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Deuterium Labelling (deuterium + labelling)
Selected AbstractsSynthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronidesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2007Jean-Yves Sancéau Abstract Acolbifene (EM-652·HCl, SCH 57068·HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4,-glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2H-labelled derivatives 4,6 were synthesised for use as preclinical and clinical standards for LC,MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at ,10°C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C2H3MgI followed by dehydration with C2H3CO22H/2H2O. After chemical resolution and salt neutralisation, [2H3]acolbifene 19 was obtained with 99.4% enantiomeric purity and >98% isotopic purity. Copyright © 2007 John Wiley & Sons, Ltd. [source] An improvement to the synthesis of deuterated meso-tetraphenylporphyrinsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2006Motoko S. Asano Abstract An improved method for the synthesis of deuterated tetraphenylporphyrins (TPPs) is reported. In this method, deuterium labelling at the pyrrole,, -position is increased to more than 95 at%. TPP is the most widely used synthetic porphyrin and high deuterium incorporation is essential for spectroscopic studies and kinetic studies involving relaxation processes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Negative ion electrospray ionization mass spectrometry of nucleoside phosphoramidate monoesters: elucidation of novel rearrangement mechanisms by multistage mass spectrometry incorporating in-source deuterium labellingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2008Peng-Xiang Xu Several O-2,,3,-isopropylideneuridine-O-5,-phosphoramidate monoesters were synthesized and analyzed by negative ion electrospray ionization tandem mass spectrometry (ESI-MSn). Two kinds of novel rearrangement reactions were observed due to the difference in the amino acid in the nucleoside phosphoramidate monoesters, and possible mechanisms were proposed. One involves a five-membered cyclic transition state. The other is formation of a stable five-membered ring intermediate by Michael addition. Results were confirmed by tandem mass spectrometry and isotopically labeled hydrogen atoms. Furthermore, the internal hydrogen exchange between active hydrogen and methyl acrylate in the heated capillary of the mass spectrometer was found. The characteristic fragmentation behavior in ESI-MS may be used to monitor this kind of compounds in the biological metabolism. Copyright © 2008 John Wiley & Sons, Ltd. [source] Evidence for an aryl migration during the electron impact induced fragmentation of substituted aryloxymethylquinoxalinesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 3 2002I. Starke The electron impact (EI) mass spectra of 34 differently substituted 2-phenoxymethyl-, 2-naphthyloxymethyl-, 2-pyridinyloxymethyl- and 2-chinolinyloxymethylquinoxalines were recorded. The fragmentation patterns were examined by metastable ion analysis and exact mass measurements, employing finally also selective deuterium labelling. The inclusion of the substituted aryl ring moiety appears to be important for the fragmentation of the aryloxymethylquinoxalines. A molecular ion rearrangement is proposed for the observed loss of OH· and CHO· radicals. The influence of the different substituents on the aryl ring moiety on the rearrangement in the gas phase and on the resulting fragmentation was investigated. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||