bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolution of tritium‐labelled amino acid racemates by ligand‐exchange chromatography. Part 1. Method for obtaining L‐ and D‐[3H]valine using a polystyrene resin with L‐hydroxyproline groupings
Authors: N. F. Myasoedov , O. B. Kuznetsova , O. V. Petrenik , V. A. Davankov , Yu. A. Zolotarev
Published: October 2006

Ligand‐exchange chromatography is shown to be applicable for obtaining the optical isomers of [3H]valine. Data are presented showing the effect of the asymmetric sorbent's structure on its kinetic properties and the optimum conditions selected for the chromatographic resolution of D, L‐[3H] valine. The method makes it possible to obtain both isomers of [3H]valine with an optical purity close to 100% in about 2 hours with a simultaneous radiochemical purification. The method does not require any preliminary chemical modification of the amino acid and does not impose any limitations to specific activity values.
Tritium labelling and tritium N.M.R. ‐ part I alpha‐labelled stearic, palmitic, myristic and lauric acids
Authors: Crossley P. C. , Martin R. W. , Mawson J. B. , Odell A. L.
Published: October 2006

Stearic, palmitic, myristic and lauric acids have been labelled with tritium in the alpha carbon position, and the position of the label confirmed using tritium N.M.R. spectrometry. The α‐3H acids were prepared using tritiated water with sulphuric acid or sodium hydroxide as catalysts. Specifically labelled compounds of high specific activity and radiochemical purity were obtained.
Synthesis of deuterium‐labelled N,N‐dimethyl‐morpholinium‐ and N‐methyl‐N‐ethyl‐morpholinium‐ 7,7,8,8‐tetracyanoquinodimethane complexes
Authors: Kwant B. H.
Published: October 2006

Attempted exchange experiments of morpholine, N‐methylmorpholine and N‐ethylmorpholine with a deuterium donor led to no deuterium incorporation in the morpholine rings. Morpholine‐d8 is not found in the reaction of bromoethanol‐d5 and ammonia, but it can be prepared from ethyleneoxide‐d4 and ammonia. These reaction conditions are given for the H‐analog. N‐methylmorpholine‐d11 is prepared from ethyleneoxide‐d4 and methylamine‐d5 N‐ethylmorpho‐Line‐d13 is prepared in an analogous manner. N‐methyl‐d3‐morpholine is prepared from morpholine and diazomethane‐d2 or from morpholine and methyliodide‐d3 or from 2,2′‐bis‐(iodoethyr)ether and methyllamine‐d5 N‐methyl‐N‐ethyl‐d5‐morpholinium(M.E.M.‐d5)‐iodide is preparea from N‐methylmorpholine and ethyliodide‐d5 M.E.M.‐d16‐iodide and M.E.M.‐iodide are obtained by a similar route. N,N‐di‐(methyl‐d3)‐morpholiniumiodide is prepared from N‐methyl‐d3Morholine and methyliodide‐d3 and also from morpholine and methyliodide‐d3 M.E.M.‐(T.C.N.Q.‐d4)2; M.E.M.‐d5‐(T.C.N.Q.‐d4)2; M.E.M. d16‐(T.C.N.Q.‐d3)2; M.E.M.‐d16‐(T.C.N.Q.)2; and N,N‐di‐(methyl‐d3)‐ morpholinium‐(T.C.N.Q.)2 are prepared from the deuterated or undeuterated morpholiniumiodides and T.C.N.Q. All synthetic methods are described in detail.
Synthese De L'Acide Dimercapto‐2,3 Succinique‐14C‐2,3
Authors: Compagnon P.‐L. , Kimny Tan , Rapin J. R.
Published: October 2006

The synthesis of 14C‐2,3 dimercapto sucinic acid (DMSA) is described. The starting material 14C‐2,3 succinic acid was brominated and then deshydrohalogenated to give acetylenedicarboxylic acid. This 14C‐acetylenic compound was transformed into 14C‐dithioacetylsuccinic acid. This latter compound was hydrolysed with sodium hydroxyde to give 14C‐DMSA. The overall yield was 57% at a specific activity of 1.6 mCi/mM.
A simple and efficient synthesis of [3H]cholesteryl 14‐methylhexadecanoate
Authors: Helmich O. , Hradec J.
Published: October 2006

The reaction of labelled cholesterol with a large excess of freshly prepared 14‐methylhexadecanoyl chloride in a simple glass apparatus was used for the synthesis of [3H]cholesteryl 14‐methylhexadecanoate in microgram amounts. After purification of the crude product by thin‐layer chromatography, the purity of the final preparation was better than 98% as checked by gas‐liquid and high‐pressure liquid chromatography. On average 90% of the input radioactivity was present in the ester. The same technique was also used for the preparation of [14C]cholesteryl 14‐methylhexadecanoate and [3H] or [14C]cholesteryl laurate, myristate, palmitate, margarate and stearate with similar yields. All these preparations were found suitable for biochemical studies.
Convenient methods for the preparation of [5‐14C]‐4‐ipomeanol and [3H(G)]‐4‐ipomeanol of high specific radioactivity
Authors: Boyd Michael R. , Dutcher John S.
Published: October 2006

Procedures are described for the preparation of radiolabeled 4‐ipomeanol [1‐(3‐furyl)‐4‐hydroxypentanone], a highly selective pulmonary alkylating agent, of sufficiently high specific radioactivity for biochemical and autoradiographic studies. The 14C‐labeled material is prepared from the reaction of ethyl 3‐fur‐oylacetate with [3‐14C]‐propylene oxide; the tritiated product is obtained by catalytic tritiation using T2O or tritium gas as the source of the radiolabel.
Synthesis of microamounts of ketones from carboxylic acids: 1‐phenoxy‐2‐butanones‐2‐14‐14C
Authors: Look Melvin
Published: October 2006

A technique using acetic acid as a co‐reactant for synthesizing microamounts of radiolabelled ketones from carboxylic acids with ethyl lithium is described. The acetic acid forms methyl ethyl ketone, a compound easily separated from the radiolabelled products.
Synthesis of tritium labelled 4‐fluoro‐1‐[1–(2‐thienyl)]cyclohexylpiperidine ([3H]‐FTCP); a tool for autoradiographic study of the phencyclidine binding site
Authors: Thurkauf Andrew , De Costa Brian R. , Kiesewetter Dale O. , Jacobson Arthur E. , Rice Kenner C.
Published: October 2006

4‐Fluoro‐1–[1–(2‐thienyl)‐3‐cyclohexenyl)] piperidine was efficiently synthesized in four steps starting from cyclohexane‐1, 4‐dione monoethylene ketal. Catalytic tritiation of this key intermediate in the final step afforded the title compound.
Optimized synthesis of radioiodinated rhodamine‐123
Authors: Vora Manhar M. , Lambrecht Richard M.
Published: October 2006

Rhodamine‐123 (Rh123) was iodinated with 123I in presence of Iodogen. Yield of the labelled Rh123 varied greatly depending upon various reaction parameters. Optimum reaction conditions with respect to molarity and pH of the buffer, reaction time, amounts of iodogen, carrier iodide and Rh123, were determined through carefully controlled reactions. Radiochemical yields of 50–60% were obtained within less than 2 hrs. using 0.05M NH4H2PO4 buffer at pH5, 200 μg iodogen, 250 μg Rh123 and no‐carrier‐added iodide. Separation of the labelled Rh123 in greater than 98% radiochemical purity was achieved by flash chromatography on silica gel. The overall isolated yield of radioiodinated Rh123 ranged from 25–35% with respect to the added radioiodide. TLC and HPLC methods were developed for analysis of the labelled products.
Synthesis of a cleavable heterobifunctional photolabelling reagent: Ring‐labelled 3‐[(4‐azidophenyl)dithio]propionic acid‐14C
Authors: Ramaswami Varadarajan , Tirrell David A.
Published: October 2006

An efficient synthesis of ring‐labelled 3‐[(4‐azidophenyl)dithio]propionic acid‐14C is described. Chlorosulfonation of uniformly ring‐labelled acetanilide‐14C followed by reductive dimerization of the sulfonyl chloride with HI afforded 4‐acetamidophenyl disulfide. Hydrolysis and diazotization then gave 4‐azidophenyl disulfide, which was converted to the title compound via the sulfur transfer reagent N‐(4‐azidophenylthio)phthalimide. The overall yield of 3‐[(4‐azidophenyl)dithio]propionic acid‐14C was 22%. 3‐[(4‐Azidophenyl)dithio]propionic acid‐14C is a cleavable heterobifunctional photolabelling reagent of potential utility in studies of biomembrane structure and intermacromolecular interaction.
Synthesis of 14C labelled acrylic derivatives: Diethyl [3‐14C] methylidenemalonate and isobutyl [3‐14C] cyanoacrylate
Authors: De Keyser Jean‐Luc , De Cock Christian J. C. , Poupaert Jacques H. , Dumont Pierre
Published: October 2006

Isobutyl [3‐14C] cyanoacrylate and diethyl [3‐14C] methylidenemalonate were synthesized by the intermediate of their protective Diels‐Alder adduct with anthracene. These adducts (2a‐b) were obtained in a one‐pot procedure by Knoevenagel condensation of [14C] paraformaldehyde with isobutyl cyanoacetate and diethyl malonate respectively in the presence of a basic catalyst and anthracene. The adducts are stable crystalline compounds easily purified by recrystallization. The olefinic target coumpounds (1a‐b) were obtained in high chemical and radiochemical purity (>99%) by thermolysis at 220 °C in mineral oil in the presence of maleic anhydride.
Synthesis of [17O]‐ and [18O]‐labelled hypophosphate
Authors: Potter Barry V. L.
Published: October 2006

The preparation of 17O‐ and 18O‐labelled hypophosphate by oxidation of diphosphite (P2‐P4 acid) with iodine‐water is described. The 162 MHz NMR 31p(18O) isotope shift of 18O‐labelled hypophosphate is 2.42 Hz (0.0149 ppm), the relatively large value compared to 18O‐pyrophosphate, 1.73 Hz (0.0107 ppm), being suggestive of an as yet unobserved 31P(18O) β‐isotope shift of 1.38 Hz (0.009 ppm)
Use of solvent vapour pressure to evacuate the installation in carbonations of grignard reagents
Authors: Schiketanz Ana , Pogany Iuliu , Gheorghiu Mircea D. , Necula Atena , Balaban Alexandru T.
Published: October 2006

An installation is described for the carbonation of organomagnesium reagents with 13CO2 or 14CO2. The obtained vacuum results by sweeping all permanent gases with solvent vapour (ethyl ether or tetrahydrofuran) at room temperature under moderate vacuum. Specific steps in the carbonation procedure are indicated, leading to good yields of carboxyl‐labelled acids.
Synthesis of 3‐quinuclidinol‐18O, benzilic‐d5 acid, and 3‐quinuclidinyl‐18O benzilate‐d5
Authors: Sniegoski Lorna T. , Byrd Gary D. , White V Edward
Published: October 2006

Isotopically labeled analogs of 3‐quinuclidinol (Q), benzilic acid (BA), and 3‐quinuclidinyl benzilate (BZ), for use as internal standards for isotope dilution measurements and the labeled intermediates 3‐quinuclidinone and methyl benzilate used in their production, were synthesized. The isotopic purities of the 1‐azabicyclo[2.2.2]octan‐3‐18O‐ol, α‐hydroxy‐a‐phenyl‐d5‐benzeneacetic acid, and 3‐quinuclidinyl‐18O benzilate‐d5 were determined and the electron impact ionization mass spectrum was obtained for each.
Syntheses of [2‐13C] and [1,2‐13C] labelled α‐ketoglutaric acid
Authors: Baldwin Jack E. , Adlington Robert M. , Russell Mark A. , Schofield Christopher J. , Wood Mark E.
Published: October 2006

The syntheses of α‐keto[2‐13C]glutaric acid and α‐keto[1,2‐13C]glutaric acid were each achieved from commercial 13CH3I in 5 steps. 13CH3NO2, prepared in situ from 13CH3I and AgNO2, was treated with magnesium methyl carbonate, followed by acidified methanol to give O2N13CH2CO2CH3. Michael addition to methyl acrylate, followed by in situ nitronate formation and ozonolysis gave the dimethyl ester of α‐keto [2‐13C]glutaric acid, which was deprotected with hydrochloric acid. O2N13CH213CO2CH3 was prepared from 13CH3NO2 by reaction with aqueous KOH, followed by treatment with acidified methanol, and was converted to 1,2‐13C‐α‐ketoglutaric acid in a similar fashion to that used for mono‐labelled material.
Synthesis of 9‐[(2‐chloro‐6‐fluorophenyl) [14C]methyl]‐9H‐purine‐6‐amine (arprinocid) and 9‐[(2,6‐dichlorophenyl) [14C]methyl]‐9H‐purine‐6‐amine
Authors: Ellsworth Robert L. , Meriwether Henry T. , Mertel Holly E.
Published: October 2006

The synthesis of 9‐[(2‐chloro‐6‐fluorophenyl)methyl]‐9H‐purin‐6‐amine (arprinocid, a coccidiostat candidate) and 9‐[(2,6‐dichlorophenyl)methyl]‐9H‐purin‐6‐amine labeled with carbon‐14 in the benzylic methylene carbon of each of these is described. Introduction of the carbon‐14 label leading to the formation of the key radioactive intermediates, 2‐chloro‐6‐fluoro[carboxyl‐14C]benzoic acid and 2,6‐dichloro‐[carboxyl‐14C]benzoic acid, was accomplished by utilizing [14C]carbon dioxide for carbonation of a suitable dihalo‐phenyl Grignard or organolithium reagent.
Synthesis of 2‐[4‐(diphenylmethyl)‐1‐piperazinyl]ethyl methyl (±)‐1,4‐dihydro‐2,6‐dimethyl‐4‐(m‐nitrophenyl)‐3,5‐[6‐14C]pyridinedicarboxylate dihydrochloride ([14C]CV‐4093 (2HCl))
Authors: Tada Norio , Kajino Masahiro , Watanabe Masazumi , Hayashi Nobuyoshi
Published: October 2006

The carbon‐14 labelled compound (5) of 2‐[4‐(diphenylmethyl)‐1‐piperazinyl]ethyl methyl (±)‐1,4‐dihydro‐2,6‐dimethyl‐4‐(m‐nitrophenyl)‐3,5‐pyridinedicarboxylate dihydrochloride (CV‐4093 (2HCl)) was synthesized for the study of its metabolism and distribution in test animals. Starting from the commercially available ethyl[3‐14C]acetoacetate (1), 5 was prepared by a modified Hantzsch synthesis, in an overall radiochemical yield of 23.7%.
Synthesis and NMR spectra of 17oxygen enriched phenols
Authors: Bank Shelton , Longley Kathryn L.
Published: October 2006

An efficient and convenient method of preparing 17O enriched phenols is described. Aryl boronic acids are oxidized with 17O enriched potassium hydroperoxide. The 17O labeled potassium hydroperoxide is prepared from the autoxidation reaction of benzhydrol with 17O enriched oxygen gas in the presence of potassium t‐butoxide. [0–17]Phenol, p‐bromo[0–17]phenol and p‐methoxy[0–17]phenol were prepared in good to modest overall chemical yields (40–60%) and high isotopic retention (82–90% from 16.8 atom % 17O2 starting material). 17O NMR spectra of the three enriched phenols demonstrate the benefits of using enriched samples in reducing the total experiment time and greatly improving the signal‐to‐noise ratio compared to unenriched samples.
Enzymatic synthesis of carbon‐11 N‐acetyl‐D‐glucosamine
Authors: Mannens Geert , Slegers Guido , Goethals Patrick , Claeys Albert
Published: October 2006

An enzymatic synthesis of [11C]N‐acetyl‐D‐glucosamine is described. 11CO2 is reacted with methylmagnesium bromide to form [1‐11C]acetate. The latter is converted to [11C]acetylcoenzyme A by passage over an enzyme reactor containing immobilized acetylcoenzyme A synthetase (Acetate: CoA ligase (AMP forming); EC 6.2.1.1).

[11C]Acetylcoenzyme A is purified on‐line and concentrated on an anionexchange column. Elution is achieved with 1.5 M glucosamine HCl pH 8.0 and the [11C]acetylcoenzyme A fraction is collected in an ultrafiltration cell containing the enzyme glucosamine N‐acetyltransferase (acetylcoenzyme A: 2‐amino‐2‐deoxy‐D‐glucose N‐acetyltransferase EC 2.3.1.3).
Syntheses of homologous, tritium‐labelled photoaffinity analogs of the natural juvenile hormones JH I, JH II, and JH III
Authors: Ujváry István , Eng Wai‐Si , Prestwich Glenn D.
Published: October 2006

Enantiomerically enriched (≥92% e.e.) tritium‐labelled diazoacetate photoaffinity analogs EBDA and EHDA (each 58 Ci/mmol) and EFDA (14 Ci/mmol) were prepared from the corresponding tritiated juvenile hormone (JH) homologs JH I, JH II, and JH III in two steps. Selective reduction of the ester group and subsequent acylation gave the target compounds.
Oxygen present during azeotropic drying drastically reduces the radiochemical yield of 2‐FDG
Authors: Votaw John R. , Satter Martin R. , Jerome Nickles R.
Published: October 2006

The effect of varying reaction conditions on the yield of 2‐FDG via the Jülich synthesis (1) has been investigated. The yield is found to be relatively immune to changes in many reaction parameters. On the other hand, we have found that the type of sweep gas used to remove the vapor phase during the azeotropic drying step is critical. The incorporation of 18F into the 2‐FDG triflate precursor is reduced fourfold when the sweep gas contains oxygen. However, using either of the inert gases nitrogen or helium as the sweep gas insures a consistent 65% 18F incorporation. This phenomena was investigated with proton and 19F NMR spectroscopy at the University of Wisconsin. Oxygen in the sweep gas does not alter the proton environment of the phase‐transfer catalyst (Kryptofix K222) but it does change the environment of the 18F atom, that is loosely bound to the crown ether, inducing less favorable conditions for the SN2 reaction.
Synthesis of ω‐labelled fatty acids
Authors: Tamvakopoulos C. S. , Anderson V. E.
Published: October 2006

A synthetic procedure for producing isotopically ω‐labelled fatty acids is described. The isotopic label is introduced by reducing an ω‐tosylate with either labelled sodium borohydride or labelled lithium dimethyl cuprate.
Synthesis of [14C]‐pargyline {N‐methyl‐N‐([1‐14C]‐propargyl)benzylamine} with the radioactive label on the propargyl group
Authors: Goon David J. W. , Elberling James A. , Demaster E. G. , Nagasawa Herbert T.
Published: October 2006

A one‐pot reaction scheme leading to 14C‐labeled pargyline (N‐methyl‐N‐ propargylbenzylamine) where in the radioactive label from [14C]‐formaldehyde is synthetically incorporated into the methylene group of the propargyl side chain is described. Thus, [14C]‐formaldehyde (aqueous solution) is condensed in solvent dioxane with N‐methyl‐benzylamine and mono‐trimethylsilylacetylene in the presence of cupric acetate dihydrate at elevated temperatures (85–86°) for 24 hrs. The Mannich condensation product is then desilylated and the radiolabeled pargyline is purified by partitioning in ether from acid and base followed by flash chromatography, and isolated as the hydrochloride. The radioactive yield is 58%. This method should be generally applicable for the incorporation of radioactive label into the propargyl methylene group of other drugs containing a propargyl side chain.
Synthesis of tritiated leukotriene antagonist SK&F 104353
Authors: Shu Arthur Y. L. , Richard Heys J. , Mastrocola Antonietta R.
Published: October 2006

Tritium labeled isotopomers of (2S,3R)‐3‐[(2‐carboxyethyl)thio]‐3‐[2‐(8‐phenyloctyl)phenyl]‐2‐hydroxypropionic acid (SK&F 104353) with high specific activity were prepared by catalytic tritiation of the corresponding halogenated and unsaturated precursors. These precursors were synthesized from their respective benzaldehydes using a core sequence (Darzens Condensation, epoxide opening and base‐induced retroaldol reaction) to generate the required alpha‐hydroxy propionic acid moiety. Upon tritiation, the halogenated substrate provided the dimethyl ester derivative having a specific activity of 55 Ci/mmol, while the unsaturated precursor led directly to [3H]SK&F 104353 with a specific activity of 138 Ci/mmole.
Synthesis of 7‐amino‐9a‐methoxy‐10‐[14C]carbamoyl mitosane (10‐[14C]carbamoyl mitomycin C)
Authors: Haynes U. J. , Swigor J. E. , Kaneko T.
Published: October 2006

The synthesis of the title compound (5) is described. Treatment of mitomycin C with sodium methoxide gave decarbamoyl mitomycin C (2). Reaction with acetic anhydride in methanol yielded N1a‐acetyl‐mitomycin C (3). Treatment with [14C]phosgene in the presence of N,N‐dimethylaniline yielded [14C]chloroformate (4). Conversion of the chloroformate to the carbamate and removal of the protecting group with excess ammonia produced the title compound (5).
Synthesis of [35s]‐labelled MK‐0571, a potent antagonist of LTD4
Authors: Williams Haydn W. R. , Young Robert N. , Zamboni Robert , Shaw D. R. D.
Published: October 2006

The synthesis of 5‐[3‐{2‐(7‐chloroquinolin‐2‐yl)ethenyl}‐phenyl]‐8‐dimethylcarbamyl‐4,6‐[6‐35S]dithiaoctanoic acid at a specific activity of 1350 Ci/mmol is reported. This compound is a reagent suited for selective affinity binding studies at the LTD4 receptor.
Synthesis of two 14C‐labeled forms of prinomide, a potential anti‐inflammatory compound and its hydroxy metabolite, labeled with 14C
Authors: Chaudhuri Naba K. , Markus Bohdan
Published: October 2006

The synthesis of two 14C‐labeled forms of prinomide, compounds 7 and 10, and the synthesis of a 14C‐labeled form of its hydroxy metabolite are described. Compound 7 was synthesized by the reaction of phenyl isocyanate and 1‐methyl‐β‐oxo‐pyrrole‐2‐propanenitrile‐carbonyl‐14C (6), which was synthesized in three steps from 1‐methylpyrrole and 14CO2. Cpmpound 10 was synthesized by the reaction of 8, the unlabeled form of the above ketonitrile, and ring‐labeled phenyl isocyanate (9), which was synthesized in three steps from benzene‐14C. The 14C‐labeled form of the hydroxy metabolite 14 was synthesized by reaction of 4‐methoxyphenyl isocyanate and the 14CN‐labeled ketonitrile 12, followed by demethylation with boron tribromide. Labeled ketonitrile 12 was synthesized from 1‐methylpyrrole, by reaction with chloroacetonitrile, followed by replacement of the chlorine atom by a 14CN group.
An improved procedure for the synthesis of DL‐[2‐13C]‐glutamic acid
Authors: Potrzebowski Marek J. , Stolowich Neal J. , Ian Scott A.
Published: October 2006

A convenient two‐step chemical synthesis of DL‐[2‐13C]‐glutamic acid from methyl acrylate and diethyl acetamidomalonate is described. Synthesis of the Michael adduct (III) was effected in quantitative yield by employing strong amino bases as catalysts. The reactivities of three such catalysts, tetramethyl guanidine (TMG), 1,8‐diazobicyclo [5,4,0]‐undec‐7‐ene (1,5‐5) (DBU) and 1,5‐diazobicyclo [4,3,0] non‐5‐ene (DBN) were compared by 13C NMR and all are shown to catalyse the reaction quantitatively, however at markedly different rates.
Rapid synthesis of radiolabeled phenylethanolamine
Authors: Hussain Munir A. , Chaney James E. , Jay Michael , Digenis George A.
Published: October 2006

A method for the rapid synthesis of [14C]‐phenylethanolamine (PEOH) amenable to the preparation of [11C]‐PEOH was developed under anhydrous conditions. Reaction of benzaldehyde with [14C]‐NaCN in the presence of crown ethers in THF yielded [14C]‐cyanohydrin which was reduced to [14C]‐PEOH with borane in the same solvent. The overall chemical and radiochemical yields were 33%.
A tritiated photolabel specific for the active site of monoamine oxidase
Authors: Backwell F. R. C. , Williams C. H.
Published: October 2006

We report the synthesis of a tritiated inhibitor of monoamine oxidase, containing a photolabile azido group. The compound, N‐(4‐azido‐2‐nitrophenyl)‐N′‐3‐[3H]‐methyl‐N′‐(3‐prop‐1‐ynyl)‐1,3‐diamino propane, is a novel, specific photolabel designed to interact covalently with the flavin of the enzyme in absence of light and to form a second covalent linkage with the polypeptide on photoirradiation. The compound is shown to label a sample of monoamine oxidase isolated from bovine liver, and may be useful in helping to map the active site of the enzyme.
A modified procedure for the preparation of macroaggregated albumin (MAA) kits to be labelled with 99mTc for lung scanning
Authors: Al‐Uanabi M. A. , Moussa S. O.
Published: October 2006

A method is reported for the preparation of lyophilized MAA kits for 99mTc labelling in a single step process. High radiochemical yield was obtained. Lung and liver uptake in mice were determined to be 97% and 0.2% respectively.
Synthesis of 4‐protio‐3‐carbamoyl‐2,2,5,5‐tetraperdeuteromethyl‐3‐pyrrolin‐1‐yloxy (mHCTPO): A selectively isotopically labeled compound for use in T2 spin label oxymetry
Authors: Lin Yawares J. , Teicher Beverly A. , Halpern Howard J.
Published: October 2006

The title compound (mHCTPO) has been prepared to enhance sensitivity to molecular oxygen concentration in its Electron Spin Resonance (ESR) spectrum. The synthesis involved a novel variant of the traditional nitroxide synthesis leading to a much improved yield of mHCTPO over the several steps of the synthesis. An enhancement of T2 spin label oxymetry with independent measurment of spin label concentration (from a spectral feature) has been observed. This molecule represents a new class of potentially valuable compounds for in vivo application and for imaging in ESR oxymetry.
Synthese du methyl [(chloro‐2 ethyl)‐3 nitroso‐3 ureido]‐3 didesoxy‐2, 3 α‐D‐arabino‐hexopyrannoside marque AU carbone‐14 OU −AU carbone‐13 (CY 233 ‐ SR 90098)
Authors: Sion R. , Schumer A. , Van Durme E. , Gouyette A. , Geslin M. , Fournier J. P. , Berger Y. , Roger P.
Published: October 2006

CY 233 (Ecomustine or SR 90098) is a new antitumour nitrosourea: it is characterized by a 2‐chloroethylnitrosourea substituent on a dideoxycarbohydrate. It has been labelled with 14C on a) the carbonyl group of the urea in four stages starting with 14COCl2, b) the second carbon of the chloroethyl group in four stages starting with [14C] ethanolamine, and c) on the methyl group on the anomeric centre of the carbohydrate in three stages starting with 14CH3OH. The final position was also labelled with 13C starting with 13CH3OH. These differently labelled compounds are suitable for mechanistic studies of antitumour activity.
Synthese D'un nouveau peptide immunoactif marque AU carbone 14: L'acide N2‐[N‐[N‐lauroyl‐L‐alanyl (14C‐1)]‐γ‐D glutamyl]‐L,L‐diamino‐2,6‐pimelamique (RP 56 142 14C)
Authors: Pham P. , Noel J. P. , Beaucourt J. P. , Vanhove A. , Pacot D. , Bouchaudon J. , Sante Rhone‐Poulenc
Published: October 2006

La synthégse du peptide immunoactif RP 56 14C a été réalisée par synthése peptidique en solution à partir de L‐alanine ∥14C−1) d'acitvité spgcifique 52.5 mCi/mmol (1.94 GBq/mmol).
Chlorodideuteriomethyl‐lithium: A useful reagent for gem‐dideuterated organic compounds
Authors: Barluenga José , Fernández‐Simón José L. , Concellón José M. , Yus Miguel
Published: October 2006

The reaction of ketones (6), at −78°C, with in situ generated chlorodideuteriomethyl‐lithium followed by lithiation leads to the dianionic intermediate (7) which yields dideuterioalkenes (8) by warming or reacts with electrophiles such as dimethyl disulphide affording the compound (9); the same reaction sequence starting from benzoyl chloride leads to the cyclopropanol (12); when the intermediate in this last process (11) was warmed in absence or presence of lithium iodide the expected products (13) or (14) are respectively isolated.
Synthesis of nonadeutero‐clenbuterol
Authors: Ehrhardt J. D.
Published: October 2006

The synthesis of nonadeutero‐clenbuterol, a useful tool for the quantitation of clenbuterol by gas chromatography‐mass spectrometry, is described.
Synthesis of [18F]GBR 12909, a dopamine reuptake inhibitor
Authors: Haka Michael S. , Kilbourn Michael R.
Published: October 2006

Preparation of no‐carrier‐added fluorine‐18 labeled GBR 12909 (1‐[2‐(bis(4‐fluorophenyl)methoxy)ethyl]‐4‐(3‐phenylpropyl)piperazine), a specific and high affinity inhibitor of dopamine reuptake, is described. 4‐Fluoro‐4′‐[18F]fluorobenzophenone was prepared by [18F]fluoride ion substitution of the corresponding trimethylammonium trifluoromethanesulfonate salt. The [18F]benzophenone was reduced to the benzhydrol, chlorinated, then used to alkylate 1‐(2‐hydroxyethyl)‐4‐(3‐phenyl‐propyl)piperazine to yield [18F]GBR 12909 in high specific activity (≥2000 Ci/mmol) and overall yields of 10–16% (corrected, 140 min synthesis).
Synthesis of 14C‐labelled (S)‐(+)‐2‐[4‐(p‐fluorobenzoyl)‐1‐piperidyl]‐1‐naphthylethanol hydrochloride
Authors: Karibe Norio , Rosser R. M. , Ueda Masataka , Sugimoto Hachiro
Published: October 2006

14C‐labelled (S)‐(+)‐2‐[4‐(p‐fluorobenzoyl)‐1‐piperidyl]‐1‐naphthylethanol hydrochloride (5), an anti‐ischemic drug, was synthesized for studying the pharmacokinetic profiles of the compound in four steps using 2‐[carbonyl‐14C]acetonaphthone (1) as a labelled starting material.
Synthesis of carbon‐14 and sulfur‐35 labeled clorsulon
Authors: Gatto Gregory J. , Mertel Holly E.
Published: October 2006

Preparation of the title compound, tracer substances required for the development of the fasciollide clorsulon, is described. The ring‐u‐14C variety was obtained in 42.2% yield overall from purchased [ring‐u‐14C]acetophenone.
Synthesis of 2‐(5‐(4‐[123I/131I]iodophenyl)pentyl)‐oxirane‐2‐carboxylic acid
Authors: Abbas H. G.  , Hankes L. V.  , Feinendegen L. E.
Published: October 2006

A method is described for the synthesis, purification and radiolabelling of 2‐{5‐(4‐iodophenyl)pentyl}oxirane‐2‐carboxylic acid (I‐POCA). This new compound was synthesized from 5‐phenyl‐pentylbromide (1), prepared via 5‐phenyl‐1‐pentanol and subsequently converted to diethyl 5‐phenylpentylmalonate (2). The latter on alkaline hydrolysis yielded ethyl 5‐phenyl‐pentylmalonate (3). Para‐substitution of iodine on the phenyl moiety of the monoester (3) was accomplished by reacting compound (3) with thallium trifluoroacetate (TTFA) and subsequently with KI. Oxidation of ethyl 7‐(4‐iodophenyl)‐2‐methyleneheptanoate (5), which was synthesized from the monoester, ethyl 5‐(4‐iodophenyl)pentylmalonate (4) yielded ethyl 2‐{5‐(4‐iodophenyl)pentyl}oxirane‐2‐carboxylate (6). The radiolabelling procedure was based on a Cu(I)Cl‐assisted, isotopic exchange reaction, which produced a no‐carrier‐added and regiospecific radioiodination with a 32‐52% radiochemical yield.
Total synthesis of fully tritiated leu‐enkephalin by enzymatic coupling
Authors: Hellio F. , Lecocq G. , Morgat J. L. , Gueguen P.
Published: October 2006

This paper describes the total enzymatic synthesis of Leu‐enkephalin (Tyr‐Gly‐Gly‐Phe‐Leu) in which all residues were labelled with tritium. Carboxypeptidase Y from Saccharomyces cerevisiae was the coupling enzyme. [3H]‐Tyr‐NH2, [3H]‐Gly‐Oet, [3H]‐Phe‐NH2 and [3H]‐Leu‐NH2 were prepared with specific radioactivities ranging between 20 and 60 Ci/mmol (740 to 2220 GBq/mmol). Using a microscale procedure, we obtained a fully tritiated hormone having a specific radioactivity equal to 139 Ci/mmol (5143 GBq/mmol), in agreement with the summation of the specific radioactivities of constituting residue. The radioactive hormone had antigenic properties identical to those of native Leu‐enkephalin. It also bound to rat brain opiate receptors like the parental hormone.
[11C]Methylenetriphenylphosphorane, a new 11C‐precursor, used in a one‐pot wittig synthesis of [β‐11C]styrene
Authors: Kihlberg Tor , Gullberg Per , Långström Bengt
Published: October 2006

Preparation of [11C]methyltriphenylphosphonium iodide and the in situ generation of [11C]methylenetriphenylphosphorane directly from [11C]methyl iodide, is described. Using this one‐pot preparation, [β‐11C]styrene was synthesized conveniently, fast and with a minimum of manual handling. The synthesis was performed by using [11C]methyl iodide, triphenylphosphine, epichlorohydrin and benzaldehyde in tetrahydrofurane/o‐dibromobenzene, with a synthesis time of 40 min (counted from the end of [11C]methyl iodide transfer), a radiochemical yield of 80–90% of [β‐11C]styrene and a specific radioactivity, of 100MBq/μmol. In a typical experiment starting with 960 MBq 11C‐methyl iodide, 200 MBq of [β‐11C]styrene was obtained within 42 min.
Synthesis of 1‐[4‐[3‐(N‐methyl N‐[3,4‐dimethoxy β‐phenethyl]amino] [3‐14C]propyloxy] benzenesulfonyl]‐2‐isopropyl indolizine or [14C]SR 33557
Authors: Demotte R. , Deblaton M. , Winand M. , Callaert M. , Sion R. , Gubin J. , Chatelain P.
Published: October 2006

[14C]SR 33557 was synthesized in six steps and in an overall yield of 3.8% from sodium [14C]cyanide.
Synthesis of 1,3,5‐trimethoxy[1‐14C]benzene
Authors: Lee Helen T. , Travalent Annette M. , Woo Peter W. K.
Published: October 2006

Utilizing the facile acylative annulation of 2‐methoxypropene with [1‐14C]malonyl dichloride (5), the synthesis of 1,3,5‐trimethoxy[1‐14C]benzene (8) was accomplished through a seven‐step sequence starting from potassium [14C]cyanide with an overall yield of 60%.

Thus, reaction of bromoacetic acid with potassium [14C]cyanide gave sodium [14C]cyanoacetate (1). Hydrolysis of 1 with sodium hydroxide solution provided the sodium salt of [1‐14C]malonic acid (2). Treatment of 2 with calcium chloride gave the calcium salt 3, which was acidified with concentrated sulfuric acid in ether to give [1‐14C]malonic acid (4). Reaction of 4 with oxalyl chloride in refluxing ether gave [1‐14C]malonyl dichloride (5). Annulative acylations of 2‐methoxypropene with 5 gave the crucial intermediate 5‐methoxy[1‐14C]resorcinol (7), together with 4‐hydroxy‐6‐methyl‐[2 (or 4)‐14C]2H‐pyran‐2‐one (6), in a ratio of 3: 1. However, 6 could be advantageously converted to 7a by initial 0‐methylation with dimethyl sulfate, followed by rearrangement of the product, 4‐methoxy‐6‐methyl[2(or 4)‐14C]2H‐pyran‐2‐one (6a), upon treatment with sodium methoxide. Finally, bis‐0‐methylation of 7 and 7a with dimethyl sulfate in refluxing acetone gave the title compound 8.
Synthesis of [5,6‐3H2]CP‐88,818 (β‐[5,6‐3H2]tigogenin cellobioside)
Authors: McCarthy Peter A.
Published: October 2006

CP‐88,818 (β‐tigogenin cellobioside) is a novel hypocholesterolemic and anti‐atherosclerosis agent which acts by inhibiting the absorption of dietary and biliary cholesterol. While the exact mechanism of this inhibition is unclear, CP‐88,818 is believed to block cholesterol absorption without entering the body. In order to prove this hypothesis, radiolabelled CP‐88,818 was needed. Herein, we report the stereoselective synthesis of [5,6‐3H2]CP‐88,818 in four steps from diosgenin acetate.
Preparation of carbazole‐3,6‐d2 and carbazole‐1,3,6,8‐d4
Authors: Chestand Arthur , Yang Ling , Walter Robert I.
Published: October 2006

Carbazole‐3,6‐d2 and carbazole‐1,3,6,8‐d4 were prepared by reduction of the corresponding di‐ and tetrabromocarbazoles in alkaline ethanol with deuterium gas and Pd/C catalyst.
Synthesis of tritiated (S)‐10‐bromoacetamidomethylcamptothecin
Authors: Shu Arthur Y. L. , Jakas Dalia , Richard Heys J.
Published: October 2006

Tritiated (S)‐10‐bromoacetamidomethylcamptothecin was prepared starting from (S)‐10‐hydroxycamptothecin. The key step consisted of palladium catalyzed direct tritium exchange on the intermediate (S)‐10‐aminomethylcamptothecin. 3H NMR spectroscopy indicated the tritium label was located exclusively at the C‐5 position.
Synthesis of 2H labelled diasteromeric isoxazolidines by 1,3‐dipolar cycloadditions of nitrones to alkenes
Authors: Liguori Angelo , Mascaro Paolo , Sindona Giovanni , Uccella Nicola
Published: October 2006

Specifically labelled 2H isoxazolidine epimers have been synthesized from suitably labelled nitrones and styrenes by 1,3‐dipolar cycloaddition.
Synthesis of 10,15‐[13C2]‐squalene and ‐DL‐squalene oxide
Authors: Hoshino Tsutomu , Williams Howard J. , Shishido Kozo , Ian Scott A.
Published: October 2006

[3‐13C]‐Ethyl farnesoate was prepared by alkylating 3‐13C‐ethyl acetoacetate with geranyl bromide, followed by hydrolysis, decarboxylation and treatment with the anion of triethyl phosphonoacetate. The ester was reduced with LAH, brominated with CBr4/ϕ3P, and the farnesyl bromide coupled with CuI/Li‐pyrrolidine to produce [10,15‐13C2]‐squalene. Epoxidation was effected by treatment with NBS in aqueous THF, followed by K2CO3‐mediated HBr elimination. The overall yield of DL‐10,15‐[13C2]‐squalene‐2,3‐oxide was 1.6%.
Synthese radioactive de sels d'ammonium quaternaires d'hydroxy imino methyl‐2 OU‐4 pyridinium au moyen de la N‐methyl formanilide‐14C. I ‐ marquage du dichlorure d'(hydroxyimino méthyl (14c)‐2 pyridinyle)‐1 (aminocarbonyl‐4′ pyridinyle)‐1′ dimethyl éther ou hi‐6‐(14c); du dibromure de bis [hydroxyimino méthyl (14c)‐4 pyridinyle]‐1,3 propane ou tmb‐4‐(14c) et du dibromure d'(hydroxyimino méthyl (14c)‐4 pyridinyle)‐1 (méthyl‐3′ imidazolyle)‐3 propane ou pyrimidoxime‐(14C)
Authors: Nicolas C. , Madelmont J. C. , Maurizis J. C. , Garrigue H. , Meyniel J. M. , Demerseman P. , Sentenac‐Roumanou H. , Veyre A.
Published: October 2006

The 14C labelling of three compounds : HI‐6, TMB‐4 and pyrimidoxime is described from 14C‐formic acid, sodium salt. The compounds were prepared by lithiation and formylation with N‐methyl (14C)‐formanilide followed by introduction of the hydroxylamine moieties and alkylation of the pyridine. Radiochemical yields were, respectively, 24,5%, 30% and 30%.
A facile stereospecific synthesis of the [2H6]‐isopropyl‐labelled metoprolol enantiomers from (2r)‐ and (2S)‐glycidyl 3‐nitrobenzenesulfonate
Authors: Murthy Satya S. , Nelson Wendel L.
Published: October 2006

Enantiomers of metoprolol containing six deuterium atoms in the isopropyl methyl groups were prepared in two steps from the sodium salt of 4‐(2‐methoxyethyl)phenol (3) and the commercially available (2R)‐ and (2S)‐glycidyl 3‐nitrobenzenesulfonates [(2R)‐2 and (2S)‐2]. The resulting (2R)‐ and (2S)‐epoxides were opened using [2H6]‐isopropylamine. The enantiomeric excesses were 93 and 95% for the deuterated (2R)‐ and (2S)‐enantiomers of metoprolol [(2R)‐1 and (2S)‐1], respectively, as determined by chiral column HPLC.
Enzymatic preparation of 3H‐labeled β‐ureidoisobutyric acid and β‐aminoisobutyric acid from 3H‐thymidine
Authors: Shields Anthony F. , Kozell Laura
Published: October 2006

We have synthesized β‐aminoisobutyric acid (3‐amino‐2‐[3H]methyl‐propanoic acid) and β‐ureidoisobutyric acid (3‐[(aminocarbonyl)amino]‐2‐[3H]methyl‐propanoic acid) starting with [3]thymidine (1‐(2‐deoxy‐β‐D‐ribo‐furanosyl)‐5‐[3H]methyluracil). We have developed a simplified enzymatic preparation using a dialyzed supernatant of homogenized dog liver. The homogenate was incubated with [3H]thymidine (41 Ci/mmol) in the presence of NADPH, and β‐ureidopropionic acid. After extraction the supernatant was purified by HPLC.
Isotopically labelled compounds for hazardous waste site cleanup investigations: Part I. Synthesis of [phenyl‐U‐14C] labelled 2,4‐dinitro‐6‐sec‐butylphenol (dinoseb) and [phenyl‐U‐14C] labelled 4‐n‐propylphenol
Authors: Goszczynski Stefan , Crawford Ronald L.
Published: October 2006

The Fries rearrangement of [phenyl‐U‐14C] propionate forming a mixture of ortho and para hydroxypropiophenones was followed by steam distillation to separate the isomeric products. A Grignard addition to the ortho isomer and elimination of water from the intermediate carbinol, followed by hydrogenation and nitration, yielded [phenyl‐U‐14C] labelled dinoseb. A Wolff‐Kishner reduction of the para isomer furnished [phenyl‐U‐14C] 4‐n‐propylphenol.
The synthesis of 1,2‐dioleoyl‐sn‐[2‐3H]glycero‐3‐phosphoserine
Authors: Binaglia L. , Alunni‐Bistocchi G. , Orlando M. , Orlando P. , Rosa G. , Trenta R.
Published: October 2006

Phosphatidylserine labelled in the glycerol moiety was synthesized from [2‐3H]glycerol through enzymatic phosphorylation of glycerol, acylation of labelled sn‐glycerol‐3‐phosphate with oleic anhydride and condensation of phosphatidic acid with N‐t‐BOC serine benzhydryl ester. The product was chromatographically purified with an overall yield of 12%, at a molar specific activity of 25 Ci/mol.
Synthesis of 15N,15N‐imidazoleacetic acid
Authors: Prell George D.
Published: October 2006

15N,15N‐imidazoleacetic acid was synthesized from 15N, 15N‐DL‐histidine (>99 atom % 15N). The latter, oxidized with sodium hypochiorite, formed 15N,15N‐imidazoleacetonitrile. The free acid was prepared after acid hydrolysis of the nitrile, elution from an anion exchange column with acetic acid, then drying. Formation of by‐product(s), produced when other methods were used, and which may contaminate some commercial sources of imidazoleacetic acid, was avoided with this method.
Synthesis of aldose reductase inhibitor, 3,4‐dihydro‐4‐oxo‐3‐[[5‐(trifluoromethyl)‐214C benzothiazolyl]methyl]‐1‐phthalazineacetic acid
Authors: Mylari Banavara L. , Zembrowski William J.
Published: October 2006

Synthesis of the title compound, C14 labeled CP‐73,850 (zopolrestat), was accomplished by condensation of 1‐phthalazineacetic acid, 3,‐14C cyanomethyl‐3,4‐dihydro‐4‐oxo‐, ethyl ester with 3‐amino‐4‐mercapto‐benzotrifluoride, followed by base hydrolysis of the resultant product, 1‐phthalazineacetic acid, 3,4‐dihydro‐4‐oxo‐3‐[[5‐trifluoromethyl)‐2‐benzothiazolyl]14C methyl]‐3,4‐dihydro‐4‐oxo‐, ethyl ester.
Synthesis of novel tritium labeled oxamyristic acids
Authors: Devadas Balekudru , Adams Steven P. , Gordon Jeffrey I.
Published: October 2006

Syntheses of [3H]‐labeled 13‐oxa (5) and 6‐oxa (9) myristic acids with specific activity of 137 Ci/mmol and 105 Ci/mmol respectively, starting from the corresponding acetylenic precursors, 12‐methoxy‐10‐dodecynoic acid (4) and 5‐(3‐octynyloxy)pentanoic acid (8) are described. The precursor 4 is readily obtained in high yield by alkylation of the lithium salt of methyl propargyl ether with 9‐iodononanoic acid, whereas 8 is obtained by alkylation of 3‐octyn‐1‐ol with t‐butyl‐5‐bromovalerate under phase transfer conditions, followed by acid catalysed removal of the t‐butyl group.
Synthesis of two 14C‐labelled catechol‐O‐methyltransferase inhibitors
Authors: Karlsson Carita , Honkanen Erkki
Published: October 2006

14C‐labelled 3‐(3, 4‐dihydroxy‐5‐nitrophenylmethylidene)‐2,4‐pentanedione (4) and 14C‐labelled E‐N, N‐diethyl‐2‐cyano‐3‐(3,4‐dihydroxy‐ 5‐nitrophenyl)acrylamide (5) have been synthesized from [carbonyl‐14C]vanillin.
A convenient synthesis of 14C‐cotinine from 14C‐nicotine
Authors: Desai Dhimant H. , Djordjevic Mirjana V. , Amin Shantu
Published: October 2006

A convenient synthesis with analytical monitoring of 14C‐cotinine is reported. 14C‐Nicotine was converted into 14C‐dibromocotinine hydrobromide perbromide. Debromination, achieved by using Zn dust/acetic acid, resulted in high yields (71%) of 14C‐cotinine.
Synthesis of 3,5‐diisopropyl[carboxy‐14C]salicylic acid and its 67CU complex
Authors: Chidambaram Mankulathu V. , Epperson Claude E. , Williams Skip , Gray Ronda A. , Sorenson John R. J.
Published: October 2006

The synthesis of 3,5‐diisopropyl[carboxy‐14C]salicylic acid was achieved via Kolbe‐Schmitt carboxylation of potassium 2,4‐diisopropylphenolate. The yield of this acid was 81% based upon the weight of the product and 93% based upon radioactivity incorporated into the labeled acid which contains 98% 14C in the carboxyl group (specific activity = 5.1 μCi/mg). The labeled acid was characterized by ultraviolet spectrophotometry and purity established by thin‐layer chromatography, autoradiography, and liquid scintillation counting. A 90% yield of the double labeled 14C, 67Cu‐complex (specific activity = 4.6 μC/mg) was obtained using conditions developed with non‐radioactive reactants. The presence of 67Cu in this complex was established using γ‐ray emission spectrophometry.
Specific tritium labelling of sphingosines at the 3‐position
Authors: Birk Rolf , Brenner–Weiß Gerald , Giannis Atanassios , Sandhoff Konrad , Schmidt Richard R.
Published: October 2006

Azidosphingosines 4A,B are transformed with DDQ into the corresponding keto derivatives 6A,B. Reduction of the keto group with [3H]NaBH4 and then conversion of the azido group into the amino group by Staudinger reaction yields stereoselectively the D‐erythro‐and L‐threo‐sphingosines 9A,B, 10A,B, respectively.
Synthesis of the enantiomers of 3‐deuterium labelled lactic acid
Authors: Sanière Michèle , Hafa Hassane El , le Merrer Yves , Depezay Jean Claude , Rocchiccioli Francis
Published: October 2006

Both R‐ and S‐ enantiomers of 3‐monodeuterated lactic acid ([3‐2H]‐2(R) and 2(S)‐hydroxypropanoic acids) were synthesized by regiospecific nucleophilic opening of diastereoisomer epoxides derived from D‐mannitol, with lithium aluminium deuteride. Spectroscopic analysis of the product shows a complete deutero‐incorporation which makes [3‐2H]‐lactic acid suitable as an internal standard using gas chromatography‐mass spectroscopy.
Synthesis of deuterium labelled cocaine and pseudococaine
Authors: Casale J. F. , Lewin A. H. , Raney H. T. , Cooper D. A.
Published: October 2006

Cocaine and pseudococaine were mass‐labelled with deuterium at various positions on the tropane ring. The synthetic procedures followed were adaptations of those previously published for the unlabelled compounds. The isotopic purity was greater than 95% for 2‐[2H]–, 4,4‐[2H2]‐, and 1,5,6,6,7,7‐[2H6]‐cocaine and 3‐ [2H]‐, 4,4‐[2H2]‐, and 1,5,6,6,7,7‐[2H6]‐pseudococaine, while that of 3‐[2H]‐cocaine exceeded 90%.
Synthesis and characterization of optically pure [3H](+)azidophenazocine ([3H](+)‐AZPH), a novel photoaffinity label for sigma receptors
Authors: de Costa Brian R. , Bowen Wayne D.
Published: October 2006

[3H](+)‐cis‐N‐(2‐(4‐Azidophenyl)ethyl) ‐2′‐hydroxy‐2,6‐dimethyl‐6,7‐benzomorphan ([3H]1) ([3H](+)‐AZPH), a novel high affinity and high selectivity benzomorphan based photoaffinity label for sigma receptors was synthesized in 4 steps starting with optically pure (+)‐normetazocine and 2‐(p‐azidophenyl)ethyl methanesulfonate ester. Condensation of these compounds in DMF in the presence of NaHCO3 afforded 1 in 77% yield. The tritiation precursor (+)‐cis‐N‐(2‐(4‐azidophenyl)ethyl)‐2′‐hydroxy‐1′,3′‐dibromo‐2,6‐dimethyl‐6,7‐ benzomorphan (4) for medium specific activity [3H]1 was obtained in 96% yield by bromination of 1 with 2 equivalents of bromine. The sequence of catalytic tritiation of 4, treatment of the resulting aniline ([3H]5) (13.5% radiochemical yield, specific activity 22.9 Ci/mmol) with nitrous acid followed by sodium azide afforded the target compound in 78% chemical yield.
Synthesis of [2‐14C]‐2′‐deoxycytidine‐3N‐cyanoborane
Authors: Burnham Bruce S. , Wyrick Steven D. , Hall Iris H. , Sood Anup , Spielvogel Bernard F.
Published: October 2006

Synthetic nucleosides (e.g., 5‐fluorouracil, 6‐mercaptopurine) are used extensively as antineoplastic drugs. Recent research in boron chemistry has lead to the development of a series of amine‐boranes that possess significant antineoplastic activity. The agents may also be useful in boron neutron capture therapy (BNCT), therefore giving the compounds a dual mechanism of cytotoxic action. Herein is a report of the synthesis of one of the more active boronated nucleosides, 2′‐deoxycytidine‐3N‐cyanoborane with a 14C‐label in the 2‐position of the pyrimidine ring.
Syntheses of tritium and carbon‐14 labelled N‐ (3‐dimethyl aminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)ergoline‐8β‐carboxamide (cabergoline), a potent long lasting prolactin lowering agent
Authors: Mantegani Sergio , Brambilla Enzo , Ermoli Antonella , Fontana Erminia , Angiuli Patrizia , Vicario Gian Piero
Published: October 2006

The syntheses of 3H‐ and 14C‐labelled cabergoline (FCE 21336), namely N‐(3‐dimethylaminopropyl)‐N‐(ethylamino‐carbonyl)‐6‐(2‐propenyl)ergoline‐8 β ‐carboxamide 1 and its analogues are described.

Tritiated cabergoline ([3H]cabergoline) 6, namely N‐(3‐dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐ [2,3‐3H]‐propenyl)ergoline‐8β‐carboxamide, was obtained, by catalytic reduction with tritium gas, according to two different synthetic procedures:

‐ a three step route, starting from 6‐(2‐propargyl)‐dihydro lysergic acid‐methyl ester 3 gave [3H]cabergoline, 97% radiochemically pure, with a specific radioactivity of 11.19 GBq/mmol and in an overall radiochemical yield of 3.5%.

‐ a one step route, starting from 1‐ethyl‐3‐(3‐dimethyl‐aminopropyl)‐3‐6′‐(2‐propargyl)ergoline‐8′β‐ carbonyflurea 5′ yielded [3H]cabergoline with a radiochemical purity >97%, specific radioactivity 1.06 TBq/mmol and radiochemical yield of 23%.

A modification of this last procedure also gave [3H]dihydro cabergoline ([3H]FCE 23411), namely N‐(3‐dimethylaminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐[2,3‐3H]propyl)ergoline‐8β‐carboxamide 7, 97% radiochemically pure and with a specific radioactivity up to 4.03 TBq/mmol.

The synthesis of [14C]cabergoline was carried out, in a three step route, by addition of potassium[14C]cyanide to 6‐(2‐propenyl)‐8β‐chloroergoline 12 to give the expected N‐(dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)‐ergoline‐8β‐ [14C]carboxamide 15′, 97% radiochemically pure with a specific radioactivity of 2.09 GBq/mmol and an overall radiochemical yield of 16%.
Synthesis of [10,10,10‐2H3]geranyl diphosphate
Authors: Izumi Shunsuke , Aihara Mie , Hiraga Yoshikazu , Hirata Toshifumi , Suga Takayuki
Published: October 2006

[10,10,10‐2H3]‐3, 7‐Dimethyl‐2(E), 6‐octadienyl diphosphate ([10,10,10‐2H3]geranyl diphosphate) was synthesized from 6‐(benzyloxy)‐4‐methyl‐4(E)‐hexenal by regioselective deuteration involving a modified Wittig reaction as the key step.