Abstract Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of candidates their metabolites. Herein we report a photoredox‐initiated hydrogen atom transfer (HAT) protocol which efficiently selectively introduces deuterium or tritium at C(sp 3 )−H bonds, utilizing heavy water (D 2 O T O) isotope source, guanidine base. This has been successfully applied to incorporation...

High-performance liquid chromatography-solid phase extraction-NMR spectroscopy (HPLC-SPE-NMR) has recently become commercially available and been evaluated with regard to its applicability in a pharmaceutical environment. The addition of an automated SPE unit HPLC-NMR system for peak trapping results improved NMR signal-to-noise ratio (S/N) also other practical advantages. efficiency is shown depend on compound polarity highest compounds eluting late reversed-phase HPLC systems. Multiple...

Two unspecific peroxygenases (UPO, EC 1.11.2.1) from the basidiomycetous fungi Marasmius rotula and wettsteinii oxidized steroids with hydroxyacetyl hydroxyl functionalities at C17 - such as cortisone, Reichstein's substance S prednisone via stepwise oxygenation final fission of side chain. The sequential oxidation started hydroxylation terminal carbon (C21) leading to a stable geminal alcohol (e.g. cortisone 21-gem-diol) proceeded second resulting in corresponding α-ketocarboxylic acid...

We have studied the photoredox-catalyzed hydrogen isotope exchange (HIE) reaction with deuterium or tritium gas as sources and in situ formed transition metal nanoparticles atom transfer pre-catalysts. By this means we found synergistic reactivities applying two different HIE mechanisms, namely CH-functionalization leading to synthesis of highly deuterated complex molecules. Finally, adopted these findings successfully chemistry.

The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in renal secretion organic cation transporter 2 (OCT2) and multidrug toxin extrusion proteins (MATE1, MATE2-K). aim of this vitro study was examination interaction with OCT2 MATEs. Memantine inhibition transport were examined HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers single- (MDCK-OCT2, MDCK-MATE1) double-transfected MDCK...

LC-NMR-MS hyphenation has been applied in the screening of an asterosaponin subfraction obtained from starfish Asterias rubens for unknown compounds. The suitability this technique characterizing compounds molecular weight range 1200 to 1400 a.m.u. demonstrated. additional information concerning number exchangeable protons provided by experiment proved be particularly valuable structural elucidation. indicated presence hitherto asterosaponins sample. Based on information, four new...

Enzymatic conversion of a drug can be an efficient alternative for the preparation complex metabolite compared with multi‐step chemical synthesis approach. Limitations exist methods direct oxygen incorporation into organic molecules often suffering from low yields and unspecific oxidation also whole‐cell biotransformation processes, which require specific fermentation know‐how. Stable oxygen‐transferring biocatalysts such as peroxygenases (UPOs) could human metabolites related stable...

Abstract We report two new asterosaponins from the Baltic starfish Asterias rubens along with their 1 H and 13 C NMR data. The compounds were isolated after on‐flow liquid chromatography–NMR–mass spectrometry screening indicated that they had not been identified before. one‐ two‐dimensional experiments used to elucidate structures recorded using a 5 mm cryogenic probe head. advantages of probes for this kind examination in comparison conventional heads are discussed. Copyright © 2003 John...

We have summarized methods for the preparation of phase II metabolites which proven to be successful in our laboratory synthesis selected O-glucuronides and sulfates recent drug development candidates.The syntheses AVE0897 O-acylglucuronide 7, AVE2268 O-glucuronide 12, SAR7226 21 28 MDL107292 33 are described detail.Analytical aspects related specific chromatographic very polar compounds discussed.

Mentha × piperita shoot tips and first leaf pairs were fed with aqueous solutions of different deuterium-labeled pulegone various enantiomeric distributions. The essential oil was extracted by solid-phase microextraction analyzed using enantioselective multidimensional gas chromatography/mass spectrometry. genuine p-menthan-3-ones (−)-menthone (+)-isomenthone as well their labeled analogues simultaneously. Both enantiomers converted into the corresponding piperita, indicating an unspecific...

We describe a simple and easy pathway to synthesize nitrosamine mass spectrometry standards in good moderate yields. N-alkylation of Boc-protected primary or secondary amines using stable isotope labeled alkyl halides yielded the key intermediates that were deprotected, then, was formed with sodium nitrite hydrogensulfate. Special attention safety, disposal waste, surface cleaning carried throughout.

A highly regioselective visible light photoredox‐catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst combination with thiol‐based atom transfer catalyst, while the use D2O as source ensures operational simplicity cost‐effectiveness. High reactivity has been achieved for electron‐rich positions. Moreover, targeted radical formation enables unprecedented...

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Abstract Es wird ein hochgradig regioselektiver, von sichtbarem Licht photoredox‐katalysierter Wasserstoff‐isotopenaustausch (WIA) an benzylischen Positionen einfachen und komplexen Molekülen beschrieben. Der Prozess folgt einem dual katalytischen Ansatz, basierend auf der Kombination eines Acridinium‐Photokatalysators mit Thiol basierten Wasserstoffatomtransfer Katalysator (HAT). Die Verwendung D 2 O als Isotopenquelle gewährleistet hierbei eine einfache Handhabung Kosteneffizienz. konnte...

Pulegone, menthone, and isomenthone isotopomers are synthesized as regioselectively deuterated d(5)- d(8)-stereoisomers. Deuterium-labeled menthone enantiomers analyzed using enantioselective multidimensional gas chromatography/mass spectrometry. The stereoisomers of separated from the unlabeled on a glass capillary column, coated with 50% octakis(2, 3-di-O-butyryl-6-O-tert- butyldimethylsilyl)-gamma-cyclodextrin in OV 1701vi chiral stationary phase. These deuterium-labeled monoterpene...

Tritium‐labeled compounds are generally less stable than their non‐labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re‐purifications. As the amount tritium‐labeled material is typically purified in μg range, repeated injections on analytical‐scale ultra high‐performance liquid chromatography systems can provide high‐resolution re‐purification results. Yet, degradants be undesirably included compound isolation because...

Abstract We have studied the photoredox‐catalyzed hydrogen isotope exchange (HIE) reaction with deuterium or tritium gas as sources and in situ formed transition metal nanoparticles atom transfer pre‐catalysts. By this means we found synergistic reactivities applying two different HIE mechanisms, namely CH‐functionalization leading to synthesis of highly deuterated complex molecules. Finally, adopted these findings successfully chemistry.