulsed and the cw regimes. Received: 12 April 1999 / Published online: 24 June 1999