Bradow J.,Pfizer |
Riley F.,Pfizer |
Philippe L.,Pfizer |
Yan Q.,Pfizer |
And 2 more authors.
Journal of Separation Science | Year: 2015
A fully automated countercurrent chromatography system has been constructed to rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent system series and translate the results to preparative scale separations. The system utilizes "on-demand" preparation of the heptane/ethyl acetate/methanol/water solvent system upper and lower phases. Elution-extrusion countercurrent chromatography was combined with non-dynamic equilibrium injection reducing the screening time for each heptane/ethyl acetate/methanol/water system to 17 min. The result enabled solvent system development to be reduced to under 2 h. The countercurrent chromatography system was interfaced with a mass spectrometer to allow selective detection of target components in crude medicinal chemistry reaction mixtures. Mass-directed preparative countercurrent chromatography purification was demonstrated for the first time using a synthetic tetrazole epoxide derived from a routine medicinal chemistry support workflow. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source
Wood P.L.,Dynamic Extractions Ltd
Journal of Chromatography A | Year: 2010
I-type, J-type and non-synchronous centrifuges are all coil planet centrifuges. Analysing the motion of I-type and J-type centrifuges has advanced the understanding of how to manufacture and use these centrifuges. This paper analyses the motion of non-synchronous centrifuges producing equations of motion that can be applied to all coil planet centrifuges. This has also produced simple equations to determine the critical β-values for any coil planet centrifuge. This paper also demonstrates that I-type centrifuges also have 2 critical β-values when it was thought that β-value did not influence the understanding of the processes within I-type centrifuges. For the I-type instrument both of these critical values are at bobbin radii approaching infinity. In practice this means all I-types function within one β-value range hence the unilateral distribution and type/effectiveness of the mixing is consistent. Finally the paper shows the influence that the tangential velocity has on the Archimedean screw effect and thus the unilateral distribution of the upper and lower phases in the columns of coil planet centrifuges. This explains why the maximum stationary phase retention in an I-type centrifuge is limited to 50%. © 2009 Elsevier B.V. All rights reserved. Source
Dahlberg C.J.,Metagenics |
Harris G.,Dynamic Extractions Ltd |
Urban J.,Metagenics |
Tripp M.L.,Metagenics |
And 2 more authors.
Journal of Separation Science | Year: 2012
Commercially available hops (Humulus lupulus L.) bitter acid extracts contain a mixture of three major congeners (co-, n-, and ad-) in addition to cis/trans diastereomers for each congener. Individual isomerized α-acids were obtained by the consecutive application of two separate countercurrent chromatography methods. First, individual isomerized α-acid congeners as a mixture of cis/trans diastereomers were obtained using a solvent system consisting of hexane and aqueous buffer. The second purification, capable of separating cis/trans diastereomers, was accomplished using a quaternary solvent system; an alternative procedure using β-cyclodextrin followed by countercurrent chromatography was also investigated. The NaBH 4 reduction of the purified isomerized α-acid compounds followed by countercurrent chromatography purification resulted in individual ρ iso α-acids (>95%). Similarly, catalytic hydrogenation of the purified isomerized α-acid compounds followed by countercurrent chromatography purification produced individual tetrahydro isomerized α-acids (>95%). Reported herein is a widely applicable approach that focuses on three critical variables - solvent system composition, pH, and buffer-to-sample ratio - that enable the efficient purification of individual bitter acids (≥95%) from commercially available hops extracts. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Source
DYNAMIC EXTRACTIONS Ltd | Date: 2012-09-28
The invention relates to centrifuge apparatus of a type which is typically, although not necessarily exclusively, for use in counter current chromatography in which substances are caused to partition between two phases in a column typically in the form of a helix or spiral. The apparatus includes leads which connect the inlet and outlet conduits to a column which is moved by the apparatus and in accordance with the invention the leads are constrained within a sheath which includes a lubricant to allow lubrication of the same while the apparatus is in use and thereby increase the longevity of the apparatus. The opposing ends of the leads can also be constrained in terms of movement with, at one end of the leads being fully constrained and the opposing end the leads being constrained in terms of rotational movement.
Roemer T.,Merck Frosst Canada Ltd. |
Xu D.,Merck Frosst Canada Ltd. |
Xu D.,WuXi AppTec |
Singh S.B.,Merck And Co. |
And 5 more authors.
Chemistry and Biology | Year: 2011
Starting with the discovery of penicillin, the pharmaceutical industry has relied extensively on natural products (NPs) as an unparalleled source of bioactive small molecules suitable for antibiotic development. However, the discovery of structurally novel and chemically tractable NPs with suitable pharmacological properties as antibiotic leads has waned in recent decades. Today, the repetitive "rediscovery" of previously known NP classes with limited antibiotic lead potential dominates most industrial efforts. This limited productivity, exacerbated by the significant financial and resource requirements of such activities, has led to a broad de-emphasis of NP research by most pharmaceutical companies, including most recently Merck. Here we review our strategies - both technological and philosophical - in addressing current antifungal discovery bottlenecks in target identification and validation and how such efforts may improve NP-based antimicrobial discoveries when aligned with NP screening and dereplication. © 2011 Elsevier Ltd. All rights reserved. Source