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Isotopic Purity (isotopic + purity)
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] Synthesis of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoinJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2003Hongbin Yu Abstract 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was synthesized from the oxidation of 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine with 2 equivalents of Ir(IV) in pH 4.5 potassium phosphate buffer. The synthesis of 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine started with bromination of 1,7,NH2 - 15N3 -2,-deoxyguanosine. The resulting 1,7,NH2 - 15N3 -8-bromo-7,8-dihydro-2,-deoxyguanosine reacted with sodium benzyloxide to afford 1,7,NH2 - 15N3 -8-benzyloxy-7,8-dihydro-2,-deoxyguanosine. Subsequent catalytic transfer hydrogenation of 1,7,NH2 - 15N3 -8-benzyloxy-7,8-dihydro-2,-deoxyguanosine with cyclohexene and 10% Pd/C yielded 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine. Purification of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was first carried out on a C18 column and the product was further purified on a graphite column. ESI-MS was used to confirm the identity and to determine the isotopic purity of all the labeled compounds. The isotopic purity of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was 99.4 atom% based on LC-MS measurements. Copyright © 2003 John Wiley & Sons, Ltd. [source] Improved synthesis of 13C,2H3 - and 2H3 -salmeterol by Cs2CO3 -mediated monoalkylation of a primary amineJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2002Tadeusz F. Molinski Abstract An abbreviated synthesis of isotopically labelled salmeterol has been achieved. The key improvement utilizes a highly selective Cs2CO3 -mediated one-pot alkylation of benzylamine by 6-bromo-1-(4,-phenylbutoxy)hexane to prepare the limiting reagent, 6- N -benzylamino-1-(4,-phenylbutoxy)hexane without overalkylation. The method was applied to synthesis of the title compounds in >97 at% isotopic purity. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis of doubly 13C-labelled antalarmin isotopomers for pharmacokinetic studiesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2002Elisabeth Greiner Abstract Antalarmin (butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H -pyrrolo[2,3- d]pyrimidin-4-yl]-amine) was doubly labelled with carbon-13. The synthesized butyl-[13C2]ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H -pyrrolo[2,3- d]pyrimidin-4-yl]-amine (1) and butyl-ethyl-[2- 13C]-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H -pyrrolo[2,3- d]-[2- 13C] pyrimidin-4-yl]-amine, (2) were prepared for use as substrates for pharmacokinetic studies. These compounds were obtained in fair overall yield in a 5 and 6 step synthesis (20,24.5%, respectively) and high isotopic purity (about 99 at% 13C). Copyright © 2002 John Wiley & Sons, Ltd. [source] High-yield synthesis of milligram amounts of isotopically enriched methylmercury (CH3198HgCl)APPLIED ORGANOMETALLIC CHEMISTRY, Issue 2 2004Chrystelle Bancon-Montigny Isotopically enriched CH3198HgCl (MeHgCl) has been synthesized from commercially available elemental 198Hg (96% isotopic purity). Elemental mercury is first converted to HgCl2 and subsequently reacted with methylcobalamin to produce MeHgCl. The resulting MeHgCl is isolated from the reaction mixture by successive extractions with toluene and dried over Na2SO4. The product structure was verified using gas chromatography,mass spectrometry (GC,MS) and the isotopic composition was determined by GC,inductively coupled plasma MS. The yield obtained is 99%. The proposed method allows preparation of milligram quantities of MeHgCl in one step, minimizing the cost of this synthesis. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||