Showing papers in "Journal of Labelled Compounds and Radiopharmaceuticals in 1978"
TL;DR: 14C- 2-deoxy-2-fluoro-D-glucose has been synthesized from 14C-3,4,6-tri-0-acetyl-D -glucal by fluorination with F2 and CF3OF to study of local cerebral glucose metabolism.
Abstract: A convenient method for the synthesis of 18F-2-deoxy-2-fluoro-D-glucose (4) and 18F-2-deoxy-2-fluoro-D-mannose (8) by the direct fluorination of 3,4,6-tri-0-acetyl-D-glucal with 18F-F2 is described. 14C-2-deoxy-2-fluoro-D-glucose has been synthesized from 14C-3,4,6-tri-0-acetyl-D-glucal (from D-[14c(U)]-glucose) by fluorination with F2 (Method 1) and CF3OF (Method 2). These labeled analogs of 2-deoxy-D-glucose were required for the study of local cerebral glucose metabolism.
407 citations
TL;DR: In this paper, the synthesis of crystalline potassium phosphate-18O4 (monobasic) of high (∼ 90%) isotopic purity starting with PCl5 and 99% water 18O was described.
Abstract: The synthesis of crystalline potassium phosphate-18O4 (monobasic) of high (∼ 90%) isotopic purity starting with PCl5 and 99% water-18O is described. The yield of the salt free from contamination by metaphosphates and pyrophosphate is 85%.
59 citations
TL;DR: The synthesis of mixed isomeric 14C-indoleacetyl-myo-inositols from carrier-free β[2-14C]-indoleacetic acid (57.2 mCi/mmole) via an imidazolide intermediate is described in this paper.
Abstract: Synthesis of the mixed isomeric 14C-indoleacetyl-myo-inositols from carrier-free β[2-14C]-indoleacetic acid (57.2 mCi/mmole) and inositol via an imidazolide intermediate is described. Radiological decomposition of the indolylic compounds was prevented by the use of a volatile thiol, dithioethane, and anthracene.
31 citations
TL;DR: In this article, a six-step synthesis of methyl cis-9-octadecenoate-d6 was described, which gave a 45-55% overall yield.
Abstract: A six-step synthesis is described which gives a 45–55% overall yield of methyl cis-9-octadecenoate-d6. All reactions except the last give over 90% yields. Incorporation of deuterium is simple, efficient, and produces isotope purities of over 84%. The 2-alkoxytetrahydropyran is a key intermediate in this reaction sequence. The discovery that this intermediate can be directly converted to the alkyl iodide in >90% yields resulted in a significant increase in overall yields and simplified the total synthesis. The general synthetic scheme can be used for preparation of most positional monoenoic fatty acid isomers by varying the chain length of the deutero alkyl iodide which is coupled to an appropriate aldehydic ester using the Wittig reaction.
31 citations
TL;DR: Seven deuterium labelled steroids were prepared in good yield using a synthetic strategy that embodies C7 functionalisation by Cr VI allylic oxidation followed by deoxygenation of the resulting ketone with aluminium chlorodeuteride.
Abstract: Seven deuterium labelled steroids were prepared in good yield. The synthetic strategy embodies C7 functionalisation by Cr VI allylic oxidation followed by deoxygenation of the resulting ketone with aluminium chlorodeuteride. Subsequent elaboration of the di-deuterated compounds using standard procedures allowed the preparation of biologically important steroids containing 96% deuterium at C7.
26 citations
TL;DR: A synthetic procedure for testosterone-19, 19, 19-d3 is described in this paper, where deuterium labeling of the C-19 position was achieved by the Grignard reaction of 17β-acetoxy-5α, 10α-epoxy-estrane-3-cycloethyleneketal with deuterIUM labeled methyl magnesium bromide (CD3MgBr).
Abstract: A synthetic procedure for testosterone-19, 19, 19-d3 is described. Deuterium labeling of the C-19 position was achieved by the Grignard reaction of 17β-acetoxy-5α, 10α-epoxy-estrane-3-cycloethyleneketal with deuterium labeled methyl magnesium bromide (CD3MgBr). The synthesis resulted in a product with 97.8% d3 isotopic purity, which is selectively deuterated at C-19 and chemically pure.
26 citations
TL;DR: In this paper, the Wittig reaction between hexyl-3,3,4,4-d4-triphenylphosphonium bromide (or iodide) and methyl 12-oxodecanoate was used to synthesize deuterated 12-octadecenoates.
Abstract: Four geometrically isomeric deuterated 12-octadecenoates and their triglycerides were synthesized for use in metabolism studies in humans. Methyl trans-12-octadecenoate-15,15,16,16-d4 (81.7% d4) and the corresponding cis isomer (88.9% d4) were obtained by the Wittig reaction between hexyl-3,3,4,4-d4-triphenylphosphonium bromide (or iodide) and methyl 12-oxododecanoate. The phosphonium salt was derived, in several steps, from 3-hexynol and the methyl 12-oxododecanoate from cyclododecene. Methyl cis-12-octadecenoate-9,10,15,15,16,16-d6 (79.9% d6) was obtained via the Wittig reaction between hexyl-d4-triphenylphosphonium bromide and methyl 12-oxododecanoate-9,10-d2. This deuterated aldehyde ester was prepared by lead tetraacetate oxidation of methyl 12,13-dihydroxyoctadecanoate-9,10-d2 which was obtained, in several steps, from Vernonia anthelmintica seed oil. A simple and convenient stereospecific synthesis of methyl trans-12-octadecenoate-9,10-d2 (84.9% d2) was accomplished by thermal decomposition of methyl 12,13-di-O-(ethoxymethylene)-octadecanoate-9,10-d2 which was prepared, in several steps, from 12,13-epoxy-9-octadecenoate obtained from Vernonia oil. All deuterations were catalyzed by tris(triphenylphosphine)chlororhodium. cis- and trans- isomers were separated on an Amberlyst XN 1005 column impregnated with silver ions.
24 citations
TL;DR: In this article, the authors showed that up to 95% chemical and radiochemical purity of carrier-free 5-iodo-2′-deoxyuridine-125I (or 131I) can be obtained by iodination of 2-DeoxyURidine at varying concentrations of radioactive NaI (1−10 mCi), as long as the molarity of deoxyurine in the reaction mixture is kept at or above 10−2 M.
Abstract: Consistently high yields (up to 95%) of carrier-free 5-iodo-2′-deoxyuridine-125I (or 131I) can be obtained by iodination of 2′-deoxyuridine at varying concentrations of radioactive NaI (1–10 mCi), as long as the molarity of deoxyuridine in the reaction mixture is kept at or above 10−2 M. At lower deoxyuridine molarities the reaction yield is significantly reduced. Several different purification procedures (Biogel P-2 400 mesh or Sephadex G-10 column chromatography, paper chromatography with water-saturated ethyl acetate or water-saturated butanol) are described. The two column chromatography systems yield iododeoxyuridine of > 95% chemical and radiochemical purity. The two paper chromatography systems are somewhat more involved, but yield 125I or 131I labeled 5-iodo-2′-deoxyuridine of > 99% chemical and radiochemical purity.
23 citations
TL;DR: Radiogenic oxygen-15 atoms generated in a cyclotron by the 14N(d, n)15O reaction are allowed to react directly with molecular hydrogen in the gas phase to produce labelled “carrier-free” H215O which can be used for biomedical purposes.
Abstract: Oxygen-15 labelled water has been prepared at high specific activities (> 100 mCi/ml) by nuclear recoil techniques available for use after 1 min from EOB. Radiogenic oxygen-15 atoms generated in a cyclotron by the 14N(d, n)15O reaction, are allowed to react directly with molecular hydrogen in the gas phase to produce labelled “carrier-free” H215O which can be used for biomedical purposes.
23 citations
TL;DR: Ausgehend von Benzol-14C via Nitrobenzene-14c and Anilin14C konnten mehrere markierte Umweltchemikalien dargestellt werden as mentioned in this paper.
Abstract: Ausgehend von Benzol-14C uber Nitrobenzol-14C und Anilin14C konnten mehrere markierte Umweltchemikalien darge-stellt werden. Durch Chlorierung von Anilin-14C bzw. dessen Acetylderivat wurden Chloraniline-14C erhalten. Gomberg-Bachmann bzw. Cadogan Reaktion diazotierter Chloraniline mit verschiedenen Chlorbenzolen fuhrte zu Di-, Tri- und Pentachlorbiphenylen-14C. Verkochung des Diazoniumsalzes von Anilin-14C ergab Phenol-14C, das zu 2,4,6-Trichlorphenol-14C umgesetzt wurde. Hexachlorbenzol-14C und Pentachlornitro-benzol-14C wurden durch Chlorierung von Nitrobenzol-14C dargestellt. Chloralkylen 9-14C wurde durch Friedel-Crafts Alkylierung von 2,4′-Dichlorbiphenyl-14C mit 2-Chlorpropan erhalten.
Upon the reaction of benzene-14C via nitrobenzene-14C and aniline-14C, some 14C-labelled environmental contaminants were synthesized. By chlorination of aniline-14C and acetanilide-14C we prepared chloroanilines-14C. Gomberg-Bachmann or Cadogan reaction of diazotated chloroanilines-14C with different chlorobenzenes gave di-, tri- and penta-chlorobiphenyls-14C. By boiling anilinediazonium sulfate-14C we prepared phenol-14C, which was chlorinated to give 2,4,6-trichlorophenol-14C. Hexachlorobenzene-14C and penta-chloronitrobenzene-14C were prepared by chlorination of nitrobenzene-14C. Chloralkylene 9-14C was synthesized by Friedel-Crafts alkylation of 2,4′ -dichlorobiphenyl-14C with 2-chloropropane.
21 citations
TL;DR: In this article, the preparation of deuterium labelled catecholamines and tryptophan metabolites using simple exchange reactions in DC1/D20 solution or reductions with Li Al D4 were used.
Abstract: The preparation of some deuterium labelled catecholamines, catecholamine metabolites and tryptophan metabolites is described. Simple exchange reactions in DC1/D20 solution or reductions with Li Al D4 were used. The deuterium labelled compounds prepared are suitable for use as internal standards for quantitative mass-fragmentographic analysis of their unlabelled analogs in biological material. Mass spectra of trimethylsilyl and trimethylsilyl-N-trifluoroacetyl derivatives of 2,5,6-trideutero vanillactic acid, 1,1-dideutero-1-hydroxy-2 (2,5,6-trideutero catechol)-ethane, 2,5,6-trideutero epinephrine, 2,5,6-trideutero normetanephrine and hexadeutero indole-3-acetic acid are given together with those of their natural occurring analogs.
TL;DR: In this article, the first conversion of L-tyrosine to p-hydroxyphenylpyruvic acid is described, which then is allowed to react with hydroxylamine to form p-Hydroxypheny lpyromvic acid oxime.
Abstract: Chemical syntheses of [UL- 14C]-labelled N-hydroxytyrosine, p-hydroxyphenylpyruvic acid oxime, p-hydroxyphenylacetaldoxime, and p-hydroxyphenylacetonitrile in high yields from L-[UL-14 C]-tyrosine are described. These syntheses involve initial conversion of L-tyrosine to p-hydroxyphenylpyruvic acid, which then is allowed to react with hydroxylamine to form p-hydroxypheny lpyruvic acid oxime. N-Hydroxytyrosine is obtained from the latter by reduction with sodium cyanoborohydride, and is oxidatively decar-boxylated to p-hydroxyphenylacetaldoxime by treatment with ammonia. Finally, p-hydroxyphenylacetonitrile is obtained by dehydration of the aldoxime with thionylchloride. All synthesized compounds were identified by combined GLC/MS of their trimethylsilyl derivatives. The commercial availability of several specifically labelled 14C, 2H, and 3H tyrosines and of 2H and 3H sodium cyanoborohydride makes the method equally useful for synthesis of various specifically labelled compounds.
TL;DR: N-Nitrosobis(2-hydroxypropyl)amine (BHP), a potent pancreatic carcinogen in the Syrian golden hamster, was synthesized with the 14C-label in the 1-position of one of the propyl groups using a four-step reaction sequence.
Abstract: N-Nitrosobis(2-hydroxypropyl)amine (BHP), a potent pancreatic carcinogen in the Syrian golden hamster, was synthesized with the 14C-label in the 1-position of one of the propyl groups Starting with lactic-1-14C acid, BHP was prepared utilizing a four-step reaction sequence, with an overall yield of 45% Intermediate purification was not necessary
TL;DR: In this article, the synthesis of deuterium labelled unsaturated, isomeric fatty acids was required for a series of triple-label feeding experiments, and the syntheses utilized tris (triphenylphosphine) - chlororhodium(I) catalyst for the incorporation of Deuterium.
Abstract: The synthesis of deuterium labelled, unsaturated, isomeric fatty acids was required for a series of triple-labelled feeding experiments. The preparation of the cis and trans isomers of methyl 8-octadecenoate-17, 18-d2, methyl 8-octadecenoate-13, 13, 14, 14-d4, methyl 13-octadecenoate-17, 18-d2 and methyl 13-octadecenoate-17, 17, 18, 18-d4 is described. The syntheses utilize tris (triphenylphosphine) - chlororhodium(I) catalyst for the incorporation of deuterium. The double bond is introduced by coupling a deuterated alkyl triphenylphosphonium salt with the appropriate aldehydic ester using the Wittig reaction. Optimization of conditions has increased the overall yields for these syntheses to ∼50% and the isotopic purity to >95%.
TL;DR: In this article, a one step synthesis of 15N-1 nicotinamide from the reaction of 15n ammonia with 1-N-(2,4-dinitrobenzene)-3-carbamoyl-pyridinium chloride was reported.
Abstract: A one step, high yield synthesis is reported of 15N-1 nicotinamide from the reaction of 15N ammonia with 1-N-(2,4-dinitrobenzene)-3-carbamoyl-pyridinium chloride. This reaction represents a specific example of a general and facile method for the synthesis of a wide variety of 15N labeled pyridine heterocycles.
TL;DR: The carbon-14 labelled steroids were synthesized from dihydrotestosterone-4-14C for use in studies of steroid metabolism.
Abstract: The carbon-14 labelled steroids, androsterone-4-14C, isoandrosterone-4-14C, 5α-androstanedione-4-14C, 5α-androstane-3β, 17β-diol-4-14C, and 5α-androstane-3α, 17β-diol-4-14C were synthesized from dihydrotestosterone-4-14C for use in studies of steroid metabolism.
TL;DR: In this paper, Wittig synthesis of 11-bromoundecanoic acid and 7-chloro-3-heptyne was used to synthesize hexadeuterated acids.
Abstract: Methyl esters of 11-octadecenoic-15, 16-d2, −15, 15, 16, 16-d4, and −10, 10, 15, 15, 16, 16-d6 acids were prepared by Wittig synthesis from intermediates derived from 11-bromoundecanoic acid and 7-chloro-3-heptyne. The dideuterated acid was prepared by partial hydrogenation of the heptyne followed by saturation with deuterium to 1-chloroheptane-4, 5-d2 for Wittig synthesis. Saturation of the heptyne with deuterium provided the Wittig intermediate for tetradeuterated acids. The hexadeuterated acids were prepared from tetradeuterated alkyl halide and 10-formyldecanoate-10, 10-d2.
TL;DR: In this paper, labelled 5-alkyluracils were obtained by condensation of the diethylacetals of α-formyl-carbonic acid esters with 14C-thiourea.
Abstract: 2-14C Labelled 5-alkyluracils were prepared by condensation of the diethylacetals of α-formyl-carbonic acid esters with 14C-thiourea. Compounds labelled at 4-C were synthesized by condensation of the labelled carboxylic acid derivatives with thiourea.
β-Anomers of 5-alkyl-2′-deoxyuridines were obtained in a fairly good radiochemical yield. Alkyl substituents ranged from methyl to tetradecyl, isopropyl and tertbutyl.
TL;DR: In this paper, activated palladium was used as catalyst for the hydrogen-tritium exchange in tricyclic antidepressants and specific activities obtained were: desipramine: 44.9 Ci/mmol; imipramines: 14.9 CI/mmoline; notriptyline: 2.0 Ci/moline; and amitriptymine: 1.7 Ci/nmoline.
Abstract: Activated palladium is used as catalyst for the hydrogen-tritium exchange in tricyclic antidepressants. The specific activities obtained are: desipramine: 44.9 Ci/mmol; imipramine: 14.9 Ci/mmol; notriptyline: 2.0 Ci/mmol and amitriptyline: 1.7 Ci/mmol.
TL;DR: A 10 to 300 fold increase in specific activity has been realized in the microwave discharge activation (MDA) of tritium gas labeling of a variety of compounds, up to the Ci/mmol range by the use of a cellulose Millipore filter as the labeling surface.
Abstract: A 10 to 300 fold increase in specific activity has been realized in the microwave discharge activation (MDA) of tritium gas labeling of a variety of compounds, up to the Ci/mmol range by the use of a cellulose Millipore filter (CMF) as the labeling surface. New reaction systems have also been developed to accommodate these and other large samples as well as multiple samples.
TL;DR: In this paper, a potent antiparasitic agent 3-nitro-6-propoxyimidazo[1, 2-b]-pyridazine (3) was synthesized, labeled with carbon-14 in the propoxy side chain, from n-propanol-1-14C and 6-chloro-3-nitrogenimidazoid]-1-b]pyridine (6, 2b) for absorption and metabolism studies.
Abstract: A potent antiparasitic agent 3-nitro-6-propoxyimidazo[1, 2-b]-pyridazine (3) was synthesized, labeled with carbon-14 in the propoxy side chain, from n-propanol-1-14C and 6-chloro-3-nitroimidazo-[1, 2-b]pyridazine (2). The final product was obtained in 58% radiochemical yield with specific activity of 1.13 mCi/mmole and radiochemical purity of greater than 99%. The deuterium labeled compound (4) was also synthesized for absorption and metabolism studies.
TL;DR: Results indicate that only those IDA derivatives in which the in vivo nitrogen has a pKa of approximately 6 show a high degree of radiochemical purity when radiolabeled using stannous ion as the reducing agent.
Abstract: Prerequisite to the development of technetium-99m containing drug and biochemical analogs is the ability to synthesize radiochemically pure technetium chelates from mixtures of an appropriate chelating agent, pertechnetate, and various reducing agents. This paper reports the synthesis of a series of N-substituted iminodiacetates (IDA) in which the pKa of the imino nitrogen was varied from 5.0 to 8.7. The chelating agents were labeled with Tc-99m using the stannous reduction method at aqueous pH's of 4.0, 5.5 and 8.0 and in absolute methanol. The radiochemical purity of each chelate was examined by high pressure liquid chromatography, paper electrophoresis, paper chroma-tography, and tissue distribution studies. Aqueous radiolabeling conditions resulted in pure technetium chelates only when the pKa of the imino nitrogen was approximately 6. Methanolic labeling conditions resulted in pure radiochemicals for all N-substituted imino-diacetic acids provided the imino nitrogen had a pKa of greater than 6. Under non-aqueous conditions, however, the radiochemical purity deteriorated with time for all compounds in which the pKa of the imino nitrogen was greater than 7. These results indicate that only those IDA derivatives in which the in vivo nitrogen has a pKa of approximately 6 show a high degree of radiochemical purity when radiolabeled using stannous ion as the reducing agent.
TL;DR: In this article, the compositions of different compounds of 99Tc(IV) and hydroxy-ethylidendiphosphonic acid have been evaluated using spectrophotometrical and potentiometric methods.
Abstract: The compositions of different compounds of 99Tc(IV) and hydroxy-ethylidendiphosphonic acid have been evaluated using spectrophotometrical and potentiometric methods. The ligand reacts with K2TcBr6 as well as with TcO4′ and SnCl2 under formation of Tc(OH)3LH3, Tc(OH)3LH2−, TcOOHLH2−, Tc2(OH)4LH33+ Tc2(OH)6LH2, Tc2(OH)8L4− and Tc(OH)x(LHy)2(4-x+8+2y)+ complexes respectively. In account of the minor technetium concentrations in 99mTc-radiopharmaceuticals for skeletal imaging the last mentioned compound may be the major component in such preparations.
TL;DR: During the metabolic activation and binding of the tritiated N-acetyl-2-aminofluorene to rat liver DNA in vivo, no tritium exchange occurred and incorporation into the ortho position is very low.
Abstract: 2-Aminofluorene, 4-amino-3-methylbiphenyl, 4-amino-biphenyl and 4-amino-4′-fluorobiphenyl were tritiated by acid catalyzed exchange of the corresponding nitro compounds followed by catalytic reduction. The exchange reactions were carried out by heating the nitro compounds in [3H]-trifluoroacetic acid with a catalytic amount of trifluoromethanesulphonic acid (TFMS). No loss of tritium could be detected during the conversion of the tritiated nitro compounds into the corresponding amines by catalytic hydrogenation. Incorporation into the ortho position is very low (< 4%). During the metabolic activation and binding of the tritiated N-acetyl-2-aminofluorene to rat liver DNA in vivo, no tritium exchange occurred.
TL;DR: A method is described for the tritium labelling of angiotensin II in two different positions and high specific radioactivity has been prepared starting from Dbt4-angiotens in II and Cpa8-angiotsin II.
Abstract: A method is described for the tritium labelling of angiotensin II in two different positions. /Tyr-3H/4-angiotensin II and /Phe-3H/8-angiotensin II of high specific radioactivity have been prepared starting from Dbt4-angiotensin II and Cpa8-angiotensin II, respectively.
TL;DR: Methylation with unlabelled sodium borohydride showed that up to seven amino groups can be methylated without loss of sweet-ness intensity in Thaumatin I.
Abstract: Thaumatin I has been labelled by reductive methylation of four of the e-amino groups of the lysine residues in the protein with tritiated sodium borohydride. Methylation with unlabelled sodium borohydride showed that up to seven amino groups can be methylated without loss of sweet-ness intensity.
The yield of the tritium-labelled methylated Thaumatin I was 31% with a tritium incorporation of 4.7%. Its specific radioactivity was 12.8 Ci/mmol.
TL;DR: In this article, the carcinogenic compounds 5-methylchrysene-5-14C, 2-methylaniline-methyl-14c and 3-methyl 2-naphthyl-amine-methyl 14C were synthesized using 14CO2.
Abstract: Procedures were developed for synthesis of the carcinogenic compounds 5-methylchrysene-5-14C, 2-methylaniline-methyl-14C and 3-methyl-2-naphthyl-amine-methyl-14C. In each case, label was introduced with 14CO2 and yields were acceptable for preparation of these compounds for metabolic studies.
TL;DR: In this article, the strict regiospecificity of the labeling in monotritiated glucoses, available commercially as aqueous solutions, is demonstrated by 3H n. m. r. spectroscopy.
Abstract: The strict regiospecificity of the labelling in some monotritiated glucoses, available commercially as aqueous solutions, is demonstrated by 3H n. m. r. spectroscopy. After storage there may however sometimes be label also present in the water or as non-glucose impurity. Internally referenced chemical shifts for D-glucopyranose in dilute solution in D2O at 25°C are provided for the first time.
TL;DR: Furan-2-[14C] carboxylic acid has been prepared in 74% yield by carbonation of 2-furyl-lithium as discussed by the authors, and it was isolated as the diacetate after catalytic reduction of the corresponding acid chloride.
Abstract: Furan-2-[14C] carboxylic acid has been prepared in 74% yield by carbonation of 2-furyl-lithium. Furan-2-[14C] aldehyde was isolated as the diacetate after catalytic reduction of the corresponding acid chloride. Nitration gave 5-nitrofuran-2-[14C] aldehyde diacetate and after hydrolysis to the aldehyde was condensed with 4-hydroxybenzhydrazide to give 5-nitrofuran-2-[14C]-aldehyde 4′-hydroxybenzoylhydrazone, [14C]-nifuroxazide, in an overall radiochemical yield of 15% from barium [14C]-carbonate.