bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of (S)‐1‐[3‐hydroxy‐2‐(phosphonylmethoxy) propyl]‐[2‐14C]cytosine ((S)‐[14C] HPMPC)
Authors: Haynes U. J. , Swigor J. E. , Bronson J. J.
Published: October 2006

The synthesis of (S)‐[14C]HPMPC (4) is described. Heating [2‐14C]cytosine (1) in N, N‐dimethylformamide with (R)‐3‐0‐benzyl‐2‐0‐[(diethylphosphonyl)methyl]‐1‐0‐(methylsulfonyl) glycerol in the presence of cesium carbonate gave (S)‐1‐[3‐benzyloxy‐2‐(diethylphosphonylmethoxy) propyl]‐[2‐14C]cytosine (2). Reduction with palladium hydroxide on carbon in cyclohexene yielded (S)‐1‐[3‐hydroxy‐2‐(diethylphosphonylmethoxy)propyl]‐[2‐14C] cytosine (3). Deprotection of the diethylphosphonate ester with bromotrimethylsilane and treatment with water produced 190 mg of [14C] HPMPC (4) having a specific activity of 21.2 μCi/mg and a radiochemical purity 98.5% in an overall yield of 5.6%.
Stereoselective synthesis of stable isotope‐labeled L‐α‐amino acids: Chemomicrobiological synthesis of 13C‐ and 2H‐labeled L‐cysteine
Authors: Unkefer Clifford J. , Hanners John L. , Ehler Deborah S.
Published: October 2006

Tryptophan synthase catalyzes the nucleophilic replacement of the hydroxyl group at C‐3 of L‐serine. This enzyme can use benzyl mercaptan as a nucleophile in the conversion of serine to S‐benzyl‐L‐cysteine which is deblocked by treatment with sodium in liquid ammonia to yield L‐cysteine. A strain of E. coli engineered to overproduce tryptophan synthase was used in the conversion of L‐serine to L‐cysteine. Labeled serine was prepared biosynthetically as described previously.
[2‐14C] 5‐fluorouracil metabolism to [14CO2]
Authors: Rabinowitz Joseph L.
Published: October 2006

The rate of 14CO2 production from 2‐14C‐5‐FU was measured in rats bearing the Novikoff ascites hepatoma. Tracer amounts were injected and 14CO2 collected over a 6‐hour period. As the tumor cells proliferated the rate of 2‐14C‐5‐FU oxidation decreased markedly over the approximately 12± 2 days between implantation of tumor cells and death. On the day of innoculation of tumor cells, oxidation proceeded nearly linearly until almost 50% of the injected 2‐14C‐5‐FU was converted to 14CO2 in about 4 hours. With time after tumor innoculation, the rate of 14CO2 collection declined; ten days after innoculation only about 27% was oxidized by 4 hours, and at the terminal stage it declined to about 18% over 4 hours. Calculated from the time curves, the time oxidation of 25% of the injected trace dose increased from 88± 27 min to 195± 42 min after ten days, to 300 ± 59 min at the moribund state after 12 ± 2 days.

Similar decreases in oxidation rate of 5‐FU were observed during growth of a solid implanted mammary carcinoma and for two other 2‐14C‐labelled pyrimidines, uracil and thymine injected in trace quantities.

By comparing cancer subjects with themselves at different time‐intervals from the onset of the disease and treatment, it might be possible to guage treatment dosages in the progress of the disease.
Synthesis of (6R,7R)‐7‐[2‐(5‐aminio‐1,2,4‐[5‐14C]thiadiazol‐3‐yl)‐(Z)‐2‐methoxyimiyiminoacetamido]‐3‐[(4‐carbamoyl‐1‐quinuclidinio)methyl]ceph‐3‐em‐4‐carboxylate([14C]E1040)
Authors: Sugiyama Isao , Nomoto Seiichirou , Mizuo Hitoshi , Yamauchi Hiroshi
Published: October 2006

(6R,7R)‐7‐[2‐(5‐amino‐1,2,4‐thiadiazol‐3‐yl)‐(Z)‐2‐methoxyiminoacetamido]‐3‐[4‐(carbamoyl‐1‐quinuclidinio)methyl]ceph‐3‐em‐4‐carboxylate (E1040), a new injectable cephalosporin with potent antipseudomonal activity, was synthesized labelled with carbon‐14, starting from potassium [14C]thiocyanate with 2‐(N‐chloroamidino)‐2‐(methoxyimino)acetic acid (I) gave (5‐amino‐1,2,4‐[5‐14C]thiadiazol‐3‐yl‐2‐methoxyimino)acetic acid (II). 7‐Amino‐3‐[(4‐carbamoyl‐1‐quinuclidinio)methyl]ceph‐3‐em‐4‐carboxylate hydrochloride (IV) was acylated with the above acid chloride using the PCl5 method, to afford the title compound (V); [14C]E1040, having a specific activity of 3.74 MBq/mg (as its anhydride), was obtaind in 47% overall radiochemical yield, with a radiochemical purity of more than 98.1%.
Synthesis of 4‐ and 10‐deuterated neryl and geranyl‐β‐D‐glucosides and their use in corroboration of a mechanism proposed for the fragmentation of heterosides in tandem mass spectrometry
Authors: Salles Christian , Jallageas Jean‐Claude , Beziat Yves , Cristau Henri‐Jean
Published: October 2006

In order to corroborate a mechanisms proposed for the fragmentation of the molecular ion of heterosides, involving a hydride migration from the aglycome to the osidic unit, the 4‐[2H2]‐10‐[2H3]‐labelled neryl and geranyl‐β‐D‐glucosides 9 and 10 have been synthesised.

Deuterated ketone 1 was prepared in >99% isotopic abundance by base catalysed exchange with [2H2]‐water, and was reacted under Wittig‐Horner conditions furnishing the corresponding α, β‐unsaturated esters 3 and 4.

Selective reduction of the ester group can be performed with DIBAl‐H, whereas LiAlH4 give a secondary reduction of the CC double bond.

The published procedure (13) for the β‐D‐glucosidation of alochols has been modified in order to optimise conditions on the deuterated nerol and geraniol.

By comparison of collision spectra (NICI/CAD) of pure deuterated and undeuterated neryl and geranyl‐β‐D‐glucosides the proposed fragmentation mechanism is fully corroborated.
Preparation and evaluation of cationic 99Tc/99mTc dimethoxy‐ and diethoxy‐hexanedione dioxime complexes
Authors: Su Z. F. , Linse K. H. , Steinmetz H. J. , Schwochau K.
Published: October 2006

The new ligands 1,6‐dimethoxy‐3,4‐hexanedione dioxime (DMHD) and 1,6‐diethoxy‐3,4‐hexanedione dioxime (DEHD) were synthesized and their boron containing 99Tc/99mTc complexes, formed by reduction of pertechnetate with BH4‐, were isolated, purified and characterized by IR/UV/VIS spectroscopy and FAB mass spectrometry. These rather stable cationic complexes differ significantly in lipophilicity as assessed by their octanol/saline partition coefficients and HPLC capacity factors. Unexpectedly the organ uptake and clearance of both complexes in mice proved to be very similar with only the uptake of 99mTc‐DMHD in the kidneys being enhanced.
Synthesis of deuterated polyethylene glycols
Authors: Schnabel Ruth
Published: October 2006

The synthesis of polyethylene glycols [α‐Hydro‐ω‐hydroxypoly(oxy‐1, 2‐ethanediyl)‐dx], deuterated in the chain, up to the lenght of the chain of 20 carbons was achieved by reaction of ethylene glycol‐d, with iodine as catalysts.
The preparation of 14C‐labeled FK‐506
Authors: O'connor Stephen P. , Ellsworth Robert L. , Omstead Mary Nallin , Jenkins Rosalind G. , Kaplan Louis
Published: October 2006

Utilizing sodium [1−14C]propionate as a precursor, [14C]FK‐506, labeled at carbon atoms 10, 16, 18, 21a, 24, and 26, was produced by fermentative biosynthesis. Extractive isolation followed by chromatographic purification provided material of purity suitable for metabolism studies.
An efficient synthesis of S‐γ‐[(4‐trifluoromethyl)‐phenoxy]benzenepropanamine‐[1‐14C] maleate, an important metabolite of fluoxetine hydrochloride
Authors: Wheeler William J.
Published: October 2006

S‐γ‐[(4‐Trifluoromethyl)phenoxy]benzenepropanamine‐[1‐14C] maleate has been prepared in six steps from R‐(‐)1‐phenyl‐1,2‐ethanediol. The isotope was incorporated by the reaction of NaCN‐[14C] with the tert. butyldimethylsilyl ether of R‐(‐)1‐phenyl‐1,2‐ethane‐diol 2‐tosylate. Borane reduction and arylation, followed by salt formation yielded S‐γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[1‐14C] maleate.
Synthesis of tritiated derivatives of the diphenylether herbicides acifluorfen and acifluorfen methyl
Authors: Mornet René , Gouin Lucien , Matringe Michel , Scalla René , Swithenbank Colin
Published: October 2006

Acifluorfen 1 and acifluorfen methyl 2, two herbicides of the diphenylether family, are inhibitors of protoporphyrinogen oxidases. Two tritiated derivatives of these compounds, namely 3‐[3H]‐5‐[2‐chloro‐4‐(trifluoromethyl)phenoxy]‐2‐nitrobenzoic acid [3H]‐1, and methyl 3‐[3H]‐5‐[2‐chloro‐4‐(trifluoromethyl)phenoxy]‐2‐nitrobenzoic acid [3H]‐2, have been synthesised from 3‐[3H]‐5‐hydroxybenzoic acid, in order to probe their interactions with the target enzymes.
Synthetic strategies in the preparation of regiospecifically chlorine‐37 labeled polychlorinated dibenzo‐p‐dioxins
Authors: Mahiou Belaid , Deinzer Max L.
Published: October 2006

A series of thirteen regiospecifically chlorine‐37 labeled polychlorodibenzo‐p‐dioxins were synthesized via the Sandmeyer reaction. Nitrochlorodibenzodioxins which were obtained by a base promoted condensation of catechols and dinitropolyhalobenzenes were reduced and converted to the diazonium salts. Chlorine‐37 was introduced using cuprous chloride‐37. The isotopic enrichment was in the range 75‐96%.
A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer
Authors: Wheeler William J. , O'bannon Douglas D.
Published: October 2006

The 14C‐isotopomer of dapoxetine‐[14C] HCl (S (+)‐N,N‐dimethyl‐α‐[2‐(1‐naphthalenyloxy)ethyl‐2‐14C]benzenemethanamine hydrochloride, 1a), a potent serotonin re‐uptake inhibitor has been prepared by a chiral synthesis, starting with tert.‐butyloxyphenylglycine (3). Borane reduction, followed by activation of the resulting alcohol 4 as its mesylate 5b, provided the chiral starting material. The radiolabel was introduced by reaction of 5b with sodium cyanide‐[14C]. The desired product (1) was then elaborated from nitrile 6a,b via a five step synthesis in an overall 19.5% radiochemical yield.
A microscale synthesis of a promising radiolabelled antitumor drug: Cis‐1,1‐cyclobutanedicarboxylato (2R)‐2‐methyl‐1,4‐butanediamine platinum(II), NK121
Authors: Suwa Masato , Kogawa Osamu , Nowatari Hiroyoshi , Murase Yuko , Homma Yoshio , Hashimoto Yutaka
Published: October 2006

A promising antitumor drug, cis‐1,1‐cyclobutane‐dicarboxylato (2R)‐2‐methyl‐1,4‐butanediamine platinum(II), NK121, was synthesized from radionuclides of platinum such as 193mPt, 195mPt and 191Pt which were produced by neutron irradiation of enriched 192Pt. The overall yield was 38.6% in a synthesis time of 10 hours. The radioactivities present in 8.39 mg of NK121 were 115.3 μCi as 193mPt, 29.9 μCi as 197Pt, 22.0 μCi as 195mPt, and 4.8 μCi as 191Pt at the end of synthesis. The specific activity of the NK121 was 13.7 μCi (193mPt)/mg NK121 at the end of synthesis. The radiochemical purity of NK121 was typically 99 %. HPLC analyses confirmed that NK121 was in an adequate chemical purity and suitable for animal experimentation.
Preparation of 14C‐ and 18O‐enriched allyl alcohol (propanol free)
Authors: Kupczyk‐Subotkowska Lidai , Shine Henry J.
Published: October 2006

Preparations of specifically labeled [1‐14C]‐, [3‐14C]‐ and [1‐18O]allyl alcohol are described. The syntheses were achieved, respectively, in 7, 11 and 9 steps, with overall yields of 33%, 10% and 38%.

Commercially available K14CN, CH314COONa and H218O were used as the starting materials.
Production and purification of mixed 14C‐labelled peptides derived from plant biomass
Authors: Ling John R. , Bronwen Cooper P. , Parker Stephen J. , Armstead Ian P.
Published: October 2006

Procedures are described for the production and purification of 14C‐labelled peptides of mixed composition, derived from phytomass. Barley seeds (Hordeum vulgare) were germinated and grown in the dark for 6 days. On day 7, the seedlings were exposed to light in a 14CO2 atmosphere for 24 h. The plant leaves were harvested and their water‐soluble 14C‐labelled proteins extracted. These 14C‐proteins were partially digested by sequential incubation with pepsin, α‐chymotrypsin and trypsin. The resulting 14C‐labelled peptides were separated from contaminating amino acids by elution from columns of copper‐Chelex resin, and finally fractionated by gel‐filtration chromatography and assigned to groups according to molecular size. The purified 14C‐peptides ranged in relative molecular mass up to approximately 5,000, possessed a purity in excess of 97%, and were radiolabelled in all amino acid residues with an average specific radioactivity of 450 Bq/μmol. The methods described can be readily adapted to produce not only mixed 14C‐labelled peptides of any required attribute, such as molecular size or ionic charge, but also mixed 14C‐proteins of 14C‐amino acids.
14C‐labeling of a novel anxiolytic agent tandospirone
Authors: Nishioka Kazuhiko , Kanamaru Hiroshi
Published: October 2006

N‐[4‐[4‐(2‐Pyrimidinyl)‐1‐piperazinyl]butyl]bicyclo‐[2.2.1]heptane‐2,3‐di‐exo‐carboxyimide dihydrogen citrate (tandospirone), a novel anxiolytic agent, was labeled with carbon‐14 individually at the imido carbonyl group and the pyrimidinyl ring. The synthesis of carbonyl‐labeled tandospirone was achieved according to the scheme shown in Fig. 3. Diels‐Alder reaction of maleic anhydride (2) with cyclopentadiene (3) afforded the endo anhydride (4), which was transformed into the imide (5) by treating with ammonia water. Thermal isomerization of the endo imide (5) and subsequent chromatographic separation gave the pure exo compound (6). Catalytic hydrogenation of 6 followed by alkylation with 1,4‐dibromobutane (8) yielded the bromide (9a). Condensation of 9a with N‐(2‐pyrimidinyl)piperazine (10a) followed by treatment of the resulting disubstituted piperazine (11a) with citric acid afforded [carbonyl‐14C]tandospirone (1a). The overall yield of 1a was 22% from 2.

The similar method was applied to the synthesis of pyrimidinyl‐labeled tandospirone as shown in Fig. 4. Condensation of 2‐chloro[2‐14C]pyrimidine (12) with anhydrous piperazine gave the pyrimidinylpiperazine (10b). N‐alkylation of 10b followed by treatment with citric acid afforded [pyrimidinyl‐2‐14C]tandospirone (1b). The overall yield of 1b was 68% from 12.
An enantioselective synthesis of S‐γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐14C] hydrochloride, an important metabolite of fluoxetine hydrochloride
Authors: Wheeler William J.
Published: October 2006

The S‐enantiomer of γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐14C] hydrochloride has been prepared in eight steps from acetophenone‐[carbonyl‐14C]. The key step in the synthesis involved the enantioselective reduction of R‐2‐chloroacetophenone‐[1‐14C] with (‐)‐diisopinocampheylchloroborane in an 86.5% yield. The chlorohydrin was converted to R‐phenyloxirane‐[1‐14C], which was subsequently converted to the corresponding R‐cyanohydrin by reaction with TMS‐CN/CaO. Borane reduction and arylation, followed by salt formation yielded S‐γ‐[(4‐trifluoromethyl)phenoxy]benzenepropanamine‐[3‐14C] hydrochloride.
Enzymatic synthesis of [methyl‐2H3] creatinine
Authors: Arcelloni C. , Paroni R. , Bonini P. A. , Magni F. , Kienle M. Galli
Published: October 2006

2‐Amino‐1,5‐dihydro‐1‐[methyl‐2H3] 4H‐imidazol‐4‐one ([methyl‐2H3] creatinine) was obtained by acidification and heating (120 °C, 120 min) of the [methyl ‐2H3] N‐amidinosarcosine (creatine) synthesised by methylation of guanidoacetate (GA) with S‐adenosyl‐[methyl‐2H3] L‐methionine ([methyl‐2H3] AdoMet) in the presence of rat liver guanidoacetate methyltransferase (GAA‐MT). Isotopic enrichment was 94.7%.
[3H]imidacloprid: Synthesis of a candidate radioligand for the nicotinic acetylcholine receptor
Authors: Latli Bachir , Casida John E.
Published: October 2006

Imidacloprid is an exceptionally potent insecticide known from physiological studies to act at the nicotinic acetylcholine receptor. To prepare [3H]imidacloprid as a candidate radioligand, 6‐chloronicotinoyl chloride was reduced with NaB2H4 (in model studies) or NaB3H4 in absolute ethanol to 2‐chloro‐5‐pyridinylmethanol which was transformed to 2‐chloro‐5‐chloromethylpyridine on refluxing with thionyl chloride. Coupling with 4,5‐dihydro‐N‐nitro‐1H‐imidazol‐2‐amine then gave [2H2]imidacloprid incorporating about 95% of the deuterium or [3H2]imidacloprid (25 Ci/mmol) in 80% radiochemical yield. In studies not detailed here [3H]imidacloprid was found to undergo high affinity, specific and saturable binding to a site in insect brain.
Tc‐99m‐markierung von cymantren‐analogen verbindungen mit verschiedenen substituenten ‐ ein neuer zugang zu Tc‐99m radiodiagnostika
Authors: Wenzel M.
Published: October 2006

The Technetium‐analogues of Cymantrene derivatives containing different side chains can be labelled with Tc‐99m in a simple manner starting from labelled pertechnetate.

For the synthesis a solution of a ferrocene derivative with the wanted side chain, Tc 99m‐pertechnetate and a carbonyl‐donator like Mn(CO)5Br are heated at 150°C in a small glass vessel. There after the labelled cytectrene derivative is separated from by‐products by chromatographic methods. The radiochemical yields are between 15–95%. ‐ Some of the compounds showed a remarkable brain affinity with a high Tc‐99m‐concentration ratio brain/blood.
The synthesis of [14C]BRL 26830a, a novel β‐adrenoceptor agonist
Authors: Freer R. , Morecombe D. J.
Published: October 2006

BRL 26850A has been extensively reported 1 as a novel β‐adrenoceptor agonist. In order to perform metabolism studies, carbon‐14 radiolabelled BRL 26830A was synthesised from potassium [14C]cyanide. As BRL 26830A contains two asymmetric centres, the initial product required resolution of the two enantiomeric pairs. This was achieved by sequential fractional crystallisation of the free base and then the hydrobromide salt to obtain the required (R*, R*)‐(+) enantiomeric pair before final conversion to the hemifumarate salt ([14C]BRL 26830A).
Deuteriation of RS 87476
Authors: Souchet Michel , Pascal Jean Claude
Published: October 2006

Deuteriation of toluidine in 2H2O and synthesis of N‐[(d5‐phenyl phenyl)methyl] piperazine are described. These intermediates permit the incorporation of 7 deuterium atoms into RS 87476. This efficient synthesis of polydeuterated RS 87476 facilitated its use in preliminary animal studies and as an internal standard in RS 87476 quantification.
A convenient preparation of 3‐[2H3]methyl‐3‐buten‐1‐ol
Authors: Winter Rudolph Ernst K. , Jian Zhigang
Published: October 2006

A procedure for the conversion of 3‐hydroxy‐3‐methylglutaric anhydride to methyl 3‐methyl‐3‐butenoate forms the basis for a convenient synthesis of 3‐[2H3]methyl‐3‐buten‐1‐ol.
Synthesis of 2,3‐disubstituted [3‐13C]naphthalenes and [9a‐13C]naphtho[2,3‐d]‐1,2,3‐oxadiazole
Authors: Blocher Achim , Zeller Klaus‐Peter
Published: October 2006

The synthesis of 2‐amino‐2‐hydroxy[3‐13C]naphthalene starting from 2‐(1,3‐dioxolan‐2‐yl)‐benzyl chloride and sodium [13C]cyanide in seven preparative steps is reported. Diazotation of the labelled amino compound followed by deprotonation yields [9a‐13C]naphtho[2,3‐d]‐1,2,3‐oxadiazole. The β‐13C‐labelled naphthalenes prepared are characterized by their 13C‐chemical shifts and 13C13C spin spin coupling constants.
Synthesis of 9‐(2‐phosphonylmethoxy)ethyl‐8‐[14C]adenine [14C]PMEA
Authors: Haynes U. J. , Swigor J. E. , Bronson J. J.
Published: October 2006

The synthesis of [14C] PMEA (3) was achieved by coupling the sodium salt of 8‐[14C]adenine (1) with 2‐(diisopropyl‐phosphonymethoxy) ethanol methanesulfonate in N,N‐dimethylformamide at 100°C to provide the diisopropyl ester (2). Deesterification with bromotrimethylsilane in acetonitrile, followed by concentration and then aqueous hydrolysis of the resulting silylated intermediate produced [14C] PMEA (3) as a crystalline solid having a radiochemical purity of 99.1% and a specific activity of 88.7 μCi/mg in an overall yield of 30%.
Synthesis of [11C]‐ohmefentanyl, a novel, highly potent and selective agonist for opiate μ‐receptors
Authors: Zhu Y. C. , Prenant C. , Crouzel C. , Comar D. , Chi Z. Q.
Published: October 2006

The authors of the present paper reported the synthesis of [11C]‐ohmefentanyl in a symposium abstract in 1991(1). We here describe the results of synthesis and analysis in detail. Ohmefentanyl 1 is a novel, highly potent and selective agonist for opiate μ‐receptors. In order to visualize the μ‐receptor by Positron Emission Tomography (PET), this compound was labelled with carbon‐11. The unlabelled cis‐A‐ohmefentanyl was prepared in a nine‐step synthesis and two‐step fractional crystallization, and the OH‐precursor 11 for [11C]‐ohmefentanyl labelling was obtained by hydrolysis of the 4‐N‐propionyl group of cis‐A‐ohmefentanyl in 6 N hydrochloric acid. The [11C]‐propionyl chloride was prepared by carbonation of ethylmagnesium bromide with cyclotron‐produced [11C]‐carbon dioxide followed by direct treatment of the intermediate complex with phthaloyl dichloride and 2,6‐di‐t‐butylpyridine. Reaction of the OH‐precursor 11 with [11C]‐propionyl chloride yields [11C]‐ohmefentanyl separated by HPLC, with a high specific activity of 11.1 – 14.8 GBq μmol−1 (300−400 mCi μmol−1), 49 minutes after the end of bombardment.

The keto‐precursor 12, prepared by hydrolysis of the 4‐N‐propionyl group of cis‐10 in 8 N hydrochloric acid, was also used for [11C]‐ohmefentanyl labelling. Reaction of the [11C]‐propionyl chloride with keto‐precursor 12, followed by addition of sodium borohydride, yields [11C]‐ohmefentanyl.

The [11C]‐labelled ohmefentanyl obtained using the OH‐precursor 11 is a cis‐A form, while that obtained using the keto‐precursor is a mixture of cis‐A and cis‐B forms.
The preparation of a 11C‐labelled 5‐lipoxygenase product. 5(S)‐hydroxy‐6(R)‐(N‐[1‐11C]acetyl)cysteinyl‐7,9‐trans‐11,14‐ciseicosatetraenoic acid
Authors: Oberdorfer Franz , Siegel Thilo , Guhlmann Albrecht , Keppler Dietrich , Maier‐Borst Wolfgang
Published: October 2006

5(S)‐Hydroxy‐6(R)‐(N‐[1‐11C]acetyl)cysteinyl‐7,9‐trans‐11,14‐cis‐eicosatetraenoic acid (N‐[1‐11C]acetyl leukotriene E4) was prepared by the reaction of leukotriene E4 and [1‐11C]acetyl chloride. The product was obtained with 1.3% yield, based on [1‐11C]acetyl chloride. The preparation required 50 min from the end of radioisotope production. The chemical and radiochemical purity of an injectable dose of N‐[1‐11C]acetyl leukotriene E4 was 95%. The remaining impurities were the 11‐trans isomer primarily and the sulfoxides of 5(S)‐hydroxy‐6(R,S)‐(N‐[1‐11C]acetyl)cysteinyl‐7,9‐trans‐11‐(cis,trans)‐14‐cis‐eicosatetraenoic acid. The stereochemistry of the sulfoxides at C‐6 and at the C‐11 double bond respectively was not identified. The average specific activity of the carrier added preparation was 2 GBq/μmol at the time of application.
Synthesis of [16‐14C]trichodiene the precursor to trichothecenes
Authors: Zamir Lolita O. , Huang Liren
Published: October 2006

The synthesis of radiolabelled trichodiene with 14C at the olefinic methyl (C‐16) is described. The isotope was introduced using a 14C‐Wittig reagent prepared in situ from triphenyl phosphine and 14C‐methyliodide.
A convenient preparation of glycolic‐1‐14C acid
Authors: Clizbe Lane A. , Reist Elmer J.
Published: October 2006

An operationally simple preparation of glycolic‐1‐14C acid from 14CO2 has been developed using a tin‐lithium exchange reaction to generate the required hydroxymethyl anion equivalent. Glycolic‐1‐14C acid was then produced in high yield and good radiochemical purity upon hydrogenolytic removal of the benzyl group.
An improved synthesis of α‐13C glycine and heteronuclear NMR studies of its incorporation into thioredoxin
Authors: Wishart David S. , Sykes Brian D. , Richards Frederic M.
Published: October 2006

We present an improved method to easily prepare gram quantities of α‐13C glycine beginning from K13CN. The four step synthesis involves the production of an N, N‐diphenyl‐cyanoformamidine intermediate through the coupling of cyanide to N, N‐diphenylcarbodiimide. Subsequent reduction by LiAlH4 and hydrolysis of the resulting amidine produces fully enriched α‐13C labelled glycine with a 45‐50% yield. This relatively fast and simple synthesis uses only commonly available compounds and requires no special equipment, making the process easy to perform in any well equipped biochemistry laboratory. We further demonstrate that the product may be used, without extensive purification, to specifically label bacterially expressed proteins (E. coli thioredoxin) through standard biosynthetic procedures. We also show that the 13C glycine‐labelled protein may be readily analyzed using commonly available heteronuclear NMR techniques. Complete assignments for all 9 glycines of native E. coli thioredoxin are presented.
Synthesis of carbon‐14 and tritium labelled analogs of the noval antischizophrenic agent clozapine
Authors: Sunay Ustun B. , Talbot Kenrick C. , Galullo Vincent
Published: October 2006

8‐Chlor‐11‐(4‐methyl‐1‐piperazinyl)‐5H‐dibenzo[b,e][1,4]diazepine (SDZ 100‐129, Clozapine) labeled with carbon‐14 in the 11‐position was prepared from 2‐aminobenzonitrile‐[cyano‐14C]. In addition, SDZ 100‐129 was also labeled with C3H3 in the methyl group of the 4‐methyl‐piperazine ring.
Synthesis of 14C‐(carbonyl)‐N‐(4‐iodo‐2,6‐diethylphenylcarbamoylmethyl)‐iminodiacetic acid
Authors: Pozzi Oscar R. , Arciprete Carlos P. , Gros Eduardo G. , Mitta Aldo E. A.
Published: October 2006

The synthesis of the N‐(4‐iodo‐2,6‐diethylphenylcarbamoylmethyl) iminodiacetic acid labelled with 14C at the carbonyl carbon atom which was required for metabolism studies is described. The complex formation between the title product and Tc‐99m is also presented.
Preparation of 13C8 derivatives of naphthalene, octachloronaphthalene and two hexachloronaphthalenes
Authors: Auger P. , Malaiyandi M. , Wightman R. H. , Williams D. T.
Published: October 2006

A mild high yield sequence is reported for the synthesis of (13C8) naphthalene from (13C6) benzene and (13C2) succinic acid involving Friedel‐Crafts condensation, Wolff‐Kishner reduction, polyphosphoric acid cycliacylation, sodium borohydride reduction and palladium dehydrogenation. Perchlorination of (13C8) naphthalene gave a good yield of (13C8) octachloronaphthalene from which the (13C8) hexachloronaphthalenes were obtained by zinc/acetic acid reduction.
Synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone, an internal standard for analysis of tobacco‐specific nitrosamine hemoglobin and DNA adducts
Authors: Lin Jyh‐Ming , Amin Shantu , Murphy Sharon E. , Solomon Jerome J. , Hecht Stephen S.
Published: October 2006

The synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone ([3,3‐D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco‐specific nitrosamines, is reported. 3‐Pyridine carboxaldehyde was converted to 2‐(3‐pyridyl)‐1, 3‐dithiane. This was condensed with 2‐(2‐bromoethyl)‐1, 3‐dioxalane to yield 2‐[2‐(3‐pyridyl)‐1, 3‐dithiane]ethyl‐1, 3‐dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4‐(1, 3‐dithian‐2‐yl)‐4‐(3‐pyridyl)‐butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiAlH4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t–butyldimethylsilyl ether. Treatment with AgNO3/N‐chlorosuccinimide in aqueous CH3CN produced [3,3‐D2]HPB.
Synthesis and preliminary evaluation of an iodovinyl‐tetrabenazine analog as a marker for the vesicular monoamine transporter
Authors: Canney Daniel J. , Guo Yu‐Zhi , Kung Mei‐Ping , Kung Hank F.
Published: October 2006

A derivative of tetrabenazine (TBZ, 1) containing an iodovinyl group (I‐TBZ, 3b) was prepared as a potential radiotracer for the vesicular monoamine transporter. The synthesis of 3a was achieved by ethynylation of TBZ. The ethynyl derivative 4, was converted to the corresponding vinylstannane 5. The vinylstannane intermediate was then treated with I2 in chloroform at room temperature, to afford the iodovinyl compound (3a, I‐TBZ). The no‐carrier‐added [125I]I‐TBZ (3b) was prepared by treating an ethanolic solution of 5 with sodium[125I]iodide in the presence of H2O2. Following i.v. injection, [125I]I‐TBZ (3b) can readily cross the blood brain barrier and localize in the brain (0.92 and 0.36% dose/organ, at 2 min and 30 min, respectively). However, no specific regional uptake of the ligand was observed. Subsequent biodistribution studies performed using two well resolved peaks obtained from chiral HPLC separation of 3b, demonstrated that Fraction I displayed higher brain uptake (0.6% dose/organ, 20 min) than the latter peak (Fraction II, 0.3% dose/organ, 20 min). Fraction I also exhibited a modest degree of specificity for the striatum which could be blocked by pretreatment with tetrabenazine. The high lipophilicity of 3a (Po/b for Fraction 1 and II=1723 and 1395, respectively) may contribute to high nonspecific binding in vivo, and result in the low target/nontarget ratio observed for this compound. Iodovinyl‐TBZ analog 3b is a poor candidate as a SPECT imaging agent for the vesicular monoamine transporter.
True tracer radiolabeling of gadolinium complex of 10‐(2‐hydroxypropyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7 triacetic acid (HP‐DO3A)
Authors: Kumar Krishan , Sukumaran K. , Chang C. Allen , Tweedle M. F. , Eckelman W. C.
Published: October 2006

True tracer radiolabeling, purification, and analysis of a gadolinium complex of HP‐DO3A (10‐(2‐hydroxy‐propyl)‐1,4,7,10‐tetraazacyclo dodecane‐1,4,7‐triacetic acid) was achieved by the reaction of carrier‐added 153GdCl3 and excess free ligand. Two analytical methods (ITLC and HPLC) were developed to determine the purity of radiolabeled samples.
The preparation of tritiated E‐ and Z‐4‐aminobut‐2‐enoic acids, conformationally restricted analogues of the inhibitory neurotransmitter 4‐aminobutanoic acid (GABA)
Authors: Duke Rujee K. , Allan Robin D. , Drew Colleen A. , Johnston Graham A. R. , Mewett Kenneth N. , Long Mervyn A. , Than Chit
Published: October 2006

A synthesis of [3H]E‐ and [3H]Z‐4‐aminobut‐2‐enoic acids from methyl 4‐N‐phthalimidobut‐2‐ynoate by catalytic hydrogenation using tritium gas in the presence of a homogeneous catalyst, tris(triphenylphosphine)rhodium(I) chloride, is reported. HPLC separation of the E‐ and Z‐isomers, and the saturated analogue, 4‐aminobutanoic acid (GABA), is also described.
Synthesis of novel [14C]‐labelled phenylureas bearing photoactive azido and diazirine groups as photoaffinity labels for the herbicide binding site of photosystem two
Authors: Jewess Philip , Whitelegge Julian P. , Camilleri Patrick , Bowyer John R.
Published: October 2006

We have synthesised two photoaffinity‐labelling hydrophobic stilbene urea inhibitors of Photosystem 2 (PS2) bearing either an azido group (3‐(3‐((E)2‐(4‐azidophenyl)ethenyl)‐phenyl)‐1,1‐dimethylurea, azido‐PDU) or a diazirine group (3‐(3‐((E)2‐(4‐(3‐(trifluoromethyl)‐diazirin‐3‐yl)phenyl)ethenyl)phenyl)‐1,1‐dimethylurea, diazirinyl‐PDU) as well as [14C]‐labelled forms of these compounds. The key step in both syntheses was the formation of the stilbene entity by a Waddsworth‐Emmons reaction of either a trifluoroacetyl‐protected aminobenzaldehyde or a 3‐(trifluoromethyl)‐diazirin‐3‐yl‐substituted benzaldehyde with dimethyl(4‐nitrophenylmethyl)‐phosphonate which gave largely E stereochemistry. The latter compound was made from 4‐bromobenzaldehyde protected as the 1,3 dioxolane. The substituted diazirine was then constructed via Grignard chemistry and an adaptation of a published procedure for the synthesis of diazirines. Reduction of the nitrostilbenes to the respective anilines and conversion to the isocyanates followed by reaction with di[14C]methylamine then gave the required [14C]‐labelled phenylurea photoaffinity reagents. In studies not detailed here both reagents were found to be highly active inhibitors of photosynthetic electron transport before UV irradiation and to covalently label the herbicidebinding protein (D1) of Photosystem 2 after UV treatment. Diazirinyl‐PDU was found to be considerably more sensitive to UV irradiation than azido‐PDU.
Synthesis and spectroscopic characterisation of 3‐chloroperbenzoic acid‐17O,18O, nitrosobenzene‐17O,18O and nitrosobenzene‐15N
Authors: Bleasdale Christine , Ellis Martin K. , Farmer Peter B. , Golding Bernard T. , Handley Kevin F. , Jones Peter , McFarlane William
Published: October 2006

3‐Chloroperbenzoic acid‐17O,18O was prepared from 3‐chlorobenzoyl chloride and hydrogen peroxide‐17O,18O (obtained by subjecting water‐17O,18O. Nitrobenzene‐15N was reduced to aniline‐15N, which was oxidised by 3‐chloroperbenzoic acid to nitrosobenzene‐15N. 15N and 17O NMR data are given for the corresponding labelled nitrosobenzene.
Synthesis of 7‐[α‐(2‐amino‐[2‐14C]thiazol‐4‐yl)‐α‐(Z)‐methoxyiminoacetamido]‐3‐(1‐methylpyrrolidinio)methyl‐3‐cephem‐4‐carboxylate hydrochloride ([14C]cefepime hydrochloride)
Authors: Standridge R. T. , Swigor J. E.
Published: October 2006

The title compound 9 was prepared by the route outlined in Scheme I. [14C]Thiourea (1) was condensed with ethyl 4‐bromo‐3‐oxo‐2‐methoxyiminoacetate (2), providing ethyl 2‐(2‐amino‐4‐[2‐14C]thiazolyl)‐2‐methoxyiminoacetate (3), as the pure Z‐isomer. Saponification gave the amino acid 4; this was reacted with 1‐hydroxybenzotriazole to give the activated ester 5. Condensation in situ with 7‐amino‐3‐(1‐methylpyrrolidinio) methyl‐3‐cephem‐4‐carboxylate (6) yielded the product as the pure sulfate salt (7).

Treatment of 7 with base provided the zwitterion 8, isolated as the stable N‐methyl‐2‐pyrrolidinone adduct. An aqueous solution of the adduct was converted to the crystalline title compound, [14C]Cefepime hydrochloride hydrate (9), with hydrochloric acid/acetone. Radiochemical purity was 99.0% and specific activity, 34.2 μCi/mg. Overall yield from [14C]thiourea was 18%.
The synthesis and resolution of tritiated 4‐amino‐3‐phenylbutanoic acid ([3H]R‐ and [3H]S‐β‐phenylgaba)
Authors: Duke Rujee K. , Allan Robin D. , Drew Colleen A. , Johnston Graham A. R. , Mewett Kenneth N. , Long Mervyn A. , Than Chit
Published: October 2006

A synthesis of [3H]R‐ and [3H]S‐4‐amino‐3‐phenylbutanoic acid ([3H]R‐ and [3H]S‐β‐phenylGABA) from the unsaturated intermediate by catalytic hydrogenation using tritium gas in the presence of palladium on charcoal is reported. The [3H]R‐ and [3H]S‐diastereoisomers of pantolactone ester of β‐phenylGABA were separated by HPLC.
Synthesis of fluoro‐dideutero‐methyl 1,1,1,3,3,3‐hexafluoro‐2‐propyl ether (deuterated sevoflurane)
Authors: Baker Max T. , Chiang Chao‐Kuo , Tinker John H.
Published: October 2006

Sevoflurane was synthesized with deuterium substituents on the fluoromethoxy carbon. This was performed by a two‐step reaction process that yielded deuterated sevoflurane of high purity.
Synthesis of position‐specific tritium‐labeled 20(S)‐camptothecin, 9‐amino‐20(S)‐camptothecin, and 10,11‐methylenedioxy‐20(S)‐camptothecin
Authors: Nicholas Allan W. , Wani Mansukh C. , Wall Monroe E. , Kepler John A. , Taylor George F.
Published: October 2006

The synthesis is given for three ring A tritiated camptothecin (CPT) analogs as biological probes in the study of the parent compounds which are of current widespread interest as potent anticancer agents. The strategy of catalytic tritolysis of aryl halide bonds was employed, and thus the preparations of the requisite precursors 9‐chloro‐20(S)‐CPT (9), 9‐amino‐10,12‐dibromo‐20(S)‐CPT (14), and 9‐chloro‐10,11‐methylenedioxy‐20(S)‐CPT (18) are given; catalytic tritiation of these respective precursors under polar, alkaline solvent conditions using palladium/carbon provides smooth conversion to [9‐3H]‐20(S)‐CPT (10), 9‐amino‐[10,12‐3H]‐20(S)‐CPT (15), and [9‐3H]‐10,11‐methylenedioxy‐20(S)‐CPT (19).
Synthesis of [11C] platelet‐activating factor (PAF) analogs for in vivo imaging of PAF receptors
Authors: Sasaki T. , Karasawa K. , Ishiwata K. , Satoh N. , Ishii S. , Ogawa K. , Nozaki T. , Setaka M. , Nojima S. , Senda M.
Published: October 2006

1‐O‐Hexadecyl‐2‐O‐N, N‐dimethylcarbamoyl‐sn‐glycero‐3‐phosphocholine[choline methyl‐11C] ([11C]dimethylcarbamoyl‐PAF) and 1‐O‐Hexadecyl‐2‐O‐acetyl‐sn‐glycero‐3‐phosphocholine[choline methyl‐11C] ([11C]C16‐PAF) were synthesized as follows; Each of non‐labeled dimethylcarbamoyl‐PAF and C16‐PAF was treated with sodium benzene thiolate to derive their desmethyl‐precursors containing a dimethylphosphoethanolamine at sn‐3. 11C‐Labeled dimethylcarbamoyl‐PAF and C16‐PAF were synthesized by methylation of the respective desmethyl‐precursors using [11C]CH3I. The radiochemical yield of methylation in [11C]dimethylcarbamoyl‐PAF and [11C]C16‐PAF was about 15 and 10% (decay corrected), respectively. The lower yield of [11C]C16‐PAF compared with that of [11C]dimethylcarbamoyl‐PAF was attributed to hydrolysis of the 2‐acetyl group of [11C]C16‐PAF during methylation. To study the stability to enzymatic hydrolysis, [11C]dimethylcarbamoyl‐PAF or [11C]C16‐PAF was incubated with mouse plasma at 37 °C.
Synthesis of [3H]cyfluthrin
Authors: Pleiß Ulrich , Römer Johannes , Thomas Rudolf
Published: October 2006

For the elucidation of the distribution and biotransformation of Cyfluthrin in tse‐tse flies the tritium‐labelled compound was needed. A brominated precursor was dehalogenated with tritium gas using a special noble metal catalyst to give the desired [3H]Cyfluthrin. The labelling position was confirmed by 3H‐NMR spectroscopy. After synthesis and purification, the [3H]Cyfluthrin obtained showed a specific activity of 23.7 Ci/ mmol (877 GBq/mmol).
Synthesis and labelling characteristics of 99mTc‐mercaptoacetyltripeptides
Authors: Bormans G. , Cleynhens B. , Adriaens P. , de Roo M. , Verbruggen A.
Published: October 2006

A number of derivatives of mercaptoacetyltriglycine in which one or more of the three glycylmoieties are replaced by other amino acids such as D‐ or L‐alanine, D‐serine, D‐2‐aminobutyric acid, D‐valine or D‐phenylglycine have been synthesized and labelled with technetium‐99m.

Labelling with technetium yielded in each a mixture of mainly two radioactive species, which probably are diastereomeric oxotechnetium (V) complexes originating from the presence of a chiral carbon atom in the ligands. The diastereomers were separated by reversed phase HPLC. Except for the serine derivative, all radiolabelled derivatives have a longer retention time than the parent compound 99mTc‐MAG3. The relative amount of the two diastereomers formed upon labelling is dependent on the nature of the ligand but can be influenced to a limited extent by the pH of the exchange labelling mixture.
Marquage PAR 14C et 13C du terbutylanilino‐4 chloroethyluree
Authors: Azim M. , Madelmont J. C. , Cussac C. , Rapp M. , Maurizis J. C. , G.‐Gaudreault R. , Godeneche D. , Veyre A.
Published: October 2006

Le 2‐chloroethy isocyanate a été marqué par 14C ou 13C sur le groupe carbonyl à partir de l'acide 3‐chloropropionique 14C ou 13C afin de réaliser le marquage du 4‐terbutyl [3‐(2‐chloroethyl ureido] benzene).
Synthesis of the anti‐tumor agent CI‐973 {[SP‐4‐3‐(R)]‐[1,1‐cyclobutanedicarboxylato(2)](2‐methyl‐1,4‐[4‐14C]butanediamine‐N,N′)platinum}
Authors: Ekhato I. Victor , Hoeschele James D. , Huang Che C. , Nanavaty Bela , Lee Helen T.
Published: October 2006

Starting from the chiral compound 1, (R)‐(+)‐2‐methyl‐1,4‐[14C]butanediamine 7 was synthesized in a sequence of reactions in which 14C‐label was introduce using label potassium cyanide. Compound 7 was reacted with potassium tetraiodoplatinate and silver 1,1‐cyclobutanedicarboxylate to make the title compound {[SP‐4‐3‐(R)]‐[1,1‐cyclobutanedicarboxylato(2)](2‐methyl‐1,4‐butanediamine‐N,N′)platinum} 11.
Synthese d'un telomere perfluorocarbone derive du tris‐(hydroxymethyl) 14C et 13C‐acrylamidomethane (F‐TAC)
Authors: Azim M. , Madelmont J. C. , Rapp M. , Maurizis J. C. , Pavia A. , Pucci B. , Veyre A.
Published: October 2006

Le télomère perfluoré F5TAC5 a été marqué par 14C et 13C sur le groupe carbonyle à partir de l'acide acrylique 14C. La synthèse est réalisée en cinq étapes à partir de BaCO3 comme précurseur. Le rendement de marquage calculé par rapport au précurseur (Ba14CO2 ou 13CO3) est de l'ordre de 25 à 30%.
Synthesis of [21‐13C]‐cholesterol
Authors: Caballero Gerardo M. , Gros Eduardo G.
Published: October 2006

The synthesis of [21‐13C]‐cholesterol (5) from 3β‐O‐(t‐butyldimethylsilyl)‐17β‐cyano‐androst‐5‐ene (1) is described. Labelled carbon‐atom was introduced by Grignard reaction of nitrile derivative with [13C]‐methylmagnesium iodide. Location of label was confirmed by 13C‐NMR spectroscopy.
Synthesis of [N‐C3H3]‐trans‐(1R,3S)‐(−)‐1‐Phenyl‐3‐N,N‐dimethylamino‐1,2,3,4‐tetrahydronaphthalene (H2‐PAT)
Authors: Wyrick Steven D. , Myers Andrew M. , Booth Raymond G. , Kula Nora S. , Baldessarini Ross J. , Mailman Richard B.
Published: October 2006

Subsequent to the discovery that the (+)‐benzomorphan sigma receptor ligands, (+)‐pentazocine and (+)‐N‐allylnormetazocine, stimulated tyrosine hydroxylase activity and dopamine synthesis in rat striatum in vitro, we reported a similar effect on a structurally similar series of 1‐phenyl‐3‐aminotetrahydronaphthalenes (phenylaminotetralins, PAT's). Both racemic 1‐phenyl‐3‐dimethylamino‐6‐chloro‐7‐hydroxytetralin (CI,OH‐PAT) and racemic 1‐phenyl‐3‐dimethylaminotetralin (H2‐PAT) stimulated tyrosine hydroxylase with an EC50 of approximately 0.1 μM. The former was also found to have a non‐specific dopamine releasing effect while the latter was devoid of such activity affording it the less complicated pharmacological profile of the two analogs. We previously reported the synthesis of tritium labeled Cl,OH‐PAT to be used in radioreceptor and autoradiography studies and found that it labeled a sigma‐like site in guinea pig brain with an apparent Kd of ∼50 pM and with a pharmacological profile unique from other known CNS receptors. Here we report the synthesis of high specific activity tritium labeled trans‐(1R,3S)‐(−)‐H2‐PAT as this enantiomer was found to be more active in the tyrosine hydroxylase assay and possessed approximately 45 fold greater affinity for the novel neuromodulatory sigma‐like receptor.
Synthesis of 8‐[18O]hydroxy‐2′‐deoxyguanosine
Authors: Hermanns R. C. A. , Zomer G. , Jacquemijns M. , Stavenuiter J. F. C. , Westra J. G. , Teixeira A. J. R. , Van De Werken G.
Published: October 2006

8‐[18O]Hydroxy‐2′‐deoxyguanosine was synthesized starting from 8‐bromo‐2′‐deoxyguanosine and the sodium salt of [18O]benzyl alcohol, resulting in the intermediate 8‐[18O]benzyloxy‐2′‐deoxyguanosine. Subsequent reduction by catalytic transfer hydrogenation, yielded the desired product 8‐[18O]hydroxy‐2′‐deoxyguanosine.

8‐Bromo‐2′‐deoxyguanosine was synthesized from 2′‐deoxyguanosine by treatment with Br2. The sodium salt of [18O]benzyl alcohol was prepared by treatment of ethyl benzimidate hydrochloride with H218O (95%), LiAlH4 and sodium hydride. Starting from H218O the overall yield of 8‐[18O]hydroxy‐2′‐deoxyguanosine was approximately 4%. The isotopic purity was calculated to be 93.4 atom% based on GC‐MS measurements. The chemical purity and the isotopic purity comply with the planned application, namely as internal standard for the determination of 8‐hydroxy‐2′‐deoxyguanosine by GC‐MS.
Synthesis of sodium 6‐isopropyl‐3‐[4‐(P‐chlorobenzenesulfonylamino)‐butyl]‐[2‐14C]azulene‐1‐sulfonate
Authors: Yanagisawa Takashi , Yokota Masayuki , Tomiyama Tsuyoshi , Ikegami Shiro
Published: October 2006

Sodium 6‐isopropyl‐3‐[4‐(p‐chlorobenzenesulfonylamino)‐butyl]azulene‐l‐sulfonate (KT2‐962)1, which has been found to be a potent and selective thromboxaneA2receptor antagonist, was synthesized in14C‐labelled form by using potassium [14C]‐cyanide.

14C‐labelled1with a specific activity of 2.36 GBq/mmol was prepared with no‐carrier‐added and in nine steps in 64% overall radiochemical yield.
Synthesis of bisaramil labelled with carbon‐14 and deuterium
Authors: Szammer J. , Simon‐Trompler E. , Mlinko S.
Published: October 2006

[6,8‐14C2]‐Bisaramil: 3‐methyl‐7‐ethyl‐9α‐(4‐chlorobenzoyloxy)‐3,7‐diazabicyclo/3.3.1./nonane‐[6,8‐14C2] monohydrochloride and [7‐N‐D5‐ethyl]‐Bisaramil: 3‐methyl‐7‐[D5‐ethyl]‐9α‐(4‐chlorobenzoyloxy)‐3,7‐diazabicyclo/3.3.1./nonane monohydrochloride were synthesized in four steps from 14CO2 (6% overall yield) and in six steps from [D6]‐ethanol (4% overall yield), respectively.
99m‐technetium labelling of a tumor associated murine monoclonal antibody for immunoscintigraphic studies in man
Authors: Archimandritis Spyridon C. , Malamitsi Julia , Belkas Elias , Varvarigou Alexandra D. , Cotsyfakis Kyriakos , Sivolapenko Gregory , Zorzos John , Skarlos Demosthenes V. , Proukakis Charalambos
Published: October 2006

The present study refers to the preparation of a 99m‐Technetium labelled murine monoclonal antibody for clinical application. The monoclonal antibody was incubated with a 20fold molar excess of 2‐iminothiolane. The free thiol groups created, were capable of binding reduced technetium. Labelling took place through an exchange reaction with 99m‐Technetium‐Glucoheptonate. The labelling conditions were studied extensively. Diverse chromatographic methods (ITLC, HPLC) were developed in order to study the radiochemical behaviour of the labelled antibody and evaluate the labelling efficiency and the in vitro stability. Results on the labelling technique and on the quality control methods are presented, as well as preliminary immunoscintigraphic data.
In vivo pharmacokinetics of [14C]‐etanidazole
Authors: Breccia Alberto , Gattavecchia Enrico , Feroci Giorgio , Fini Adamo , Busutti Luciano
Published: October 2006

Etanidazole, like other nitroaromatic radio sensitizers, displays its biological activity mostly through two molecular groups: the nitro group and the side‐chain attached to the nitrogen in the imidazole ring in position 1.

To monitor the behaviour of the two moieties in vivo, labelled Etanidazole, containing a 14C atom in position 2 of the side‐chain was prepared and administered to four patients at a 2 gm−2 dose: the concentration of Etanidazole in different fluids and tissues was followed either by titrating the NO2 group by polarography or determining the total radioactivity, carried by the side‐chain. Two different profiles of Etanidazole concentration were found, in blood and urine, as determined by the two methods. The concentration was found to be higher when measured as total radioactivity than when measured by polarography; this difference was greater in blood (49%) than in urine (27%). Since the two methods involve determination of different portions of the Etanidazole molecule, we hypothesized a degradation of the drug to explain these differences.
Synthesis of [2,4‐3H] 17β‐dihydroequilin sulfate
Authors: Bhavnani Bhagu R.
Published: October 2006

[2,4‐3H] 17β‐dihydroequilin‐3‐sulfate ammonium salt suitable for in vivo pharmacokinetic studies was synthesized from [2,4‐3H] equillin. Sulfation of [2,4‐3H] equillin with pyridine‐chiorosulfonic acid mixture gave in high yields [2,4‐3H] equilin sulfate, which was then reduced with sodium borohydride to yield [2,4‐3H] 17β‐dihydroequilin sulfate. The reduction was sterospecific and no 17α‐reduced products were formed.
Synthesis of [19‐11C]arachidonic acid
Authors: Kihlberg Tor , Långström Bengt
Published: October 2006

The preparation of (all Z)‐1,17‐dichloro‐4,7,10,13‐heptadecatetraene is reported. The synthesis was performed in five steps with a total yield of 22 %, starting from 5‐chloro‐1‐pentyne. The corresponding bis Grignard reagent was used in a copper‐mediated coupling reaction with [1‐11C]ethyl iodide followed by a carbonation with CO2 to afford [19‐11C]arachidonic acid in 23 % decay corrected radiochemical yield within 52 min. The radiochemical purity of the final product was 98 %. In a typical run starting with 20 GBq [11C]O2, 760 MBq of [19‐11C]arachidonic acid was obtained, with a specific activity of 1.6 GBq/μmol.
Preparation of high molecular weight radioiodinated alginic acid
Authors: Orlando P. , Binaglia L. , De Feo A. , Trevisi R. , Melodia C. , Trenta R.
Published: October 2006

A simple procedure is described for preparing125I‐labelled alginic acid. The reducing terminal of alginic acid is derivatized with tyramine through the formation of Schiff base which is subsequently reduced with sodium cyanoborohydride. By radioiodination of the aromatic ring introduced,125I‐labelled alginic acid was obtained with high specific activity.
Synthesis of 2‐methyl‐2‐[[(7‐methyl‐7H‐benzo[c]carbazol‐10‐yl)[14C]methyl[amino]‐1,3‐propanediol mesylate — a potential antitumor agent
Authors: Hill John A. , Eaddy John F.
Published: October 2006

2‐Methyl‐2‐[[(7‐methyl‐7H‐benzo[c]carbazol‐10‐yl)methyl]amino]‐1,3‐propanediol (1, 7U85) was synthesized as the mesylate salt in the [14C]‐labelled form with specific activity 48.4 mCi/mmol suitable for metabolism and tissue distribution studies in animals The synthetic sequence involved the regiospecific synthesis of a bromobenzo[c]carbazole by a modified Fischer indole synthesis, formylation by a Bouveault reaction, and reductive amination. The radiochemical purity was > 97.3%.