bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of the effect of the quantity of stannous ion on the quality of technetium‐99m labelled albumin
Authors: Billinghurst M. W. , Rempel S. , Westendorf B. A.
Published: October 2006

The importance of maintaining a low ratio of stannous ion to albumin molecules in order to obtain a high quality technetium‐99m labelled albumin is demonstrated. It is further shown that the direct preparation of technetium‐99m albumin by reduction of the technetium‐99mm pertechnetate with stannous ion inevitably leads to the contamination of the product with a certain amount of tin colloid which is also labelled with technetium‐99m. It is demonstrated that this can be avoided by utilizing labelling techniques involving the initial formation of other technetium chelates which are less stable than the albumin complex under certain conditions, adding the albumin to that preparation, adjusting the conditions and thus allowing the albumin to become labelled with technetium‐99m via an exchange with the original chelating agent.
Synthesis, chromatography and tissue distribution of 1‐[11 C]‐hexobarbital
Authors: Kloster G. , Müller‐Platz C.
Published: October 2006

1‐[11C]‐Hexobarbital was synthetized by methylation of norhexobarbital using 11CH3I. The maximum radiochemical yield after purification by hplc is 47% at a specific activity of 1.0 mCi/μmole. Synthesis time including purification is 37 min. The tissue distribution was determined in mice at different times after i.v. injection. The main accumulation of activity during the first hour after i.v. injection is in liver and kidneys. Other well perfused organs like brain, heart and lung show significant accumulation only during the first minutes after injection.
Preparation of 5‐amino‐3,4‐bipyridin‐6(1H)‐one‐514C. A new cardiotonic agent
Authors: Gubitz Franklyn W.
Published: October 2006

Inocor™ brand of amrinone1 (5‐amino‐3,4‐bipyridin‐6(1H)‐one‐514C) a new positive inotropic agent was obtained [14C] labelled at Carbon 5 in 55% overall yield.
Preparation of 14C‐labelled poly(ℓ‐menthyl isopropenyl carbonates)
Authors: Comes Roger A. , Grubbs Harvey J.
Published: October 2006

The synthesis of 14C‐labelled poly(ℓ‐menthyl isopropenyl carbonate) is described. Experimental conditions are included for incorporation of 14C into each of the carbon atoms in the molecule. High pressure liquid chromatography conditions are given for separation and purification of the labelled intermediates.
Syntheses of N‐[1‐2H]‐ and N‐[1‐3H]‐cyclopropylbenzylamine and [phenyl‐14C]‐N‐cyclopropylbenzylamine
Authors: Silverman Richard B. , Hoffman Stephen J.
Published: October 2006

N‐[1‐2H]‐ (5a) and N‐[1‐3H]‐Cyclopropylbenzylamine (5b) were synthesized from cyclopropanecarbonitrile. The α‐proton of cyclopropanecarbonitrile was exchanged in [O‐2H]‐ and [O‐3H]‐methanol using sodium methoxide as the base. [α‐2H]‐ and [α‐3H]‐Cyclopropanecarbonitrile were hydrolyzed in 4N HCl to the α‐labeled cyclopropanecarboxylic acids which were converted to [1‐2H]‐ and [1‐3H]‐cyclopropylamine. HCl by Curtius rearrangements. The labeled cyclopropylamines were benzylated by reaction with benzaldehyde followed by sodium cyanoborohydride reduction. [phenyl‐14C]‐Cyclopropylbenzylamine (2b) was prepared by the reaction of cyclopropylamine with [phenyl‐14C] benzaldehyde followed by sodium cyanoborohydride reduction.
Potential drugs labelled with 14C. I. The synthesis of 3‐benzylamino‐5, 6‐dihydro‐8, 9‐dimethoxy‐imidazo [5,1‐a] isoquinoline hydrochloride
Authors: Zólyomi G. , Koltai E. , Bánfi D. , Harsányi K.
Published: October 2006

3‐Benzylamino‐8, 9‐dimethoxy‐5, 6‐dihydro‐imidazo‐ [5,1‐a] isoquinoline hydrochloride was labelled with 14C in two different positions: In one case the 14C was built into the position 2 of the imidazole ring, in the other case into the position 3 of the isoquinoline ring. In the first case the mechanism of the halogen‐cyano exchange reaction of 1‐chloromethyl‐5, 6‐dimethoxy‐3, 4‐dihydro‐isoquinoline was investigated by tracer experiments.
Preparation of 1‐[14C] hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone (EG‐626)
Authors: Abuki Hideo , Miyazaki Hiroshi
Published: October 2006

1‐[14C] Hydroxymethyl‐6‐ethoxycarbonyl‐5,7‐dimethyl‐4‐phthalazone ([14C] EG‐626, 12) was synthesised from 6‐ethoxy‐carbonyl‐5,7‐dimethyl‐4‐methoxyphthalazine‐2‐N‐oxide (8) and potassium [14C] cyanide by the Reissert‐Henze reaction.

The overall radiochemical yield from potassium [14C] cyanide was 21.0 %.
Synthesis of deuterium enriched L‐glutamine and 4‐aminobutanamide from pyridazinones
Authors: Stogniew Martin , Geelhaar Linda A. , Callery Patrick S.
Published: October 2006

A convenient method is presented for the preparation of the amino acid glutamine and its decarboxylation product 4‐amino‐ butanamide (GABAMIDE) enriched with deuterium. In a single step, 6‐carboxy‐3(2H)‐pyridazinone was reduced with deuterium gas to give racemic glutamine‐2,3,4‐2H3. L‐Glutamine‐2,3,4‐2H3 was prepared by the stereospecific deacetylation of N2‐acetylglutamine‐2,3,4‐2H3 with acylase I. 4‐Aminobutanamide‐2,3,4‐2H3 was synthesized from 3(2H)‐pyridazinone in two steps. Reduction of 3(2H)‐pyridazinone with deuterium gas gave the intermediate, 1,4,5,6‐tetrahydro‐3(2H)‐pyridazinone‐4,5,6‐2H3, which was further reduced with Raney nickel and hydrogen to yield 4‐aminobutanamide‐2,3,4‐2H3.
Determination of inorganic radioiodine in solutions of 125I‐labelled proteins
Authors: Siuda Anjrzej , Łucka Barbara
Published: October 2006

A rapid paper chromatography procedure using 33% w/v aqueous solution of ammonium sulphate as a solvent has been applied for routine determination of the proportion of 1251 present inorganic iodine in solutions containing 125I‐labelled proteins. Rf values for protein, iodide and iodate correspond to 0.0, 0.5, and 0.9, respectively.

The amount of inorganic iodine in the iodination mixture or in the iodinated protein preparation can be determined with good precision in less than 30 minutes.
Synthesis of 2‐(bromomethyl‐13C)‐fumaric acid (bromomesaconic acid)
Authors: Aberhart D. John , Hsu Chi‐Tung
Published: October 2006

The fumarase inhibitor, bromomescaconic acid, has been synthesized with 13C labeling in the bromomethyl group. Di‐t‐butyl acetylene‐dicarboxylate was converted with Li (13CH3)2Cu to di‐t‐butyl (methyl‐13C)citraconate. Photochemical isomerization of this to di‐t‐butyl (methyl‐13C)mesaconate, followed by deblocking with trifluoroacetic acid gave the title compound.
Synthese de l'indazole‐1‐15N, de l'indazole‐2‐15N et de leurs derives n‐methyles
Authors: Pellegrin Valdo , Fruchier Alain , Elguero José
Published: October 2006

The synthesis of indazole‐1‐15N from 2‐nitrotoluene‐15N is described Indazole‐2‐15N has been prepared from 2‐methyl‐4‐nitroaniline and sodium nitrite‐15N through 5‐nitroindazole‐2‐15N. The N‐methyl derivatives of these three indazoles have been isolated.
Synthesis of 2,9‐[14C]Dimethyl‐1, 10‐phenanthroline and the production of 67Cu
Authors: Smit H. , Vis R. D. , Pijper F. J. , van der Goot H. , de Bolster M. W. G.
Published: October 2006

2,9‐[14C]Dimethyl‐1,10‐phenanthroline was prepared by means of a nucleophilic methylation of 2‐methyl‐1,10‐phenanthroline with [14c]methyllithium followed by oxidation. The specific activity of the synthesized and purified 2,9‐[14C]dimethyl‐1,10‐phenanthroline was 1.78 mCi/mmol. The overall radiochemical yield was 59%.

67Cu was produced by α‐bombardment of 64Ni.
Etude de la deuteration du decane
Authors: Bouchet P. , Lazaro R. , Rouviere J.
Published: October 2006

In view of small angle neutronic diffusion studies of polyphasic systems we need n‐decane totally and/or partially deuterated. Deuteration by isotopic exchange over Pd/c catalyst has been already studied (1‐3). We have optimized the patented process (3) so that the yield of exchange has been brought up from 9% to 30%. The deuteration amount has been measured by three different ways: Mass and NMR spectrometry and densimetry. For the statistically partially deuterated samples, Mass spectroscopy is a very interesting tool.
Synthesis of glycolic‐d2 acid
Authors: Ramesh S.
Published: October 2006

Glycolic‐d2 acid, HOCD2 CO2H, was prepared by the Cannizzarorearrangement of glyoxal‐d2 and by the action of nitrous acid on glycine‐d5.
A convenient synthesis of carbon labeled adenine nucleotides: Adenosine‐2‐13C 5′ ‐phosphate
Authors: Meyer Rich B. , Wong Corinne G.
Published: October 2006

Treatment of adenosine 5′‐phosphate 1‐oxide with base gave 5‐amino‐1‐β‐ D‐ribofuranosylimidazole‐4‐carboxamidoxime 5′‐ phosphate. Catalytic reduction of this amidoxime gave the versatile intermediate, 5‐amino‐1‐β‐D‐ribofuranosylimidazole‐ 4‐carboxamidine 5′‐phosphate. Condensation of this nucleo‐ tide with formaldehyde‐13C in the presence of palladium provided a simple preparation of adenosine‐2‐13C 5′‐phosphate.
Tritiated peptides. Part 101. Catalytic exchange labelling of β‐corticotrophin‐ (1‐24) ‐tetracosapeptide
Authors: Brundish Derek E. , Wade Roy
Published: October 2006

β‐Corticotrophin‐ (1‐24) ‐tetracosapeptide

β‐Corticotrophin‐(1‐24)‐tetracosapeptide: tetracosactrin, Synacthen® (trade name of CIBA‐GEIGY Basle) Ser‐Tyr‐Ser‐Met‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐Lys‐Pro‐Val‐Gly‐Lys‐Lys‐Arg‐Arg‐Pro‐Val‐Lys‐Val‐Tyr‐Pro.

was labelled to a level of 0.48 Ci mmol−1 by catalytic exchange of a protected synthetic precursor with tritium gas. Over 80% of the isotope was incorporated into acid‐stable sites in the histidine residue. Smaller amounts were incorporated into methionine (5%), tyrosine (3%), phenylalanine (5%) and tryptophan (2%). Aminobutyric acid was formed (1%) by degradation of methionine and had incorporated tritium (5%). The labelled amino acid residues were stereochemically pure within the limits of experimental error.
Labelled psoralens. Synthesis of 4′‐aminomethyltrioxsalen‐3‐t
Authors: Liebman Arnold A. , Delaney Charles M.
Published: October 2006

Bromination of 4′‐phthalimidomethyltrioxsalen (3) provided the 3‐monobromo derivative (4) which on hydrogenolysis with either deuterium or tritium provided the corresponding labelled derivatives 5 and 6. Removal of the phthalimide moiety from 6 produced the title compound (9) having specific activity of 7.46 Ci/mmole.
Synthesis of [7‐3H]‐3β, 16β‐dihydoxy‐5‐androsten‐17‐one
Authors: Franklin Ronald B. , McMurtry Randolph J. , Nelson Sidney D.
Published: October 2006

A method has been described for the synthesis of tritiated [7‐3H]‐3β,16β‐dihydroxy‐5‐androsten‐17‐one of high specific activity starting from [7‐3H]‐5‐androsten‐17‐one. The identity of the radioactive steroid was established by thin layer chromato‐graphy, gas chromatography and gas chromatography combined with mass spectroscopy. The radiolabelled steroid may be used to study its disposition and metabolism in experimental animals and also to further investigate the potential role of 3β,16β‐dihydroxy‐5‐androsten‐17‐one in patients with low renin essential hypertension.
Synthesis of 4‐|2‐(dimethylamino) ethyl‐2‐14C| phenol (hordenine‐α‐14C)
Authors: Russo C. A. , Gros E. G.
Published: October 2006

4‐|2‐(Dimethylamino)ethyl‐2‐14C| phenol (hordenine‐α‐14C) has been synthesised in three steps from |14C|potassium cyanide and p‐benzyloxybenzyl chloride which in turn was obtained in four steps from p‐hydroxybenzoic acid.
Preparation of ω‐123I‐labelled fatty acids by 123I‐for‐Br exchange: Comparison of three methods
Authors: Laufer Peter , MacHulla Hans‐Jürgen , Michael Helmut , Coenen Heinz Hubert , El‐Wetery Afaf Sayed , Kloster Gerd , Stöcklin Gerhard
Published: October 2006

Long chain ω‐123‐I‐labelled fatty acids such as 16‐I‐hexadecanoic‐, 17‐I‐heptadecanoic‐, and 16‐I‐hexadec‐9‐enoic acid have been prepared without adding carrier by nucleophilic 123I‐for‐Br exchange in acetone, in the melt, and by use of phase transfer catalysts in non‐polar solvents. While preparation in refluxing acetone required reaction times of more than 2 hours to reach saturation yields, halogen exchange in molten bromofatty acids at temperatures of about 150 °C gave rise to yields of about 80% of radiochemically pure 17‐123I‐heptadecanoic acid within only 5 minutes. Comparable yields were also obtained using Kryptofix 221 in refluxing toluene after 10 minutes.
Synthesis of carbon‐14 and deuterium labeled N‐nitroso‐2(3′,7′‐dimethyl‐2′,6′‐octadienyl)aminoethanols
Authors: Abidi S. L. , Fish U. S. , Service Wildlife , Idelson A. L.
Published: October 2006

Methods of preparation of carbon‐14 and deuterium labeled N‐nitroso‐2(3′,7′‐dimethyl‐2′,6′‐octadienyl)aminoethanols are described. The primary synthetic method involved alkylation of ethanolamine or ethylglycine with suitable chlorides and subsequent mild nitrosation. Isomeric 14C‐nitrosamines were also prepared by selective α‐cleavage of the di‐substituted ethanolamine with nitrous acid.
Synthesis and biodistribution of acetyl‐3,5‐br‐82‐dibromosalicylic acid
Authors: Wong Steven H. , Spencer Richard P.
Published: October 2006

Acetyl‐3,5‐Br‐82‐dibromosalicylic acid (dibromoaspirin) was synthesized by radiobromination of salicylic acid to yield 3,5‐dibromosalicylic acid, followed by acetylation of this intermediate. Biodistribution studies in mice with and without a neuroblastoma showed that the tumor/blood radioactivity ratio was low (0.3 at one hour). Thin layer chromatography of urine indicated that only 20 to 30% of the radioactivity corresponded to dibromoaspirin. Studies of rabbits with inflammatory lesions showed that the inflammatory/normal tissue uptake ratio was 1.0 to 1.9. The RBC/plasma ratio was less than 0.5. Low uptake of radioactivity was likely due to rapid dehalogenation in vivo.
Synthesis of 125I‐labeled 14‐iodo‐9‐tetradecynoic acid
Authors: Otto C. A. , Brown L. E. , Wieland D. M. , Beierwaltes W. H.
Published: October 2006

The synthesis and radioiodide exchange labelling of 14‐iodo‐9‐tetradecynoic acid (1), a potential suicide inhibitor of acyl‐CoA dehydrogenase or enoyl‐CoA isomerase, is presented. Tissue distribution data in dogs are reported.
The preparation of tritium labeled methadone and its metabolites
Authors: Seltzman Herbert H. , Wyrick Steven D. , Pitt Colin G.
Published: October 2006

The synthesis and catalytic tritium reduction of 1,2‐dehydro analogs of (‐)‐methadol, (‐)‐α‐acetylmethadol, and (‐)‐α‐acetyl‐N‐normethadol afforded the labeled compounds with high specific activity (44‐60 Ci/ mmole). The use of the homogeneous catalyst (ϕ3P)3RhCl resulted in specific introduction of tritium without scrambling. (+)‐Methadone‐1‐3H (25 Ci/mmole) was obtained by oxidation of (‐)‐methadol‐1,2‐3H2 followed by sodium hydroxide exchange of the 2‐3H.
Synthesis of deuterium‐labeled 7‐azanorobrnane and 2‐azabicyclo [2.2.2]‐octane derivatives
Authors: Marchand Alan P. , Allen Robert W.
Published: October 2006

The syntheses of four specifically‐deuterated 2,3‐benzo‐7‐azanorbornane derivatives and three specifically‐deuterated 5,6‐benzo‐2‐azabicyclo[2.2.2]octane derivatives are described.
Synthesis of 14C‐labeled indole‐3‐acetylaspartic acid
Authors: Cohen Jerry D.
Published: October 2006

The synthesis of indole‐3‐acetyl‐2‐14C‐N‐aspartic acid from carrier‐free indole‐3‐acetic acid‐2‐14C (54.5 mCi/mmole) and bis‐t‐butyl‐l‐aspartic acid was accomplished by coupling with dicyclohexylcarbodiimide followed by removal of the ester blocking groups by treatment with 2 N NaOH.
Synthesis of carbon‐14 labelled antimicrobial agents. II. Synthesis of apalcillin‐14C sodium
Authors: Yoshitake Akira , Kamada Takeshi , Gomi Hideyuki , Nakatsuka Iwao
Published: October 2006

Sodium 6‐[ (R)‐2‐(4‐hydroxy‐1,5‐naphthyridine‐4‐14C‐3‐carboxy‐14C‐amido)‐2‐phenylacetamido]penicillanate (apalcillin‐14C sodium) (1) was synthesized for use in metabolic studies. Reaction of ethyl malonate‐1‐14C (2) with ethyl orthoformate in the presence of zinc chloride gave ethyl ethoxymethylenemalonatel‐14C (3), which was condensed with 3‐aminopyridine to give the aminopyridylacrylate‐14C (4). Cyclization of 4 in boiling. Dowtherm A followed by hydrolysis of the resulting ester gave 4‐hydroxy‐1, 5‐naphthyridine‐4‐14C‐3‐carboxylic‐14C acid (5). Condensation of 5 with 6‐[ (R)‐2‐amino‐2‐phenylacetamido]penicillanic acid by the activated ester method yielded apalcillin‐14C triethylamonium (7), which in turn was treated with sodium 2‐ethylhexanoate, giving apalcillin‐14C sodium (1) in the overall yield of 17% based on 2.
A convenient synthesis of nitrogen‐15 and deuterium labelled octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX)
Authors: Coburn M. D. , Ott D. G.
Published: October 2006

The preparation of pure octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX) labelled with nitrogen‐15 and deuterium was accomplished by sequential nitrolysis of appropriately labelled octahydro‐1,5‐diacetyl‐3,7‐endomethylene‐1,3,5,7‐tetrazocine. The latter compounds were obtained from the reaction of acetic anhydride with hexamethylenetetramine that was specifically labelled by the reaction of the appropriate formaldehyde and ammonia.
Inhibitors of sterol synthesis. Synthesis of [2,4‐3H]5α‐cholest‐8(14)‐ene‐3β,7α,15α‐triol and [2,4‐3H]5α‐cholest‐8(14)‐en‐38‐ol‐15‐one
Authors: Parish Edward J. , Schroepfer George J.
Published: October 2006

Oxidation of 5α‐cholest‐8(14)‐ene‐3β,7α,15α‐triol with silver carbonate‐celite gave 5α‐cholest‐8(14)‐ene‐7α,15α‐diol‐3‐one in 88% yield. Treatment of the latter compound with tritiated water under basic conditions gave a labeled product which was reduced with lithium tri‐tert‐butoxyaluminum hydride in tetrahydrofuran to give [2,4–H]5α‐cholest‐8(14)‐ene‐3β,7α,15α‐triol which was obtained in high purity after medium pressure liquid chromatography in the form of its triacetate derivative. Treatment of the labeled triol with concentrated hydrochloric acid in 95% ethanol gave the desired [2,4‐3H]5α‐cholest‐8(14)‐en‐3β‐ol‐15‐one.
Separation of inorganic iodide in the analysis of some iodoorganic radiopharmaceuticals
Authors: Lucka Barbara , Siuda Andrzej
Published: October 2006

A paper chromatography technique using 33% w/v aqueous solution of ammonium sulphate as a solvent has been applied for fast separation of inorganic radioactive iodide from labelled organic compound in the analysis of some iodoorganic radiopharmaceuticals of common use.

L‐triiodothyronine, L‐thyroxine, Rose Bengal and bromosulphthalein are retained at the starting spot while iodide migrates at Rf 0.5. The separation is obtained at a development path of 5cm in about 10min.

Sodium o‐iodohippurate, however, migrated at Rf 0.4 and its separation from inorganic iodide was not achieved under the conditions employed.
Preparation of deuterium labelled α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)
Authors: Lauridsen Jørn , Honoré Tage
Published: October 2006

The preparation of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) with deuterium α to the carboxylic acid group (2) and in the exocyclic methyl group (5), respectively, are described. The deuterium labelled AMPA (2) was synthesized by hydrolysis and decarboxylation of the corresponding di‐ester (1), whereas the deuterium labelled AMPA (5) was prepared via a catalytic deuteration of the bromoderivative (3).
Preparation of deuterium labelled catecholamines
Authors: Saraswat Lakshmi D. , Kenny Janis M. , Davis Sharon K. , Justice Joseph B.
Published: October 2006

The preparation of deuterium labelled catecholamines and their metabolites is described. The procedures involve simple treatment of the compounds in DC1/D2O solution. Mass spectra of these labelled compounds — as their PFP or TFA derivative — are presented. The relative intensity of ions suitable for selective ion monitoring are given for each compound. Results are presented concerning ease or difficulty of deuteration. The compounds studied include dopamine, tyramine, 3‐methoxytyramine, norepinephrine, metanephrine, normetanephrine, homovanillic acid and dihydroxyphenylacetic acid.
Synthesis of acetylene‐19C2
Authors: Hsu Daniel K. , Freeberg Michael D. , Duerst Richard W.
Published: October 2006

The preparation of acetylene‐13C2 from calcium and amorphous carbon‐13 by way of the intermediate calcium carbide‐13C2 is described.
The synthesis of [ring‐U‐14C] DDD from [ring‐U‐14C] DDT using rat liver homogenate
Authors: Fawcett S. C. , King L. J. , Stanley P. I. , Bunyan P. J.
Published: October 2006

1,1‐Di[ring‐U‐14C] (4‐chlorophenyl)‐2,2‐dichloroethane ([14C] DDD) was prepared by the anaerobic incubation of 1,1‐di[ring‐U‐14C] (4‐chlorophenyl)‐2,2,2‐trichloroethane ([14C] DDT) with homogenised rat liver in buffer. This gave a good yield of DDD which was purified chromatographically. The overall recovery of 99.5% pure DDD was 68%.
A rapid synthesis of A‐ring bromine‐77‐labelled estrogens with high specific activity
Authors: Wilbur D. S. , Bentley G. E. , O'Brien H. A.
Published: October 2006

A rapid method of no‐carrier‐added radiobrominations of A‐ring estrogens has been demonstrated. The method employs N‐chlorosuccinimide and high specific activity sodium bromide‐77 to generate an electrophilic brominating agent, which when reacted with phenolic steroids, yields three primary products. Two of the radiobrominated products have been shown to be the phenolic ortho brominated regioisomers, and the third product is believed to be a reaction intermediate. The use of HPLC afforded a method of separation and isolation of radiobrominated products. The 2‐bromo‐77Br‐ and 4‐bromo‐77Br‐ isomers were found to be quite stable in vitro, where‐as the suspected intermediates were not. A specific activity range of 600‐1200 Ci/mmole and radiochemical yields of 25‐30% were obtained for the 4‐bromo‐77Br regioisomers.
An improved synthesis of labelled dibromochloropropane
Authors: Buchman O. , Azran J. , Pri‐Bar I. , Shimoni M.
Published: October 2006

A continuous three‐step micro‐synthesis of 1,2‐dibromo‐3‐chloropropane, labelled with tritium in position 1 and 2, is described. A specific activity of 10.8 Ci/mmol is obtained. The yield observed in the uninterrupted overall synthesis is appreciably lower than that in the controlled step‐by‐step synthesis.
Labelling of fluorinated aromatics by isotopic exchange with [18F]fluoride
Authors: Cacace Fulvio , Speranza Maurizio , Wolf Alfred P. , Fowler Joanna S.
Published: October 2006

The efficient and rapid nucleophilic exchange of fluorine by fluoride‐18F ion in aromatic rings is reported here utilizing rubidium‐18F‐fluoride in DMSO on model compounds. Specific activities in the 3 × 104 Ci/mol region are readily achievable. Nucleophilic substitution is shown to be an attractive modality for fluorine‐18 labeling of aromatic compounds.
Synthesis of tritium labelled precocenes
Authors: Banerji A. , Goomer N. C.
Published: October 2006

Regiospecific syntheses of tritium labelled precocene I (5a) and precocene II (5b), the antijuvenile hormones, have been accomplished. The syntheses involved condensations between 2‐hydroxyacetophenones (1) with acetone‐T to give cross condensation products 2 which on cyclodehydration furnished 2,2‐dimethyl‐4‐chromanones‐(2‐gem dimethyl‐T) (3). Reduction of 3 with lithium aluminium hydride gave chroman‐4‐ols (2‐gem dimethyl‐T) (4). Dehydration of 4 furnished 2,2‐dimethyl‐ chromenes‐ (2‐gem dimethyl‐T) (5). Starting with appropriate acetophenones and acetone‐T, precocene I (7‐methoxy‐2,2‐dimethylchromene) and precocene II (6, 7‐dimethoxy‐2, 2‐dimethylchromene) labelled with tritium in the 2‐gem dimethyl positions, have been synthesised in high chemical as well as radiochemical yields.
Small‐scale preparation of 14C2‐pentaerythritol
Authors: Susàn Alexander B. , Duncan William P.
Published: October 2006

14C2‐Pentaerythritol (14C‐PE) at approximately 8 mCi/mmole was prepared in 76% yield on a 3‐mmole scale via a base‐catalyzed condensation of acetaldehyde‐14C2 with 1.5% aqueous CH2O.
Reparation of 3H‐, and 14C‐labeled ethylmorphine
Authors: Yost Yul , Holtzman Jordan L.
Published: October 2006

7,8‐Didehydro‐4,5‐epoxy‐3‐ethoxy‐17‐methyl(3H)‐, and −17‐methyl (14C)morphinan‐6‐ol were prepared by substituting the N‐methyl group with/acarbphenoxy group which was then either reduced with LiAl3H4 or removed to remethylate the N‐atom with 14CH3I.
Synthesis and characterization of cis and trans‐4‐d−1‐1‐tetralol
Authors: Groenewold G. S. , Gross M. L.
Published: October 2006

Trans‐4‐d−1‐tetranydronaphthalen‐1‐ol (trans‐4‐d−1‐1‐ tetralol) was synthesized from 1,4‐epoxy‐1,2,3,4‐ tetrahydronaphthalene using lithium tri‐tert‐butoxyaluminodeuteride. Cis‐4‐d−1‐1‐tetralol was made by epimerizing the trans‐ compound. Both compounds were characterized by high field 360 MHz NMR spectroscopy.
Synthesis of tritium labelled catechol
Authors: Hwang K. K. , Bhooshan B. , Kouri R. E. , Henry C. J.
Published: October 2006

The preparation of tritium labelled catechol by catalytic reduction of tetrabromocatechol is described. Recrystallization of catechol (U‐3H) after silica gel column purification gave 68% yield of the desired product with 98% purity as assayed by high performance liquid chromatography.
Synthesis of the fungicide [14C]triadimefon
Authors: Rouchaud Jean , Meyer Joseph
Published: October 2006

The synthesis of the fungicide [14C]triadimefon is described. Bromine transformed pinacolone into α ‐bromopinacolone; this reacted with 4‐chloro‐[U‐14C] phenol yielding 1‐(4‐chloro [U‐14C]phenoxy)‐3,3‐dimethyl‐2‐butanone; this was transformed by bromine into 1‐(4‐chloro[U‐14C]phenoxy)‐1‐bromo‐3,3‐dimethyl‐2‐butanone; this last compound reacted with 1,2,4‐triazole to yield [14C]triadimefon, i.e., 1‐(4‐chloro [U‐14C] phenoxy)‐3,3‐dimethyl‐1‐(1H‐1,2,4‐triazol‐1‐yl)‐2‐butanone. [14C]Triadimefon, having the specific activity 0.88 mCi/mmol, was obtained in 58% overall yield from 4‐chloro[U‐14C]‐phenol.
Enzymatic synthesis of 5‐3H‐indole‐3‐acetic acid and 5‐3H‐indole‐3‐acetyl‐myo‐inositol from 5‐3H‐L‐tryptophan
Authors: Michalczuk Lech , Chisnell John R.
Published: October 2006

Labeled 1‐tryptophan is converted to indole‐3‐acetamide and then to indole‐3‐acetic acid by enzymes from Pseudomonas savastanoi. Labeled indole‐3‐acetic acid can be converted to indole‐3‐acetyl‐1‐0‐β‐D‐glucose and to indole‐3‐acetyl‐myo‐inositol by enzymes from kernels of Zea mays sweet corn.
Catalytic tritiation and 3H NMR spectroscopy of complex organic mixtures ‐ application to oil shale process waters
Authors: Farrier David S. , Jones John R. , Bloxsidge James P. , Carroll Leonor , Elvidge John A. , Saieed Mahmoud
Published: October 2006

Several catalytic tritium exchange procedures have been investigated in order to accomplish uniform and random incorporation of tritium into the diverse organic solutes present in an oil shale process water. Comparative proton and tritium nuclear magnetic resonance (NMR) spectroscopy revealed that a Raney nickel/THO system resulted in a reproducible procedure wherein the individual components are tritiated randomly in stable positions in proportion to their concentration. This approach to the labelling of complex organic mixtures opens new avenues for radiotracer studies in environmentally important areas.
Labelled compounds of potential biological interest VII. Synthesis of 3‐deoxy‐D‐manno‐[1‐14C]octulosonic acid (D‐manno‐KDO) of high specific activity
Authors: Bondesson Göran , Fagervall Ingrid , Gosztonyi Tamas , Jansson Anita , Ohlberger Annesophie , Ab Astra Läkemedel
Published: October 2006

The preparation of the title compound from 2‐deoxy‐D‐manno‐heptose with potassium [14C] cyanide followed by subsequent oxidation is reported. Frequent use of HPLC has made it possible to follow and optimize the different reaction steps. The synthesis was carried out on the millimole level and the product had a specific activity of 50 mCi/mmol.
Radiation stability of angiotensin II‐amide and of its tritiated derivatives
Authors: Kopoldová J. , Hrnčíř Š. , Mezö I.
Published: October 2006

The gamma‐radiolysis of aqueous solutions of the peptide hormone angiotensin II‐amide and the beta‐autoradiolysis of its tritiated preparations were studied. The radiation loss and the decrease of biological activity of angiotensin II‐amide was evaluated. The main fractions of radiation products were separated and compared with the products formed during the storage of tritiated angiotensin II‐amide. The principal radiation processes taking place during the irradiation of angiotensin II‐amide were discussed.
A synthesis of [14C] progabide®‐ a new anticonvulsant
Authors: Allen J. , Giffard D.
Published: October 2006

Progabide®, 4‐[[(4‐chlorophenyl) (5‐fluoro‐2‐hydroxyphenyl)‐methylene]amino] butanamide, labelled individually with carbon‐14 in the butanamide side‐chain and in the imino carbon were synthesised for pharmacokinetic and metabolism studies. The former from potassium [14C] cyanide and the latter from barium [14C] carbonate in overall radiochemical yields of 33.8 and 42.2 % respectively.
Synthesis of N,N‐dimethyl[2‐14C] morpholinium chloride
Authors: Adamus Jan , Paneth Piotr , Reimschűssel Władysław
Published: October 2006

N,N‐dimethyl [2‐14C] morpholinium chloride was obtained from [1‐14C] acetic acid in five‐step synthesis with [2‐14C] morpholine as the intermediate.
The transfer of radioactivity of HSA‐containing samples of 125I insulin preparations during their storage
Authors: Kopoldová J.
Published: October 2006

In 125I insulin preparations, preserved in the form of lyophilized solutions with human serum albumin, the transfer of radioactivity from the insulin molecules to the higher molecular weight fractions was observed. After one month storage this transfer corresponded to 7 % of the total radioactivity and it increased proportionally to the length of the storage of iodinated preparations under simultaneous decrease of their biological activity. The results obtained with stored 125I insulin preparations and these preparations irradiated with external gamma‐source were compared and discussed.
Synthesis of [2‐14C] 3′‐deoxythymidin‐2′ ‐ENE (d4T) and [5–125I] 3′ ‐azido‐2′, 3′‐dideoxy‐5‐iodouridine: Potent inhibitors of human immunodeficiency virus (HIV‐1)
Authors: Lin Tai‐Shun , Gao You‐Song , Michael August E. , Qian He‐Ying , Prusoff William H.
Published: October 2006

The syntheses of [2‐14C] 3′ ‐deoxythymidin‐2′ ‐ene (d4T) and [5‐125I] 3′ ‐azido‐2′, 3′ ‐dideoxy‐5‐iodouridine in a one‐pot operation are described.
Synthesis of deuterated arylalkanoic acids for use as internal standards in gas chromatography/mass spectrometry assays for non‐steroidal anti‐inflammatory drugs
Authors: Dawson M. , McGee C. M. , Smith M. D. , Vine J. H.
Published: October 2006

A general method for the deuteration and purification of undeactivated arylalkanoic acids commonly used as non‐steroidal anti‐inflammatory drugs is described.
The synthesis of org 3770 labelled with 3H, 13C AND 14C
Authors: Kaspersen Frans M. , Van Rooij Fons A. M. , Sperling Eric G. M. , Wieringa Joop H.
Published: October 2006

The syntheses of 1,2,3,4,10,14b‐hexahydro‐2‐methylpyrazino[2,1‐a]pyrido [2,3‐c][2]benzazepine (Org 3770) labelled with 3H (and 2H), 13C and 14C are described. Tritiated Org 3770 was prepared either by exchange under alkaline conditions with tritiated water or catalytic reductive dehalogenation of a chloro analogue with 3H2. 13C‐labelled material was obtained in a seven‐step synthesis starting from 13C‐labelled benzene whereas 14C‐Org 3770 was prepared in a three‐step synthesis starting with 14CO2. All labelled compounds were analyzed by TLC, HPLC, MS and NMR.
Synthesis of L‐[5‐11C]ornithine
Authors: Ding Yu‐Shin , Antoni Gunnar , Fowler Joanna S. , Wolf Alfred P. , Langstrom Bengt
Published: October 2006

No‐carrier‐added L‐[5‐11C]ornithine was synthesized in 25–40% radiochemical yield in a synthesis time of 50 min (EOB) and a specific activity >2.1 Ci/umol by the displacement reaction of potassium [11C]cyanide with the functionally protected y‐bromohomoserine followed by selective reduction of the [11C]nitrile with cobalt chloride‐sodium borohydride complex, deprotection with 6M HCl(aq), and purification by HPLC. During the course of these studies it was found that cyanide ion is generated from acetonitrile in the presence of potassium hydroxide and kryptofix 222.
An efficient, one‐pot synthesis of 2‐deoxy‐2‐[18F]fluoroacetamido‐D‐glucopyranose (N‐[18F]fluoroacetyl‐D‐glucosamine), potential diagnostic imaging agent
Authors: Tada Masao , Oikawa Atsushi , Iwata Ren , Fujiwara Takehiko , Kubota Kazuo , Matsuzawa Taiju , Sugiyama Hiroshi , Ido Tatsuo , Ishiwata Kiichi , Sato Tachio
Published: October 2006

A rapid, one‐pot synthesis of 2‐deoxy‐2‐[18F]fluoroacetamido‐D‐glucopyranose (N‐[18F]fluoroacetyl‐D‐glucosamine) (1) starting from [18F]fluoride and ethyl bromoacetate is described. The synthesis was accomplished by a combination of halogen exchange, alkaline hydrolysis, and condensation. [18F]Fluoride was produced by the 18O (p, n) 18F nuclear reaction using the cyclotron. The total synthesis time, the radiochemical yield, and purity of (1) are ca. 90 min, ca. 9.1%, and >98%, respectively. Sugar (1) showed the diagnostic tumor‐imaging activity.
Synthesis of 4‐o‐(4,6‐ethylidene‐α‐D‐glucopyranosyl)‐4′‐demethyl‐3′‐O‐[14C]methyl‐4‐epipodophyllotoxin
Authors: Swigor J. E. , Haynes U. J.
Published: October 2006

The synthesis of the title compound (5) is described. Treatment of 4‐O‐(4,6‐ethylidene‐α‐D‐glucopyranosyl)‐4′‐demethyl‐4‐epipodophyllotoxin with sodium metaperiodate in acetonitrile formed the highly colored 4‐O‐(4,6‐ethylidene‐α‐D‐glucopyranosyl)‐3′,4′‐dioxo‐4‐epipodophyllotoxin (1). Hydrogenation using 10% palladium on carbon produced the 3′,4′‐dihydroxy compound (2). Protection of the 4′ hydroxy was achieved by benzylation (3). Treatment with excess [14C]methyl iodide under basic conditions introduced the label on the 3′ position (4). Deprotection yielded the title compound in an overall yield of 6%.
Synthesis of mixtures of [2H6]myo‐inositol monophosphates suitable as internal standards for quantitative GC/MS and a simple synthesis of DL‐myo‐inositol‐1‐phosphate
Authors: Ghosh Suchitra , Sherman William R.
Published: October 2006

A mixture of DL‐[2H6]myo‐inositol‐1‐ and ‐4‐phosphate and (meso) myo‐inositol‐2‐ and ‐5‐phosphate is readily prepared on a 100 milligram scale from the mixed isomers of di‐O‐cyclohexylidene‐[2H6]myo‐inositol by phosphorylation with tetrabenzylpyrophosphate. The deblocked [2H6]myo‐inositol monophosphate isomers are obtained where the relative amounts of racemic myo‐inositol‐1‐phosphate ≥ ‐4‐phosphate ≥ ‐2‐phosphate ≥ ‐5‐phosphate. In addition a simple synthesis of DL‐myo‐inositol‐1‐phosphate was developed which was found to be unsatisfactory for the preparation of deuterium‐labeled product.
Synthesis of 13C and 2H‐labelled 2‐phenylcyclododecanones
Authors: Pushkara Rao V. , Wang Jin‐Feng , Turro Nicholas J. , Doubleday Charles
Published: October 2006

13C labelled (1,2 and 1,12) and perdeuterated derivatives of 2‐phenyl cyclododecanones, as precursors for labelled triplet flexible biradicals to probe magnetic isotope effects at the radical centers on the triplet decay dynamics, were synthesized. Isotopomers of 2‐phenylcyclododecanone‐13C2‐(1,2 and 1,12) were synthesized from cyclododecanone‐13C2‐(1,2) by dibromination, followed by phenylation with lithiumdiphenylcuprate. Cyclododecanone‐13C2‐(1,2) was obtained from 1, 10‐dibromodecane via the following sequence: (1) K13CN; (2) hydrolysis; (3) esterification; (4) acyloin condensation. Perdeuterio‐2‐phenyl cyclododecanone (95% isotopic purity) was prepared from unlabelled 2‐phenyl cyclododecanone by a substitution of deuterium for hydrogen by treatment with excess D2O, catalyzed with D2‐reduced PtO2 in the presence of D2O2.
Synthesis of stable isotope‐labelled analogs of the cysteine and N‐acetylcysteine conjugates of tetrachloroethylene
Authors: Bartels Michael J. , Miner Virginia W.
Published: October 2006

Stable isotope‐labelled analogs of the cysteine and N‐acetylcysteine conjugates of tetrachloroethylene have been prepared. S‐(1,2,2‐Trichlorovinyl)‐DL‐cysteine‐3,3‐2H2 was synthesized in a rapid, one‐step procedure from tetrachloroethylene and DL‐cysteine‐3,3‐2H2. Unlabelled S‐(1,2,2‐trichlorovinyl)‐L‐cysteine was prepared in a similar fashion. The corresponding 13C‐N‐acetyl‐S‐(1,2,2‐trichlorovinyl)cysteine compounds were then prepared via acetylation of the deuterated and unlabelled cysteine conjugates with 13C‐acetyl chloride.
Synthesis of deuterium labelled analogs of fluazifop and haloxyfop
Authors: Bartels Michael J. , Gatling Sterling C.
Published: October 2006

Synthetic routes have been described for the preparation of stable isotope‐labelled analogs of two aryloxyphenoxypropionates, each containing approximately four deuterium atoms in the central phenyl ring of the molecule. Fluazifop‐2′,3′,5′,6′‐2H4 [2‐(4‐((5‐(trifluoromethyl)‐2‐pyridinyl)‐oxy)phenoxy)propionic acid‐2′,3′,5′,6′‐2H4] and haloxyfop‐2′,3′,5′,6′‐2H4 [2‐(4‐((3‐chloro‐5‐(trifluoromethyl)‐2‐pyridinyl)oxy)phenoxy)propionic acid‐2′,3′,5′,6′‐2H4] were synthesized from the common intermediate HPPA‐2′,3′,5′,6′‐2H4 [2‐(4‐hydroxyphenoxy)propionic acid‐2′,3′,5′,6′‐2H4]. This intermediate was obtained from HPPA via acid‐catalyzed deuterium exchange (2H2SO4 in 2H2O and CH3O2H).
The synthesis of [2H], [3H], and [14C]‐labeled 8β‐[(methylthio)methyl]‐6‐propylergoline mesylate (pergolide mesylate), a potent, long‐acting dopamine agonist
Authors: Wheeler William J. , Kau Donald L. K. , Bach Nicholas J.
Published: October 2006

The [3H]‐ and two [14C]‐isotopomers of 8β‐[(methylthio)methyl]‐6‐propylergoline mesylate (pergolide mesylate) have been synthesized. The [3H]‐derivative was synthesized by the palladium catalyzed tritiation of the corresponding 6‐allyl derivative. Reaction of 8β‐[(methylthio)methyl]‐ergoline with 1‐[14C]‐1‐propyl bromide yielded pergolide labeled in the 6‐propyl group. Alternatively, reaction of 8β‐mesyloxy‐6‐propylergoline with [14C]‐sodium cyanide, followed by base hydrolysis, yielded 8β‐carboxy‐6‐propylergoline‐[14C], which was subsequently converted to pergolide mesylate radiolabeled in the 17‐position via a four step sequence.
Preparation of paraherquamide labeled with deuterium or tritium
Authors: Blizzard Timothy A. , Rosegay Avery , Mrozik Helmut , Fisher Michael H.
Published: October 2006

Deprotonation of paraherquamide (1a) at C‐24 and subsequent deuteration (or tritiation) is described. The procedure afforded 24‐2H‐paraherquamide (1b) with 66% deuterium incorporation at C‐24. Modification of the deuteration procedure to allow the introduction of tritium resulted in the preparation of 24‐3H‐paraherquamide (1c) with specific activity 3.7 Ci/mmol.
Fluorinated benzamide neuroleptics. 1. Radiosynthesis of (S)‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐(2[F‐18]fluoroethyl)‐2‐methoxybenzamide: A potential fluorine‐18 labeled PET radiotracer for dopamine D2 receptors
Authors: Mukherjee Jogeshwar , Perry Bruce D. , Cooper Malcolm
Published: October 2006

The synthesis of a tosylate precursor for the radiosynthesis of a potential PET radiotracer, (S)‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐(2‐[18F]fluoroethyl)‐2‐ methoxybenzamide is reported. Reaction of 18F‐fluoride with the tosylate provides the radiolabeled product in 10–25% yield. Specific activity of the radiotracer varied between 600–800 Ci/mmol after purification of the product mixture by reverse phase HPLC.
Structure biodistribution relationship of radioiodinated tropeines: Search for a molecular probe for the characterization of the cocaine receptor
Authors: Basmadjian Garo P. , Mills Stanley L. , Kanvinde Mangesh , Basmadjian Nareg P.
Published: October 2006

Three iodinated analogs of cocaine were synthesized and radiolabeled by isotope exchange in the presence of Cu++ using a “kit” procedure. 2′‐Iodococaine,2′‐iodotropacocaine and 2′‐iodobenzoyl tropine radiolabeled with 125I were injected in mice and their biodistribution studied. Activity with all three radiolabeled compounds peaked in the brain and heart between 5 and 30 min. post injection. Activity from 125I‐2′‐iodococaine (S.A.=468 mCi/mmol), peaked in the brain at 15 min (2.38% injected dose/g) and showed a plateau in the heart between 5 and 60 min post injection (1.67–2.16%). 125I‐2′‐iodotropacocaine (S.A.=407 mCi/mmol) at 5 min had the highest uptake in the brain (8.16%) and the heart (4.44%) while activity from 125I‐2′‐iodobenzoyl tropine (S.A.=407 mCi/mmol) peaked in the brain at 15 min (4.19%) and at 5 min in the heart (3.33%). The biodistribution of 125I‐2′‐iodococaine paralleled literature values obtained with 3H‐/14C‐cocaine. We conclude that radioiodinated tropeines radiolabeled with 123I may be developed into useful probes to examine and characterize the cocaine receptor in‐vivo by SPECT imaging.
Synthesis of [2‐14C]thymidine: A potential route for [2‐11C]thymidine
Authors: Vander Borght T. , Pauwels S. , Lambotte L. , De Saeger C. , Beckers C.
Published: October 2006

We report a three‐step synthesis of thymidine, starting from trace amounts of urea, that allows rapid introduction of radioactivity in C2‐position of the pyrimidine ring. Thymine was produced within 5 min with a 60% yield by cyclocondensation of urea and diethyl β‐methylmalate in fuming sulfuric acid (15% SO3). Thymidine was further synthesized by the enzymatic transfer of deoxyribose onto thymine with a 90% yield achieved within 10 min. Using [14C]urea as precursor, the present method allowed the synthesis of radiochemically pure [2‐14C]thymidine in 35 min with a cumulative yield of 40%.
Synthesis of [3H]win 35,065‐2; A new radioligand for cocaine receptors
Authors: Naseree T. M. , Abraham P. , Kepler J. A. , Carroll F. I. , Lewin A. H. , Kuhar M. J.
Published: October 2006

Treatment of methyl (‐)‐3β‐phenylnortropane‐2β‐carboxylate with [3H]CH3I afforded [3H]WIN 35,065‐2 with specific activity of 25 Ci/mmol, a new ligand for the cocaine recognition site.
Deuterium labelling of the antidepressant drug doxepin for disposition studies in human subjects
Authors: Prakash Chandra , Saleh Samir , Taber Douglass F. , Wilkinson Grant R. , Blair Ian A.
Published: October 2006

Two methods have been developed for the introduction of deuterium into the doxepin molecule. The key intermediate (6,11‐dihydro‐1,2,3,4‐2H4‐dibenz[b,e]oxepin‐11‐one, 5) was prepared by condensation of ethyl 2‐bromomethylbenzoate with [2H6]‐phenol, saponification of the resulting ester, and dehydration with trifluoroacetic anhydride. Using this key intermediate, E‐(1,2,3,4)‐2H4‐doxepin was prepared for administration to human subjects. (1,2,3,4)‐2H4‐N‐desmethyldoxepin, (1,2,3,4,1′,2′,2′)‐2H7‐doxepin, (1,2,3,4)‐2H4‐(N2H3)2‐doxepin (2H10‐doxepin) and (1,2,3,4,1′,2′,2′)‐2H7‐N‐desmethyldoxepin were also prepared for use as internal standards in GC/MS assays. The deuterated compounds contained less than 0.5% protium impurity.
Synthesis of 3‐[125I]‐iodo‐phencyclidine for biological studies
Authors: Ponchant M. , Dreux Y. , Kamenka J. M. , Chicheportiche R. , Beaucourt J. P.
Published: October 2006

After verification of the biological activity of 3‐iodo‐PCP by binding studies to the N‐methyl D‐aspartate gated channel, 3‐[125I]iodo‐PCP was prepared by reaction of sodium iodide with a triazene precursor. The radiochemical yield was optimized and after HPLC purification, 3‐[125I]iodo‐PCP was obtained with a high radiochemical purity.
Synthesis of tritiated diborane and cryptand [2.2.2]
Authors: Garmestani Kayhan , Link Jeanne M. , Krohn Kenneth A.
Published: October 2006

In order to provide a method for in vivo and in vitro detection of cryptand [2.2.2], tritiated cryptand was synthesized by reduction of appropriate bicyclic diamide with tritiated diborane. As part of this synthesis, tritiated diborane was synthesized by the reaction of tritiated sodium borohydride with boron trifluoride etherate and trapped in dry THF. This is a potentially useful agent for selective tritiation of molecules with functional groups which are prone to electrophilic attack.
Synthesis of high specific activity tritium labelled 1S,2S‐(‐)‐trans‐2‐isothiocyanato‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl)‐cyclohexyl]benzeneacetamide, a specific irreversible ligand for kappa opioid receptors
Authors: De Costa Brian R. , Thurkauf Andew , Rothman Richard R. , Jacobson Arthur E. , Rice Kenner C.
Published: October 2006

Optically pure tritium labeled 1S,2S‐(‐)‐trans‐2‐isothiocyanato‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl)cyclohexyl]benzeneacetamide, an affinity ligand specific for the kappa opioid receptor was synthesized from optically pure 1S,2S‐(‐)‐trans‐2‐amino‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl)cyclohexyl]benzeneacetamide via the sequence of dibromination (57%) followed by catalytic tritiation of the dibromide. The resulting tritium labelled aniline (14% yield, specific activity 31.2 Ci/mmol) was transformed to the title compound in 13.3% yield and 99+% radiochemical purity by treatment with thiophosgene.
Regiospecific tritium labeling of aromatic acids, amides, amines and heterocyclics using homogeneous rhodium trichloride and ruthenium acetylacetonate catalysts
Authors: Hesk David , Jones John R. , Lockley William J. S.
Published: October 2006

Homogeneous rhodium trichloride has been found to promote ortho‐tritiation with high regioselectivity in a wide range of aromatic carboxylic acids, amides and aralkylamines. Less successful results were obtained using o‐chlorobenzoic and o‐anisic acids where some decomposition was seen, and in acids and amides of the phenolic type, where a degree of electrophilic exchange accompanies the ortho‐exchange. The same catalyst has also been used to regiospecifically label a number of heterocyclics. In the course of investigations with other metal complexes ruthenium acetylacetonate has been identified as an excellent promoter of ortho‐exchange in benzoic acids.
Synthesis of [14C]WIN 54954
Authors: Ellames George J. , Kunec Ellen K.
Published: October 2006

A synthetic procedure for producing 5‐[5‐[2,6‐dichloro‐4‐(4,5‐dihydro‐2‐oxazolyl)‐(U‐14C)‐phenoxy]pentyl]‐3‐methylisoxazole, [14C]WIN 54954 is described. The synthesis is achieved in seven steps with an overall radiochemical yield of 13.7%, using [U‐14C]phenol as a source of radiolabel.
Synthesis of carbon‐14 labeled LTD4 antagonist MK‐571
Authors: Dean Dennis C. , Melillo David G. , Ellsworth Robert L.
Published: October 2006

The synthesis of (E)‐5‐(3‐(2‐(7‐chloroquinolin‐2‐yl)ethenyl)‐ phenyl)‐[5‐14C]‐4,6‐dithianonane dicarboxylic acid N, N‐dimethylamide ([14C]MK‐571), a high‐affinity LTD4 antagonist, from sodium [14C]cyanide via a five step sequence is described. Condensation of 3‐[14C]cyanobenzaldehyde with 7‐chloroquinaldine followed by nitrile reduction provided the [14C]aldehyde 2. The pivotal formation of the penultimate unsymmetrical dithioacetal intermediate was accomplished in a selective manner from aldehyde 2 by way of an O‐trimethylsilyl hemiacetal intermediate. Subsequent ester hydrolysis afforded [14C]MK‐571 in 14% overall radiochemical yield.
Synthesis of tritium labelled choline analogs
Authors: Rajagopal Srinivasan , Diksic Mirko
Published: October 2006

The synthesis of choline analogs S(+) and R(‐) 2‐hydroxy, 1‐N, N,‐dimethyl, N‐[3H]‐methyl, propylammonium iodide, 3b, 3a; R(+) and S(‐) 1‐hydroxy, 2‐N, N‐dimethyl, N‐[3H]‐ methyl, propylammonium iodide, 6b, 6a; and N, N‐dimethyl, N‐[3H]‐ methyl, propynylammonium iodide, 8 labelled with [3H] at the N‐CH3 position was achieved with a radiochemical yield of 40% and specific activity of 9.3 Ci/mmol. The preparation of desmethyl compounds, enantiomeric and racemic 1,‐N, N‐dimethylamino 2‐propanol 2a, 2b, 2ab; enantiomeric and racemic 2,‐N, N‐dimethylamino 1‐propanol 5a, 5b, 5ab is also described.
Preparation of biologically active radioiodinated thymopentin
Authors: Venkat Krish , Tischio John , Crowther Jonathan , Audhya Tapan , Goldstein Gideon
Published: October 2006

Thymopentin (TP5, Arg‐Lys‐Asp‐Val‐Tyr), a synthetic pentapeptide corresponding to amino acids 32–36 of the thymic hormone thymopoietin, has the biological activity of the parent compound. The tyrosyl residue was iodinated using the chloramine‐T method and the reaction mixture separated by HPLC into peaks corresponding to free TP5, mono‐iodo TP5 and di‐iodo TP5, identified by mass spectrometry. Biological activity was retained in the iodinated peptides but, surprisingly, free TP5 had lost biological activity during the separation process. The biologically active monoiodinated TP5 had a specific activity of 28 μCi/μg and will be useful in studies of receptor binding.