bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 14C or 3H‐labelled indometacin farnesil (E‐0710)
Authors: Abe Shinya , Yamatsu Isao , Yamato Chihiro , Kobayashi Seiichi , Mishima Mannen
Published: October 2006

A 14C or 3H‐labelled, 7:3 (2E:2Z) isomeric mixture of 6E‐3, 7, 11‐trimethyl‐2, 6, 10‐dodecatrienyl‐1‐(p‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate (indometacin farnesil; IMF), a prodrug of indomethacin, was synthesized in order to study the pharmacokinetic profiles of this drug. Esterification of a 7:3 (2E:2Z) isomeric mixture of 6E‐3, 7, 11‐trimethyl‐2, 6, 10‐dodecatrienol [farnesol (3)] with [2‐14C] indomethacin [14C‐IND (1)] or [G‐3H] indomethacin [3H‐IND (2)] gave the corresponding 14C or 3H‐labelled indometacin farnesil [14C‐IMF (4) or 3H‐IMF (5)]. On the otherhand, [3‐14C] 6E‐3, 7, 11‐trimethyl‐2, 6, 10‐dodecatrienol [14C‐F (8)] which was obtained from [2‐14C] 5E‐6, 10‐dimethylundeca‐5, 9‐dien‐2‐one [14C‐geranyl acetone (7)] in two steps, was esterified with indomethacin to give farnesyl moiety 14C‐labelled indometacin farnesil 14C‐F‐IMF (6) 1.
The synthesis of (5R)‐ and (5S)‐[5‐3H]‐L‐ornithine
Authors: Parry Ronald J. , Ju Shyhchen , Baker Bill J.
Published: October 2006

A practical synthesis of (5R)‐ and (5S)‐[5‐3H]‐L‐ornithine is described. The key steps in the synthesis are the reduction of [formyl‐3H]‐5‐hexenal with S‐ or R‐Alpine Borane to (1R)‐ and (1S)‐ [1‐3H]‐5‐hexen‐1‐ol and the use of the Evans electrophilic azidation of chiral imide enolates to introduce the α‐amino group of ornithine. The stereochemistry expected for the Alpine Borane reduction was verified by NMR analysis of the camphanate ester derived from reduction of [formyl‐2H]‐5‐hexenal with R‐Alpine Borane.
A short synthesis and its application to the preparation of radio labelled leukotriene inhibitor Sch 37224
Authors: Duelfer T. , Gala D.
Published: October 2006

A new, short synthesis of 1‐(1,2‐dihydro‐4‐hydroxy‐1‐phenyl‐2‐oxo‐1,8‐naphthyridin‐3‐yl)‐pyrrolidinium hydroxide, inner salt, 1, was achieved by condensing methyl 2‐phenylamino‐3‐pyridine carboxylate 2 with ethyl 1‐pyrrolidine acetate 4. This gave highly pure product in 60% yield. This synthesis was applied to the preparation of 14C labelled 1. Radiolabelled 1 was synthesized from u‐[14C]‐aniline in three steps at 97% radiochemical purity and 27.3% radiochemical yield.
Synthesis of (Z)‐3‐[4‐(acetyloxy)‐5‐ethyl‐3‐methoxy‐1‐NAPH‐thalenyl]‐2‐methyl‐2‐ propenoic‐2‐14C acid (14C‐E5090)
Authors: Tanaka Masayuki , Sakurai Hideki , Yoshimura Tsutomu
Published: October 2006

(Z)‐3‐[4‐(Acetyloxy)‐5‐ethyl‐3‐methoxy‐1‐naphthalenyl]‐2‐methyl‐2‐propenoic‐2‐14C acid 7 (14C‐E5090) was synthesized in order to study the pharmacokinetic profile of E5090, an orally active inhibitor of IL‐1 generation. 14C‐E5090 with a specific activity of 43.34mCi/mmol was prepared in 5 steps in 12.9% overall yield from 5‐ethyl‐3‐methoxy‐4‐methoxymethoxy‐1‐naphthalenecarbaldehyde 1.
Synthesis of [14C]‐labelled eicosa‐5,8,11‐triynoic acid and conversion to anti‐inflammatory amides
Authors: Pilgrim W. R. , Nedoncelle P. , Shroot B. , Maignan J. , Restlé S. , L'Oréal
Published: October 2006

A four step synthesis of [5,6‐14C]‐eicosa‐5,8,11‐triynoic acid (1) from [14C]‐labelled acetylene is described. [14C2]‐acetylene was converted to 5‐chloro‐[1,2‐14C]‐pentyne via reaction of its monolithium salt with 3‐bromo‐1‐chloropropane. The doubly labelled 5‐chloropentyne thus obtained was transformed to [5,6‐14C]‐hex‐5‐ynoic acid which was then coupled with 1‐chloro‐tetradeca‐2,5‐diyne to give the title compound. Using 2‐(2‐aminoethoxy)ethanol and 1‐(2‐hydroxyethyl)piperazine, amides (2) and (3), which had previously been found to be potent inhibitors of the 5‐lipoxygenase enzyme, were prepared from [14C]‐labelled eicosatriynoic acid by way of acylimidazole chemistry.
Synthesis of tritium labelled 5,6‐dihydro‐7‐(1H‐imidazol‐1‐YL)‐naphthalene‐2‐carboxylic acid (FCE 22178), a new thromboxane synthetase inhibitor
Authors: Fontana Erminia , Vicario Gian Piero
Published: October 2006

Synthesis of [3H]FCE 22178, namely 5,6‐dihydro‐7‐(1H‐[G‐3H]imidazol‐1‐yl)‐naphthalene‐2‐carboxylic acid 5 was performed in three steps from 5,6,7,8‐tetrahydro‐8‐hydroxy‐7‐(1H‐imidazol‐1‐yl)‐naphtalene‐2‐carboxylic acid 2 by bromination, catalytic tritiation and final dehydration, in an overall radiochemical yield of 48%. The product was 97% radiochemically pure and had a specific radioactivity of 9.15 GBq/mmol.
Synthesis of tritium labeled MK‐886, a leukotriene biosynthesis inhibitor; employment of epibromohydrin as a masked electrophilic acetone synthon
Authors: Schmidt Stanley J. , Garnes Keith T. , Heys J. Richard , Landvatter Scott W. , Adams Jerry L.
Published: October 2006

1‐(4‐Chloro‐[3‐3H]benzyl) ‐3‐(t‐butylthio)‐a, a‐dimethyl‐5‐(i‐propyl) ‐indole‐2‐propanoic acid (10, MK‐886) was prepared by catalytic tritium/halogen exchange on 1‐(4‐chloro‐3‐iodobenzyl)‐3‐(t‐butylthio)‐a,a ‐dimethyl‐5‐(i‐propyl)‐indole‐2‐propanoic acid (9). Compound 9 was prepared by a synthesis converging at the indole benzylation step. The required indole 4 was prepared by means of a Fischer indole synthesis employing the highly functionalized unsymmetrical ketone 3. Ketone 3 was efficiently made in three steps using epibromohydrin as a masked electrophilic acetone synthon. The halogenated benzyl bromide moiety 7 was prepared in three steps from 1‐chloro‐2‐iodo‐4‐(trifluoromethyl)‐benzene.
An expedient synthesis of high specific activity tritium labelled 4‐fluoro‐1‐[1‐(2‐thienyl)]cyclohexylpiperidine ([3H]FTCP), a ligand for further characterization of the phencyclidine/NMDA receptor complex
Authors: Grayson Neile A. , de Costa Brian R. , Linders Joannes T. M. , Rice Kenner C.
Published: October 2006

[18F]4‐Fluoro‐1‐[1‐(2‐thienyl)cyclohexyl)]piperidine is a ligand potentially useful for positron emission tomography of the PCP/NMDA receptor complex in the mammalian brain. The tritium‐labelled title compound was synthesized in 5 steps starting with cyclohexanone. Catalytic tritiolysis in the final step afforded the title compound in high radiochemical yield and specific activity. This method represents a more efficient approach than previously published syntheses.
Syntheses of 3H‐ and 2H‐labeled (17R)‐17,20‐dimethyl‐7‐thiaprostaglandin E1 methyl ester
Authors: Tanaka Toshio , Bannai Kiyoshi , Manabe Kenji , Kurozumi Seizi
Published: October 2006

The syntheses of [19,20‐3H2]‐ and [3,3,4,4,5,5,6,6‐2H8]‐(17R)‐ 17,20‐dimethyl‐7‐thiaprostaglandin E1 methyl esters (3 and 5) are described. The di‐tritiated compound 3 was prepared from its protected (Z)‐Δ 19‐precursor (21) via catalytic reduction with tritium gas having a specific activity of 49 Ci / mmol. The octa‐deuterated compound 5 was prepared from tetrahydrofuran‐d8.
Synthesis of S‐ribosyl‐L‐homocysteine specifically tritiated at the 5‐C position
Authors: Guillerm G. , Allart B.
Published: October 2006

S‐Ribosyl‐L‐homocysteine, tritiated specifically at the 5‐C position, has been synthesized in order to assay S‐Ribosyl‐L‐homocysteine hydrolase (EC. 3.3.1.3).
14C‐labeling of a novel carbapenem antibiotic SM‐7338
Authors: Nishioka Kazuhiko , Kanamaru Hiroshi
Published: October 2006

(1R,5S,6S)‐2‐ [(3S,5S)‐5‐Dimethylaminocarbonylpyrrolidin‐3‐ylthio]‐6‐ [(1R)‐1‐hydroxyethyl]‐1‐methylcarbapen‐2‐em‐3‐carboxylic acid trihydrate (SM‐7338), a novel 1 β‐methyl carbapenem antibiotic, was labeled with carbon‐14 at the C3 position of the carbapenem nucleus for use in metabolic studies. The synthesis was achieved according to the scheme illustrated in Fig. 3. Selective esterification of [2‐14C]malonic acid (2) with 4‐nitrobenzyl bromide (3) gave its monoester (4). Condensation of the magnesium salt of 4 with the imidazolide derived from the azetidinone carboxylic acid (5) provided the β‐keto ester (6), which was desililated with hydrochloric acid to give the alcohol (7). Treatment of 7 with carboxybenzenesulfonyl azide followed by decomposition of the resulting diazo intermediate (8) in the presence of a rhodium catalyst produced the bicyclic keto ester (9). Reaction of 9 with diphenyl chlorophosphate in the presence of N,N‐diisopropylethylamine and subsequent displacement reaction of the vinyl phosphate (10) with mercaptopyrrolidine (11) gave bis‐protected SM‐7338 (12). Catalytic hydrogenolysis of 12 afforded [carbapenem‐3‐14C]‐SM‐7338 (1). The overall yield of 1 was 5.8% from 2.
Chiral synthesis of L‐[14C]phenylalanine and its incorporation into the renin inhibitor PD 132002
Authors: Lee Helen T. , Hicks James L. , Johnson Donald R.
Published: October 2006

[1S‐(1R*,2S*,3R*)]‐3‐[[1‐(Cyclohexylmethyl)‐2,3‐dihydroxy‐5‐methylhexyl]‐amino]‐N‐[N‐(4‐morpholinosulfonyl)‐L‐ phenylalanyl]‐3‐oxo‐DL‐alanine methyl ester (PD 132002) was found to be a renin inhibitor and thus potentially useful for the treatment of hypertension. This peptidomimetic agent contains an L‐phenylalanine residue which was chosen as the site for carbon‐14 incorporation. The chiral synthesis using (4S)‐4‐(phenylmethyl)‐2‐oxazolidinone as a chiral auxiliary for asymmetric hydrazide formation was modified to make it amenable to carbon‐14 synthesis.

L‐[1‐14C]Phenylalanine was synthesized in seven steps from 14CO2 in an overall yield of 33%. It was further converted to [14C]PD 132002 in three more steps with an overall yield of 4.95%. The final specific activity was 35.5 mCi/mmol.
Synthesis of tritium labelled TRH‐like peptides using asymmetric anhydride coupling
Authors: Bílek R. , Bradbury A. F. , Smyth D. G.
Published: October 2006

A method is presented for the preparation of [3H]‐labelled TRH‐like tripeptides. The synthesis involves preparation of the appropriate dipeptide by the solid phase procedure using Fmoc‐protection and the [3H]‐labelled pyroglutamic acid is then coupled as a mixed anhydride with Fmoc‐phenylalanine. Conditions suitable for the conversion of [3H]‐glutamine to [3H]‐pyroglutamic acid are also described. The [3H]‐labelled tripeptides are obtained in a high state of purity and with efficient incorporation of radiolabel.
An improved synthetic procedure for the preparation of 195mPt labelled anti‐tumour complexes
Authors: Jackson H. , McAuliffe C. A. , Perera A. , Sharma H. L. , Tinker N. J.
Published: October 2006

An improved synthetic procedure for the preparation of high specific activity 195mPt labelled cisplatin, carboplatin and iproplatin is reported. The procedure involves synthetic strategies which optimise the yields at each stage of the synthesis, giving products of high purity and in high yield (ie. cisplatin and carboplatin, 43%, and iproplatin, 22%). A new procedure for the synthesis of carboplatin using silver 1,1‐cyclobutanedicarboxylate is also reported.
Synthesis of labeled (10R)‐Juvenile hormone III bisepoxide, and its photoaffinity analog, [12‐3H]‐(10R)‐6,7,10,11‐bisepoxyfarnesyl diazoacetate (BEFDA)
Authors: Latli Bachir , Prestwich Glenn D.
Published: October 2006

Radiolabeled optically‐active JH III bisepoxide ([3H]‐(10R)‐JHB3) was synthesized from [12‐3H] (10R)‐JH III using dimethyldioxirane to give an inseparable mixture of diastereomers with the trans‐6,7‐epoxide syn or anti to the existing 10,11‐epoxide. [3H]‐(10R)‐JHB3 (or the unlabeled material) was converted in three steps to the corresponding (10R)‐6,7,10,11‐bisepoxyfarnesyl diazoacetate (BEFDA), a photoaffinity label for JHB3 receptors and binding proteins.
Synthesis of tritium labeled musk xylene, [3H] 5‐tert‐butyl‐2,4,6‐trinitro‐m‐xylene
Authors: Fukuoka Masamichi , Nambaru Seiichi , Tanaka Akira
Published: October 2006

Synthesis of 3H‐musk xylene (MX) was carried out by two schemes. Nitration of 3H‐5‐tert‐butyl‐m‐xylene (3) decreased in the 3H‐incorporation ratio. Reduction of MX‐bromide (6) with NaB3H4 gave the highly labeled MX (8) and another bromide (7) gave 9 with tritium atom produced by equilibration between NaB3H4 and H2O or between NaBH4 and 3H2O.
Use of 2‐dimethylaminopyridine in tritium and deuterium exchange reactions
Authors: Reddy Guvvala N. , Soares Christopher J. , Kurth Mark J. , Segall Hank J.
Published: October 2006

Advantages of 2‐dimethylaminopyridine as base in isotope exchange reactions that occur via enol formation are described for the preparation of deuterium and tritium labeled hexanal.
A simple synthesis of [1,3‐13C2]4‐(2,6,6‐trimethylcyclohexen‐1‐yl)buten‐2‐one (ß‐ionone)
Authors: Curley Robert W. , Blust Michael A. , Humphries Keith A.
Published: October 2006

A convenient, one‐step synthesis of doubly 13C‐labelled ß‐ionone was accomplished by aqueous sodium hydroxide catalyzed aldol condensation of 1,3‐13C2‐acetone with the recently commercially available ß‐cyclocitral. This retinol‐like compound obtained in ca. 60% yield, should prove useful in NMR studies of retinoid binding to its transport proteins.
Tritium labelling of polyols
Authors: Akulov G. P. , Snetkova E. V. , Kaminski Ju. L. , Kudelin B. K. , Efimova V. L.
Published: October 2006

Mannitol, galactitol and myo‐inositol were labelled by a solid state isotope exchange with gaseous tritium. The labelled polyois were prepared with specific activities in the range 740–4440 TBq/mol (20–120 kCi/mol) after purification by HPLC.
The synthesis of tritium‐labelled alanine by solid‐state catalytic reactions
Authors: Yu. A. Zolotarev , Kozik V. S. , Dorokhova E. M. , Tatur V. Yu. , Rosenberg S. G. , Myasoedov N. F.
Published: October 2006

The solid‐state catalytic hydrogenation (SCH) of unsaturated precursor compound and the high‐temperature solid‐state catalytic isotope exchange (HSCIE) showed that the total incorporation of isotope and its distribution between the α‐and β‐positions of the alanine molecule can be modified by changing the temperature of solid state reactions. Tritium incorporation at high‐temperatures proceeds in a manner which retains the configuration of the asymmetric α‐carbone atom. 3H NMR analysis of tritiated isotopomers was used for the investigation of solid‐state reactions. The HSCIE reaction proceeds selectively at 140 °C and only part of the molecules is in the the tritium spillover reaction zone. At 220°C HSCIE proceeds evenly along the whole mass to give uniformly labelled alanine.
Synthesis of the cardiotonic agent 14C‐loprinone.
Authors: Yamanaka Motosuke , Suda Shinji , Tadano Kyoichi
Published: October 2006

14C‐Labeled 1,2‐dihydro‐5‐imidazo [1,2‐a]pyridin‐6‐yl‐6‐methyl‐2‐oxo‐3‐pyridinecarbonitrile hydrochloride monohydrate 6 was synthesized in 5 steps from 6‐bromoimidazo [1,2‐a] pyridine using [2‐14C] cyanoacetamide as the source of the radiolabel. The key intermediate, 1‐imidazo [1,2‐a] pyridin‐6‐yl‐2‐propanone 3 was prepared by the selective ozonolysis of the propenyl group of 6‐(2‐methylpropen‐3‐yl) imidazo [1,2‐a] pyridine 2 under acidic conditions followed by the reduction with sodium sulfite. The chemical yield of 6 from 4‐dimethylamino‐3‐imidazo‐[1,2‐a]pyridin‐6‐yl‐3‐buten‐2‐one 4 and the radiochemical yield from [2‐14C] cyanoacetamide were both 57%. The radiochemical purity and the specific activity of 6 were 98% and 1868.5 MBq/mmol, respectively.
Synthesis of (±)‐[1,1′‐15N2, 2′‐13C]‐trans‐3′‐methylnicotine
Authors: Sirimanne Sarath R. , Maggio Vincent L. , Patterson Donald G.
Published: October 2006

The synthesis of (±)‐[1,1′‐15N2, 2′‐13C]‐trans‐3′‐methylnicotine is reported.15N‐3‐Bromopyridine obtained from bromination of pyridine was formulated with nBuLi/[carbonyl‐13C]‐methyl formate. The resulting15N‐Pyridine‐3‐[13C‐carbonyl]‐carboxaldehyde was reacted with15N‐methylamine and then the resulting Schiff's base was condensed with succinic anhydride to give (±)‐[1,1′‐15N2, 5′‐13C]‐trans‐4′‐carboxycotinine. Reduction with lithium aluminium hydride and mesylation followed by reduction with Zn/Nal gave (±)‐[1,1′‐15N2, 2′‐13C]‐trans‐3′‐methylnicotine.
Radio‐ and fluorescence‐labelling of thapsigargin, a selective inhibitor of microsomal calcium‐ATPase
Authors: Andersen Annette , Lauridsen Annette , Br Christensen S. ØGger
Published: October 2006

Debutanoylthapsigargin (2) labelled in the skeleton was prepared by stereoselective reduction of the ketone (3) obtained by oxidation of debutanoylthapsigargin. Butanoylation of 2 yielded thapsigargin 1. The use of sodium boro[3H]hydride as a reducing agent afforded labelled debutanoylthapsigargin with a specific activity of 22 Ci/mmol.

A fluorescent analogue of thapsigargin (4a) was prepared by allowing 2 to react with N‐dansyl‐β‐alanine. Acetylation of 4a afforded a trisacetate (4c) the missing bioactivity of which allows it to be used as a negative control.
Synthesis and binding to striatal membranes of no carrier added I‐123 labeled 4′‐iodococaine.
Authors: Metwally S. A. M. , Gatley S. J. , Wolf A. P. , Yu D.‐W.
Published: October 2006

An 123I labeled cocaine analog, 4′‐[123I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases.
Preparation of tritium‐labelled dextran and inulin
Authors: Akulov G. P. , Kaminski Ju. L. , Korsakova N. A. , Kudelin B. K.
Published: October 2006

Tritiated dextran and inulin were prepared by both a catalytic solid state and a liquid phase isotope exchange with gaseous tritium. The liquid phase procedure is convenient for preparation of the polysaccharides with specific activities up to 5 mCi/g, while the solid state procedure allows specific activities up to 700 mCi/g.
Synthesis of [14C]‐labeled N‐tert‐butyl‐α‐phenylnitrone. A potential spin‐trapping agent
Authors: Angelini G. , Carnevaletti F. , Piccinini F.
Published: October 2006

A single step synthesis of the [14C‐ring]‐N‐tert‐butyl‐α‐phenylnitrone (1) starting from the [14C‐ring] benzaldehyde is described. The product is obtained in high yield (90%) with a good level of purity.
A high yield microscale enzymatic synthesis and purification Of 14C‐Labeled Nicotinamide Adenine Dinucleotide Phosphate (NADP+)
Authors: Ronneberg Andre , Metz Gordon , Weld Richard , Roffey Peter , Craney Chris
Published: October 2006

Uniformly labeled (U) 14C nicotinamide adenine dinucleotide phosphate (NADP+) was synthesized by phosphorylating [U‐14C]nicotinamide adenine dinucleotide (NAD+) in the presence of immobilized NAD+ kinase. The 15 μCi (600 μL) synthesis consistently achieved yields between 80% and radiochemical purities greater than 95%. The [U‐14C]NADP+ was purified by high performance anion‐exchange chromatography using a gradient elution of ammonium bicarbonate. This procedure may be applicable to the synthesis of other charged, UV‐absorbing products of enzyme‐catalyzed reactions.
The synthesis of [14C]pantoprazole ‐ SK&F 96022Z. An H+/K+ ATPase inhibitor
Authors: Crowe A. M , Johnston C. E. A , Lawrie K. W. M , Saunders D
Published: October 2006

Pantoprazole 1, SK & F 96022Z, an H+/K+ ATPase inhibitor has been prepared, radiolabelled with carbon‐14, in two positions, for drug metabolism studies. [Benzimidazole‐2‐14C]Pantoprazole in 4 steps from potassium ethyl [14C]xanthate, and [pyridylmethyl‐14C]pantoprazole from cuprous [14C]cyanide in 8 steps. The overall radiochemical yields of these syntheses were 37.9% and 5.2% respectively.
An efficient method for synthesizing [d6]‐butadiene monoepoxide
Authors: Maples Kirk R. , Lane Jennifer L. , Dahl Alan R.
Published: October 2006

Epoxides are known mutagenic and carcinogenic metabolites of alkenes. During current toxicological investigations in our laboratory, we have monitored in vivo epoxide levels using gas chromatography/mass spectroscopy isotope dilution assays. These assays require the use of deuterated analogues for the expected epoxide metabolites. To determine whether butadiene monoepoxide is formed in vivo following inhalation of 1,3‐butadiene, deuterated butadiene monoepoxide, a compound that is not commercially available, was needed. To meet this need, we developed a method using monoperoxyphthalic acid to synthesize [d6]‐butadiene monoepoxide from [d6]‐1,3‐butadiene with a reaction time of 50 min and a 94% yield.
Synthesis of some useful tritium labelled auxins
Authors: Buchman O. , Pri‐Bar I. , Shimoni M. , Azran J.
Published: October 2006

The synthesis of six useful auxins labelled with tritium is described. The following compounds were prepared: 3‐indoleacetic acid‐5‐3H (28.9 Ci‐1.07 TBq/mmol), 3‐indolebutyric acid‐5‐3H (7.3 Ci‐270 GBq/mmol), 1‐naphthylacetic acid‐4‐3H (27.6 Ci‐1.02 TBq/mmol), 2,4‐dichlorophenoxyacetic acid‐5‐3H (18.5 Ci‐685 GBq/mmol), 2(2,4‐dichlorophenoxy‐5‐3H)‐propionic acid (20.7 Ci‐766 GBq/mmol), 2(2,4‐dichlorophenoxy)‐propionic acid‐3‐3H (0.39 Ci‐14.4 GBq/mmol), and 4‐chlorophenoxyacetic acid‐2‐3H (13.3 Ci‐492 GBq/mmol).
Synthesis of iodobuprenorphine for use in radioimmunoassay
Authors: Debrabandere L. , van Boven M. , Daenens P.
Published: October 2006

The synthesis of [125I]iodobuprenorphine is described. This compound has been used as a tracer molecule in the development of a new radioimmunoassay for buprenorphine. The parameters that effect the direct iodination of buprenorphine using sodium [127I]iodide, in the presence of either chloramine‐T or Iodo‐Beads®, were previously studied. The structure of iodobuprenorphine was confirmed by mass spectrometry.
Synthesis of [14C]‐N‐[(trimethylamineboryl) carbonyl]‐phenylalanine‐methyl ester
Authors: Miller Merrill C. , Wyrick Steven D. , Hall Iris H. , Sood Anup , Spielvogel Bernard F.
Published: October 2006

Reported is the synthesis of [14C]‐L‐N‐[(trimethylamineboryl)carbonyl]‐phenylalanine methyl ester, a boron containing α‐amino acid dipeptide analog with anti‐neoplastic, anti‐inflammatory, and hypolipidemic activities. The 14C label is universally distributed among all carbon positions of the phenylalanine portion of the molecule. Briefly, the dipeptide is prepared by reacting the phenylalanine methyl ester hydrochloride salt with trimethylamine‐carboxyborane, triphenylphospine (TPP), CCl4, and triethylamine (TEA) in acetonitrile, for 24 hours. The final product afforded a specific activity of 5.71 mCi/mmol.
Synthesis of 14C‐radiolabeled ractopamine hydrochloride
Authors: Terando Norman H.
Published: October 2006

Ractopamine HCl was uniformly labeled with carbon‐14 in one of two phenyl rings as a requirement for animal metabolism studies. The six‐step synthesis was completed in a 14% yield. Product instability on silica gel complicated purification, but development of a chromatographic method afforded ractopamine ·HCl‐14C with a radiochemical purity of 98.2%.
Synthesis of 14C‐Labelled Cefclidin (E1040)
Authors: Sugiyama Isao , Woolley G. T. , Mizuo Hitoshi , Yamauchi Hiroshi
Published: October 2006

Cefclidin (E1040), a new injectable cephalosporin with potent antipseudomonal activity, was synthesized labelled with carbon‐14, starting from bromo[1‐14C]acetic acid according to the method illustrated in Scheme 1, 2. [14C] Cefclidin, having a specific activity of 3.43 MBq/mg (water content 15.3%, which was based on water content of non labelled compound prepared by the same procedure), was obtained in 2% overall radiochemical yield, with a radiochemical purity of more than 99.1%.
Synthesis of four tritium‐labelled aminowarfarin methyl ketal regioisomers
Authors: Obach R. Scott , Kaminsky Laurence S.
Published: October 2006

6‐Bromo‐4′‐nitro‐, 4′‐bromo‐6‐nitro‐, 4′‐bromo‐7‐nitro‐ and 4′‐bromo‐8‐nitrowarfarin methyl ketals were prepared and together subjected to catalytic tritiation over palladium on charcoal to produce tritium‐labelled aminowarfarin methyl ketals. The four regioisomers were separated by thin‐layer chromatography to yield pure compounds of high (24.9–29.8 Ci/mmol) specific activity.
Synthesis of S‐[3‐(4(5)‐imidazolyl)propyl],N‐[2(4‐{125I}‐iodophenyl)ethyl]isothiourea sulfate (125I‐iodophenpropit), a new probe for histamine H3 receptor binding sites.
Authors: Menge Wiro M. P. B. , Goot Henk Van Der , Timmerman Hendrik , Eersels Jos. L. H. , Herscheid Jacobu S. D. M.
Published: October 2006

The synthesis of the first high specific activity {125I} labelled selective H3 antagonist, Iodophenpropit‐ i.e., S‐[3‐(4(5)‐imidazolyl)propyl],N‐[2‐(4‐{125I}‐iodophenyl)ethyl]isothiourea sulfate is reported.

The radiolabelled compound was prepared by Cu(I)assisted nucleophilic non‐isotopic exchange from the corresponding bromo derivative (VUF 4598). The 125I‐Iodophenpropit was purified using reverse phase HPLC and obtained in a chemical and radiochemical purity >98% and a specific activity of 1900 Ci/mmol.
A Convenient method to synthesize specifically labelled cholesterol with tritium
Authors: Malik Sohail , Kenny Margaret , Ahmad Suhail
Published: October 2006

A simple method is described to label cholesterol with tritium. Cholesterol was first oxidized to 5‐cholesten‐3‐one (2) which was then purified by HPLC. Its structure was established by electron impact (EI) mass spectrometry and 1H‐NMR spectroscopy. The ketone (2) was reduced with NaB3H4 to give specifically labelled cholesterol (C‐33H) at low specific activity.
A convenient method to synthesize N‐[3H]methyl‐N‐nitrosocarbamate transfer reagents
Authors: Mehta Pratibha , Konakahara Takeo , Gold Barry
Published: October 2006

Activated N‐alkyl‐N‐nitrosocarbamates are useful acyl transfer reagents that are employed in the synthesis of N‐alkyl‐N‐nitrosoureas and related N‐nitroso compounds. The nitrosourea products are of chemical and biological interest because they provide access to the in situ generation of highly reactive carbonium type intermediates, which, depending on their structure, can be powerful carcinogens or antineoplastic agents. The availability of radiolabeled nitrosoureas greatly facilitates studies on their chemical and biological activities. Generally, the synthesis of activated nitrosocarbamates requires condensation of radiolabeled alkylisocyanates with the appopriate alcohol. Because radiolabeled alkylisocyanates are not commercially available and/or troublesome to synthesize, we have developed an easy and economical method for preparing N‐[3H]methyl‐N‐nitrosocarbamates suitable for use as transfer reagents utilizing 1,2,2,2‐tetrachloroethyl chloroformate and [3H]methylamine hydrochloride as starting materials.
Synthesis and analysis of the opioid analgesic [14C]‐fentanyl
Authors: Bagley Jerome R. , Wilhelm Jeffrey A.
Published: October 2006

The synthesis of [14C]‐fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [14C]‐Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1‐phenylethyl‐4‐piperidone and [UL‐14C]‐aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [14C]‐fentanyl with the radiolabel in the aniline benzene ring.
A study of irradiation conditions of mercury target with protons to obtain thallium‐201
Authors: Fernandes Lizete , da Silva Constǎncia P. G.
Published: October 2006

The 201T1C1 solution is used in Nuclear Medicine for myocardial visualization. 201T1 is a cyclotron‐produced radioisotope, obtained indirectly from the decay of 201Pb or directly by irradiating mercury with protons. In this work, 201T1 was obtained by irradiating a natural mercury target with protons in the energy range of 24 to 19 MeV, using the IPEN's CV‐28 cyclotron. Range calculations of protons in the targets and in the materials used to degrade the proton beam energy were made. At the end of the bombardment of a 329 μm thickness (6 MeV thickness) target of natural metallic mercury with 19 MeV protons provided a yield of 10 MBq 201T1/μA.h.
Microbiological preparation of D‐[3,4‐13C2]glucose
Authors: Baxter Robert L. , Baxter Helen C. , McGregor Christopher J.
Published: October 2006

A simple and effective synthesis of D‐[3,4‐13C2]Glucose (60 atom % 13C2) via 13C enriched α,α' trehalose (1) produced from sodium [1‐13C]acetate by sporulating yeast is described.
Synthesis of Hexadecylphospho[methyl‐14C]‐choline
Authors: Geilen C. C. , Samson A. , Wieder Th. , Wild H. , Reutter W.
Published: October 2006

Hexadecylphospho[methyl‐14C]‐choline was synthesized in two steps from the tetra‐n‐butyl‐ammonium salt of phosphoryl[methyl‐14C]‐choline and 1‐bromohexadecane, and purified by column chromatography on silica gel. The total yield of the radioactive synthesis was 35%, whereas the total yield of the non‐radioactive synthesis was 40%. Hexadecylphospho[methyl‐14C]‐choline may serve as a useful tool for pharmacokinetic and biochemical studies of this new antitumor drug.
An elegant synthesis of [1‐14C] hexadecyltrimethylammonium bromide [CTAB]
Authors: Gurudutt K. N. , Srinivas P. , Srinivas S.
Published: October 2006

Hexadecyltrimethylammonium bromide, a cationic detergent having a wide range of applications, was synthesised from [1‐14C] hexadecanoic acid via its methyl ester, alcohol and bromide, in an overall yield of 84%. It had a specific activity of 6.30 uCi/mmol and a radiochemical purity of 97.6%.
Synthesis of carbon‐14 labeled vigabatrin
Authors: Schuster Albert J. , Wagner Eugene R.
Published: October 2006

Carbon‐14 labeled vigabatrin was synthesized in 5 steps from 5‐hydroxymethyl‐2‐pyrrolidone tosylate and NaCN‐[14C]. A key step involved reduction of the resulting nitrile in the presence of excess dimethylamine to give the dimethylamino‐ethyl 2‐pyrrolidone derivative in one step. This afforded an overall radiochemical yield of 22% and radiochemical purity greater than 98%.
Carbon‐11 labelling of an inhibitor of acetylcholinesterase: [11C]physostigmine
Authors: Bonnot‐Lours S. , Crouzel C. , Prenant C. , Hinnen F.
Published: October 2006

Physostigmine, an alkaloid from calabar bean is a strong inhibitor of acetylcholinesterase (Ki=3.33 ± 0.26 × 10−6M) and has been used clinically in the treatment of glaucoma, atropine intoxication, myasthenia gravis and more recently, in experimental trials in Alzheimer's disease. In order to study the AChE activity in the brain by positron emission tomography, we have undertaken the labelling of physostigmine with carbon‐11. The synthesis involves the reaction of [11C]methylisocyanate with eseroline. [11C]Methylisocyanate was obtained by heating [11C]acetylchloride with tetrabutylammonium azide in toluene. The synthesis of [11C]CH3COCl involves the carbonation of methylmagnesium bromide in THF with cyclotron produced [11C]carbon dioxide and the addition of phthaloyl dichloride. The [11C]methylisocyanate is distilled into a solution of eseroline in ether with a small piece of sodium. After 10 minutes at 25°C, the solution is purified by HPLC and the appropriate fraction collected.

Starting with 55.5 GBq (1.5 Ci) of [11C]carbon dioxide, 0.92‐1.48 GBq (25‐40 mCi) of [11C]Physostigmine are obtained 57 minutes after EOB.
Synthesis of a novel 123I‐labelled derivative of GBR12783, a potential agent for SPECT imaging of dopamine‐reuptake sites
Authors: He Xiao‐Shu , Lee Kan Sam , Weinberger Daniel , de Costa Brian R.
Published: October 2006

[123I]1‐[2‐(Diphenylmethoxy)ethyl]‐4‐[3‐(m‐iodophenyl)‐2‐propenyl]piperazine ([123I]2), a potential SPECT imaging agent for dopamine reuptake sites was efficiently synthesized in 4 steps from 1‐[2‐(diphenylmethoxy)ethyl]piperazine (3). A key step in the synthesis was the selective AIH3‐mediated reduction of 1[2‐(diphenylmethoxy)ethyl‐4‐(m‐bromocinnamoyl] piperazine (4) to 1‐[2‐(diphenylmethoxy)ethyl‐4‐(3‐(m‐bromophenyl)‐2‐propenyl]piperazine(5). The 123I label of [123I]2 was introduced in the final step in up to 90% radiochemical yield by treatment of the organotin precursor 1‐(2‐(diphenylmethoxy)ethyl‐4‐[3‐[(m‐(tributyl stannyl)phenyl]‐2‐propenyl]piperazine (6) with Na123I in aqueous CH3CO3H.
A convenient method for the synthesis of radioactively labelled aryl glycosides
Authors: Griffin Simon D. J. , Donaldson Iain A.
Published: October 2006

Fluoride‐directed methylation of the aryl hydroxyl of hydroxyphenyl glycosides with radioactive methyl iodide allows the incorporation of label under mild conditions that preserve the glycosidic link. The effectiveness of this approach has been demonstrated by the synthesis of two 14C‐labelled aryl α‐glycosides.
A comparison of the incorporation of 123I and 18F into 1‐[1‐(3‐hydroxyphenyl) cyclohexyl]‐4‐(methanesulfonyloxy)piperidine by nucleophilic displacement with 123I− and 18F−
Authors: He Xiao‐Shu , Kiesewetter Dale O. , Lee Kan Sam , Mattson Mariena V. , Weinberger D. R. , de Costa Brian R.
Published: October 2006

Unlabelled and labelled 4‐fluoro‐ and 4‐iodo‐1‐[1‐(3‐hydroxyphenyl)cyclohexyl]piperidines (3 and 4, respectively), derivatives of phencyclidine, were synthesized in 3‐steps via nucleophilic displacement reaction of 1‐[1‐(3‐hydroxyphenyl) cyclohexyl]‐4‐(methanesulfonyloxy)piperidine (8). The displacement reaction with 3 molar equivalents of Bu4N+I− gave 58% of 4 with no detectable methanesulfonate elimination. Reaction of a large excess of 8 with Na123I− under similar conditions gave up to 40% yield of [123I]8. In contrast reaction of 8 with 3 molar equivalents of unlabelled Bu4N+F− in refluxing acetonitrile yielded only 3.1% of 3 and 97% of elimination product. Similarly, reaction of a large excess of 8 with Bu4N+18F− at 80 °C in acetonitrile failed to yield detectable quantities of [18F]3. However, low (0‐4%) yields of [18F]3 were obtained using 18F− in the presence of varying proportions of inorganic base and Krytofix in acetonitrile.
A one‐pot synthesis of (±)‐(ring 13C6)‐mandelic acid
Authors: Sirimanne Sarath R. , Patterson Donald G.
Published: October 2006

A one‐pot synthesis of (±)‐(ring 13C6)‐mandelic acid is reported. [Ring 13C6]‐benzaldehyde was cyanosilylated with trimethylsilyl cyanide (TMSCN)/Znl2. The resulting cyanosilylated adduct was hydrolyzed with concentrated hydrochloric acid without purification. The workup involves evaporation to dryness and extraction of the (±)‐(ring 13C6)‐mandelic acid with hot benzene. After one crystallization, the synthesis produced an overall yield of 65% of (±)‐(ring 13C6)‐mandelic acid that was about 98% pure by HPLC with UV detection.
Racemic synthesis and enantiomeric conversion of [1‐13C] valine
Authors: Polach Kevin J. , Shah Sapan A. , Laiuppa John C. , Lemaster David M.
Published: October 2006

A Strecker synthesis of isobutyraldehyde, K13CN and ammonia produced D,L‐[1‐13C] valine in 83% yield. This racemic mixtue was then converted to the L‐form via a D‐amino acid oxidase ‐ branched amino acid aminotransferase system in an overall yield of 75% based on K13CN. Given the generality of the Strecker synthesis as well as the broad substrate specificity of the oxidase and aminotransferase enzymes, it is anticipated that this procedure will be comparably efficient for most standard aliphatic and aromatic amino acids.
The preparation of tritium labelled biocompatible polymers
Authors: Russell Jeremy C. , Jones John R. , Vick Terrence A. , Stratford Peter W.
Published: October 2006

The preparation of tritiated phosphoryl choline containing linear polymers by the reduction of an acetylenically unsaturated polymer with tritium gas is described. Homogeneous catalysis was used and the product was analysed by 1H and 3H‐nmr spectroscopy. The use of lanthanide shift reagents showed that 98% of the isotope was located in the 7 and 8 positions of the hydrophobic chains.
Synthesis of 11‐[3H]‐arteether, an experimental antimalarial drug
Authors: Pu Yu‐Ming , Ziffer Herman
Published: October 2006

The triphenylphosphine hydrobromide‐catalyzed addition of a proton from ethanol to anhydrodihydroartemisinin (5) has been employed for the synthesis of 2 and 4 Use of 1.5 equivalents of EtO2H or EtO3H yielded 11‐[3H]‐β‐arteether as the major product.
Synthesis of the enantiomers and three racemic metabolites of carvedilol labeled to high specific activity with tritium
Authors: Senderoff S. G. , Villani A. J. , Landvatter S. W. , Garnes K. T. , Heys J. R.
Published: October 2006

Carvedilol (SK&F 105517) possesses unique cardiovascular activity, and is under development for indications such as angina and hypertension. Tritium labeled enantiomers of Carvedilol and racemates of three metabolites were needed for pharmacologic and drug metabolic studies. These compounds were synthesized by catalytic tritium‐halogen exchange using tritium gas and 10% palladium‐on‐carbon catalyst. The precursors were polyhalogenated in the carbazole ring. Direct electrophilic bromination of the enantiomers of Carvedilol gave precursors that were converted to the corresponding tritiated final products by catalytic tritium halogen exchange. Bromination of 4‐(2,3‐epoxypropyloxy)‐9H‐carbazole gave an intermediate that was converted to the halogenated precursors of the racemic metabolites. Elaboration of this intermediate, 1,3,6‐tribromo‐4‐(2,3‐epoxypropyloxy)‐9H‐carbazole, to the desired metabolite precursors was achieved by nucleophilic epoxide opening with suitably functionalized N‐benzyl aryloxyethylamines. Catalytic tritium‐halogen exchange upon the brominated metabolite precursors was accompanied by cleavage of N‐ and Q‐benzyl protecting groups. Radiochemical purities of all tritiated final products were greater than 98% after preparative HPLC. Specific activities of the final products, determined by mass spectrometry, ranged from 35 to 76 Ci/mmol. Optical purity of the Carvedilol enantiomers, determined by chiral HPLC, was greater than 99%
A facile synthesis of sodium 3‐[1‐14C]‐ethyl‐7‐isopropyl‐1‐azulenesulfonate
Authors: Shimada Takeshi , Yanagisawa Takashi , Tomiyama Tsuyoshi , Okazaki Mitsuo
Published: October 2006

Sodium 3‐ethyl‐7‐isopropyl‐1‐azulenesulfonate1, a new therapeutic agent for stomatitis, pharyngitis and ophthalmia was labelled with carbon‐14 in the ethyl group attached to the azulene ring for use in metabolic studies.14C‐labelled1with a specific activity of 1.98 GBq/mmol was prepared in four steps in 39.3% overall chemical yield from [1 ‐14C]acetic acid sodium salt.
Synthesis of [32P]labelled 1‐O‐alkyl‐2‐desoxy‐2‐amino‐sn′‐glycero‐3‐phosphocholines
Authors: Deigner H. P. , Fyrnys B.
Published: October 2006

The syntheses of N‐substituted 1‐O‐alkyl‐2‐desoxy‐2‐amino‐sn‐glycero‐3‐[32P]phosphocholines were performed in four steps starting from [32P] POCl3 and the corresponding 1‐O‐alkyl‐2‐amino‐propane‐3‐ols in 5‐7% total yield.
Synthesis of [methyl‐14C]‐N‐methylputrescine
Authors: Secor H. V. , Izac R. R. , Hassam S. B. , Frisch A. F.
Published: October 2006

[Methyl‐14C]‐N‐methylputrescine was prepared from [14C]methylamine hydrochloride in five steps. Reaction of benzaldehyde and [14C]methylamine (10 mCi) followed by catalytic hydrogenation yielded [methyl‐14C]‐N‐methylbenzylamine. The key step in this process is the alkylation of [methyl‐14C]‐N‐methylbenzylamine in aqueous medium with 4‐bromobutyronitrile. The radiochemical purity of the final product after two successive catalytic hydrogenations was in excess of 97%. The radiochemical yields in two successive runs were 26 and 38%, based on starting [14C]methylamine, with specific activities of 22 and 23 mCi/mmol, respectively. This sequence provides a convenient and efficient regioselective radiosynthesis of [methyl‐14C]‐N‐methylputrescine.
Preparation of 14C‐labelled dimethylsilane‐1,1‐diol
Authors: Cella J. A. , Carpenter J. C.
Published: October 2006

The preparation of 14C‐labelled dimethylsilane‐1, 1‐diol in two steps from 14C‐labelled diphenyldimethylsilane is described. Aluminum chloride catalyzed protodesilylation of diphenyldimethylsilane with HCl in dichloromethane or dimethyldichlorosilane at 0–5°C affords labelled dimethyldichlorosilane which is hydrolyzed in the presence of triethylamine to afford the title compound in 45–60% yield.
Synthesis of a [13CO2H]‐labelled bilirubin
Authors: Nogales Daniel F. , Lightner David A.
Published: October 2006

Bis‐[13CO2H]‐mesobilirubin‐XIIIα was synthesized in 11% overall yield in 10 steps from 99% enriched K13CN. The synthetic methods are adapted to a scale of a few grams to a few milligrams.
Synthesis of isotopically labelled WIN 33377, an anticancer agent related to hycanthone
Authors: Duffin Gordon R. , Ellames George J. , Smith David I. , Wedge Karen J.
Published: October 2006

14C labelled and 13C,15N labelled WIN 33377,1, 1‐(2‐diethylaminoethylamino)‐4‐(methanesulphonamidomethyl)thioxanthen‐9‐one, have been prepared by related routes using the known 1‐(2‐diethyl‐aminoethylamino)thioxanthen‐9‐one, 4, as starting material and introducing the label with cyanide prior to further elaboration.
A novel one step approach to small scale labeling of organic compounds with hydrogen isotopes
Authors: Malik Sohail , Kenny Margaret , Doss George , John Varghese
Published: October 2006

A rapid method to generate tritium gas for small scale labeling is described. Tritium labelled sodium borohydride is used with cobalt (II) chloride to generate isotopic hydrogen gas. The reaction was carried out in a closed vessel and three different compounds were concurrently labelled. This simple and inexpensive method can be applied to a broad range of molecules and does not require any special set up.
Complexation behaviour of tin(II) ion with derivative of p‐aminohippuric acid
Authors: Djurdjevic Predrag , Maksin Tatjana , Veselinovic Dragan
Published: October 2006

Complex formation between tin(II) ion and p‐(biscarboxymethyl)‐aminomethyl‐carbamino‐hippuric acid (PAHIDA) in 0.5 M NaClO4 ionic medium at 298 K, was studied by means of u.v. spectrophotometry and glass electrode potentiometric titrations. In the concentration range 0.09 ⩽ [Sn] ⩽ 0.150, 0.5 ⩽ [PAHIDA] ⩽ 3.0 (mmol dm−3) and 1.30 ⩽ pH ⩽ 6.5, mathematical analysis of potentiometric data, with the aid of general least‐squares programme Superquad, indicates the formation of the following complexes and their respective stability constants (log (β ± σ)): [Sn(H2PAHIDA)] (12.98 ± 0.15), [Sn(HPAHIDA)] (9.38 ± 0.05), [Sn(PAHIDA)] (5.74 ± 0.01) and [Sn(OH)PAHIDA] (1.55 ± 0.09) as well as several pure hydrolytic complexes of tin(II).

The effect of tin(II)‐PAHIDA complexation on labelling yield of PAHIDA with 99mTcO4− was investigated. The optimum yield (90%) was achieved at PAHIDA to tin(II) concentration ratio 30:1 and pH = 5.5.
Synthesis of a new selective borotritide : [3H]lithium9‐boratabicyclo[3.3.1]nonane. Some applications to the preparation of secondary and primary [3H] alcohols
Authors: Rasset Christine , Rousseau Bernard
Published: October 2006

[3H]lithium 9‐boratabicyclo[3.3.1]nonane, at specific activity of 52–55 Ci/mmol, was synthesized by reduction of B‐OMe‐9‐BBN with lithium tritide. Its reducing characteristics were illustrated by the synthesis of [17‐3H] estradiol, [2‐3H] dihydrotetrabenazine and 1‐(hydroxy[3H]methyl)naphtalene, with good radiochemical yields and high specific activities.
Synthesis of mutagenic 2,4‐dinitro‐[7‐14C]benzaldehyde
Authors: Shoji Miki , Mori Masa‐Aki , Sayama Michio , Kozuka Hiroshi , Honda Takashi
Published: October 2006

2,4‐Dinitro‐[7‐14C]benzaldehyde (4), a mutagenic substance which may have an unique metabolic activating pathways, was synthesized as a tracer for the detection of adducts of 4 with macromolecules. The preparation was performed in four steps from [7‐14C]toluene to give an overall radiochemical yield of 20% after purifying by TLC. The radiochemical purity was over 98%.
Isolation and preparation of 3H‐tetrandrine
Authors: Huang Xun Yang , Wang Yin , De Lu Zang
Published: October 2006

Tetrandrine is a bisbenzytehahydroisoquinoline alkaloid. Its structure is very complex and the preparation of labeled derivatives is difficult. We have prepared 3H‐tetrandrine using the tritium gas exposure method.1 This method produces many fragments which make isolation and purification of small quantities difficult. We investigated these fragments of unlabeled d‐tetrandrine and found almost all contain one to several hydroxide groups. Using this information, we designed a two‐step paper chromatography method for isolation and purification of 3H‐Tetrandrine. This method involves the application of a pH 4.7 Na2HPO4‐citric acid buffer to the paper to block the migration of hydroxide group fragments of tetrandrine. 3H‐tetrandrine was successfully with a radiochemical purity of 90%.
Synthesis of the racemate and individual enantiomers of [11C]methylphenidate for studying presynaptic dopaminergic neuron with positron emission tomography
Authors: Ding Y.‐S. , Sugano Y. , Fowler J. S. , Salata C.
Published: October 2006

Carbon‐11 labeled dl‐threo‐methylphenidate (methyl‐2‐phenyl‐2‐(2‐piperidyl)acetate, Ritalin), a psychostimulant drug widely used to treat attention deficit hyperactivity disorder, was prepared in two steps: O‐methylation of the N‐protected dl‐threo‐ritalinic acid derivative with [11C]methyl iodide followed by deprotection. The same strategy was applied for the preparation of C‐11 labeled individual enantiomers of threo‐methylphenidate from N‐protected d‐threo‐ or l‐threo‐ritalinic acid. The subsequent C 18 sep‐pak and reverse‐phase HPLC purification resulted in ca. 40% radiochemical yield with a total synthesis time of 40 minutes and an average specific activity of 1.5 Ci/μmole (at EOB).
The radiosynthesis of a new potential glucose transport protein tracer: 3‐[125I]iodophloretin
Authors: Mertens J. , Terriere D. , Boumon R.
Published: October 2006

Phloretin (2′,4′,6′‐trihydroxy‐3‐(4‐hydroxyphenyl)‐propiophenone) is a glucose transport (GLUT) blocker acting at the extracellular part of the GLUT protein. Labelling this compound with radioiodine can provide a tracer for elucidating in vitro and in vivo the role of GLUT's in cells showing an increased glucose metabolism. As the inhibition of GLUT by phloretin is supposed to occur at the 2′,4′,6′‐trihydroxyphenyl site, the radioiodine is substituted on the 3‐position of the 4‐hydroxyphenyl group. Direct electrophilic substitution on this position is not possible due to highly activated sites in the trihydroxyphenyl group. 3‐Bromophloretin, the precursor for radioiodination, is prepared using a new method, a saturation substitution followed by the elimination of the unstable bromine atoms. Radioiodinated phloretin is obtained with a labelling yield of 75% by applying Cu+1‐assisted radioiodo for bromo exchange at 140°C. Pure non carrier added tracer results from HPLC separation coupled to a mini‐column preconcentration and recovery (± 70% overall yield).
Investigations on the chemistry of berbanes 15(1) synthesis of the allo‐berbane skeleton labelled with 14C
Authors: Szammer János , Dörnyei Gábor , Szántay Csaba
Published: October 2006

[14‐14C]‐allo‐berbane‐14‐ol: (7,8‐methylenedioxy‐14α‐hydroxy‐[14‐14C]‐allo‐berbane, [14‐14C]1 spec, act.: 405 MBq/mM) was synthesized in nine reaction steps from K14CN (overall radioactive yield: 2.8%).
New processes for the synthesis of 2,6‐dichloro‐3‐methylaniline‐Ph‐UL‐14C and methyl 6‐chloroanthranilate‐Ph‐UL‐14C
Authors: McKendry L. H. , Stanga M. A.
Published: October 2006

Two new processes were developed for the synthesis of 2,6‐dichloro‐3‐methylaniline‐Ph‐UL‐14C (1), a key intermediate in the synthesis of a Dow Elanco experimental product presently being considered for commercialization. Both processes afford product in much higher yields than that previously reported in the literature. One of the processes was subsequently applied to the synthesis of methyl 6‐chloroanthranilate‐Ph‐UL‐14C (12), used as an intermediate for a second potential product.
The radiosynthesis of No‐carrier added [1‐11C]allyl alcohol evidence for the formation of a new reducing species: Lithium aluminium hydride — vinylmagnesium bromide
Authors: Lasne Marie‐Claire , Moreau Bernard , Cairon Philippe , Barré Louisa
Published: October 2006

Lithium aluminium hydride in the presence of vinylmagnesium bromide (1:1 molar ratio) affords a potent reagent for the reduction of acrylic acid to allyl alcohol (ratio of allyl alcohol to 1‐propanol: 3:2). This reducing mixture has allowed the preparation of nocarrier added [1‐11C]allyl alcohol with a 25% yield (decay corrected at the end of radionuclide production, overall synthesis time including GC: 40 min) in a one step procedure from [11C]carbon dioxide (C‐11: t1/2:20.4 min). [1‐11C] 1‐propanol was obtained in parallel with a 6.5% yield.