Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)‐Verapamil

We describe herein a highly regio‐ and enantioselective Pd‐catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all‐carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine‐ and pyrazino‐oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to >99:1. Both linear and branched substituents on the olefins were well‐tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O‐methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil.     

Bioanalytical chemistry of cytokines – A review

Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described.     

Determination of aminopolycarboxylic acids at ultra-trace levels by means of online coupling ion exchange chromatography and inductively coupled plasma-mass spectrometry with indirect detection via their Pd-complexes

A new indirect IC-ICP-MS method for the determination of aminopolycarboxylic acids in water samples is described. It is based on the addition of an excess of Pd(II) to water samples. The analytes are forced into very strong and negatively charged palladium complexes, separated by ion exchange chromatography and detected by their palladium content, utilizing an on-line coupled ICP-MS. This method is suitable to determine the concentration of 8 aminopolycarboxylic acids (nitrilotriacetic acid (NTA), (2-carboxyethyl) iminodiacetic acid (β-ADA), methylglycinediacetic acid (MGDA), 2-hydroxyethyl) ethylenediamine triacetic acid (HEDTA), diethylene triamine pentaacetic acid (DTPA), ethylendiamine tetraacetic acid (EDTA), 1,3-diaminopropane tetraacetic acid (1,3-PDTA) and 1,2-diaminopropane tetraacetic acid (1,2-PDTA) at the ng kg⁻¹ level. The method is faster and easier than the established gas chromatography (GC)-method ISO 16588:2002 [1] and up to two orders of magnitude more sensitive than the ion pair chromatography based method of DIN 38413-8. Analytic performance is superior to ISO 16588:2002 and the comparability is good.     

Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse

The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases.