bluuebunny/crossref_metadata_2025 huggingface dataset:
Syntheses with stable isotopes: Benzidine‐15N2
Authors: Whaley Thomas W.
Published: October 2006

Benzidine‐15N2 was prepared from 4,4′‐biphenyldicarboxamide‐15N2 by the Hofmann amide degradation. The diamide, in turn, was obtained from 4,4′‐biphenyldicarbonyl chloride and ammonium‐15N sulfate. An overall yield of 30–35% was obtained for the two steps. An attempted synthesis of N‐hydroxybenzidine is also described.
High specific activity labelling of some tricyclic antidepressants
Authors: Buchman O. , Pri‐Bar I.
Published: October 2006

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.
Effect of reaction temperature on enzyme conversion of pyrimidine bases to nucleosides and 2′‐ deoxynucleosides
Authors: Filip J. , Přitasil L. , Nejedlý Z. , Veselý J. , Čihák A.
Published: October 2006

Conversions of uracil to uridine and of uracil and thymine to the corresponding 2′‐deoxyribonucleosides catalyzed by the cell‐free extract of Escherichia coli B take place both at 37°C and 2°C. The yield of nucleosides formed during the short‐term incubation was higher at 37°C while during long‐term incubation it was higher at 2°C with the implication that the degradation of ribose‐ and 2′‐deoxyribose‐1‐phosphates in reaction mixtures kept at lower temperature is less considerable. The amount of 2′‐deoxyribonucleosides formed at 2°C was higher than that of ribonucleosides.
The synthesis of 14C‐labelled N‐aminooxyacetyl‐N′‐isonicotinoyl‐hydrazine dihydrobromide
Authors: Koltai E. , Bánfi D. , Kisfaludy L. , Dancsi L.
Published: October 2006

The N‐aminooxyacetyl‐N′‐isonicotinoylohydrazine dihydrobromide was labelled with 14C in two different positions. In one case we applied a new synthesis route via 14C labelled 4‐cyanopyridine and isonicotinic acid. In the other case aminooxyacetic acid was labelled in its carboxyle group.
A novel method for the preparation of highly tritiated methyl iodide, and its use for the syntheses of methyl‐3H‐labelled diazepam and the methiodides of (+)‐ and (−)‐bicuculline
Authors: Schwob R. , Wuersch J.
Published: October 2006

The syntheses of methyl‐3H‐labelled diazepam (4) and the methiodides of (+)‐ and (−)‐bicuculline (5) labelled with tritium in their methyl groups are described. Also reported here is a novel method for the preparation of triti‐ated methyl iodide (3) serving as the radioactive precursor for the substances mentioned above.
Synthesis of 14C‐labelled compounds of biological interest: 4‐methyl‐2‐pyridyl‐2‐furamide hydrochloride /MEPAF/
Authors: Ozdowska Zofia
Published: October 2006

A method of carbon‐14C introduction into the molecule of a new drug 4‐methyl‐2‐pyridyl‐2‐furamide hydrochloride /MEPAF/ has been elaborated and furan‐2‐14C‐carboxylic acid has been synthesized. Radioactivity distribution and chemical yields in this synthesis were established.
The synthesis and chemistry of [11‐14C]‐dibenz[b,f] [1,4]oxazepine
Authors: Harrison J. M. , Inch T. D. , Upshall D. G.
Published: October 2006

The synthesis of [11‐14C]‐dibenz[b,f][1,4]oxazepine 1 is described. Chromium trioxide – pyridine oxidation of 1 gives [11‐14C]‐10, 11‐dihydrodibenz [b,f][1,4] oxazepin‐11‐one 3 which on hydrolysis gives 2‐amino‐2′‐[14C]‐carboxydiphenylether 4. Hydrogenation of 1 affords [11‐14C]‐10, 11‐dihydrodibenz[b,f][1,4]oxazepine 5. The enzymic conversion of 1 into 2‐amino‐2′‐[14C]‐hydroxymethyldiphenyl ether 6 is described.
Synthesis of 1,2‐benzenedicarboxaldehyde‐d6 through the ozonization of naphthalene‐d8
Authors: Kwant B. H.
Published: October 2006

Naphthalene‐d was ozonized and the perdeuteroozonide was directly converted to 1,2‐benzenedicarboxaldehyde‐d by using dimethylsulfide. The perdeuteroozonide was also converted to 1,2‐benzenedicarboxaldehyde‐d6 through a three step synthesis, with the following intermediates: 2‐formylbenzoic acid‐d6, 2‐formylbenzoic acid‐d5 methylester and 1,2‐bis(hydroxymethyl‐d2) benzene‐d4. Both synthetic methods were described in detail.
A novel synthesis of maleic anhydride‐1‐ and ‐2‐13C and its subsequent conversion to labeled maleic hydrazide
Authors: Patterson John M. , Braun Loren L. , Haidar Nabeel F. , Huang Jack C. , Smith Walter T.
Published: October 2006

Maleic anhydride‐1‐ and 2‐13C were synthesized respectively from the available aspartic acid‐4‐ and ‐3‐13C by way of the corresponding bromosuccinic acids and their anhydrides. The maleic anhydrides were converted into 1,2‐dihydro‐3,6‐pyrida‐zinedione‐3‐ and ‐4‐13C on treatment with aqueous hydrazine sulfate. Nitrogen‐15 labeled 1,2‐dihydro‐3,6‐pyridazinedione was obtained from the latter reaction using hydrazine‐15N sulfate.
Synthesis of β‐alanyl‐arginyl‐glycyl‐phenylalanyl‐phenyl‐alanyl‐typosine amide labelled with tritium or carbon‐14
Authors: Hayashi Nobuyoshi , Kawakami Takeo , Shinozaki Kazuo , Wakimasu Mitsuhiro , Fujino Masahiko
Published: October 2006

The synthesis of β‐Ala‐Arg‐Gly‐Phe‐Phe‐Tyr‐NH2 labelled with tritium on the tyrosine residue or with carbon‐14 on the arginine residue is described. The tritium labelled compound VII was prepared in 49% radiochemical yield from L‐[3, 5‐3H] tyrosine and benzyloxycarbonyl‐β‐alanyl‐nitro‐arginyl‐glycyl‐phenylalanyl‐phenylalanine. The carbon‐14 labelled compound XVI was synthesized in 17% radiochemical yield from L‐[U‐14C]arginine and glycyl‐phenylalanyl‐phenylalanyl‐tyrosine amide.
Stereospecific synthesis of Δ24‐sterols labelled on the 26‐ or 27‐methyl group
Authors: Nicotra F. , Ronchetti F. , Russo G.
Published: October 2006

A convenient synthesis of Δ24‐sterols labelled on the 26‐ or 27‐methyl group, exemplified by the synthesis of [26‐3H]‐lanosterol, is described. Oxidation of lanosteryl acetate with SeO2 gives 3β‐acetoxylanosta‐8, 24‐dien‐26‐al; this is reduced to the corresponding labelled alcohol with KB3H4 and the obtained hydroxymethyl group is reduced to methyl group by hydrogenolysis of its sulfate monoester. 26‐Hydroxylanosterol can be transformed into 27‐hydroxy lanosterol by E→Z olefin inversion, so allowing the synthesis of lanosterol stereospecifically labelled at C‐27. Desmosteryl acetate analogously affords the corresponding 26‐aldehyde, which is easily reduced to the 26‐alcohol.

3H‐stereospecific synthesis.
Synthese De La Norfenfluramine 14C
Authors: Ronco G. , Renault H. , Rapin J. R. , Compagnon P.
Published: October 2006

The synthesis of 14C Norfenfluramine is described. The starting materials 14C‐Trifluoromethylbenzoic acid and 14C bistrifluoromethyl‐3‐benzophenone were prepared by carbonation of appropriate Grignard reagents. The labelled benzophenone was oxidized in high yield to give 14C‐trifluoromethylbenzoic acid. This 14C carboxylic compound was transformed into aldehyde which was condensed with nitroethane to form 14C‐trifluoromethyl‐3‐phenyl‐1‐nitro‐2‐propene,1–9. The latter compound was reduced with lithium aluminium hydride to give 14C‐norfenfluramine. The overall yield was 45,5% at a specific activity of 1,65 mCi/mM.
Synthesis of d,l‐1‐13C‐methionine
Authors: Andresen B. D.
Published: October 2006

The stable, isotopically labelled amino acid d, 1‐113C‐methionine, was prepared synthetically from 90% K13CN and 3‐(methylthio‐propionaldehyde. Chromatographic, infrared and mass spectrometric properties are presented which aid in the identification of this compound in body fluids and tissues.
Chemical synthesis of labelled intermediates in cyanogenic glucoside biosynthesis
Authors: Møller Birger Lindberg
Published: October 2006

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.
Synthesis of deuterium‐labeled nitrosomethylethylamines
Authors: Mangino Mario M. , Lijinsky William , Singer George M.
Published: October 2006

Ethyl isocyanate, N‐methylacetamide, N‐methylacetamide‐d3, and N‐methylacetamide‐d6 were reduced with lithium aluminum deuteride and then nitrosated with sodium nitrite to yield, respectively, nitrosomethyl (‐d3) ethylamine, nitrosomethylethyl (α‐d2) amine, nitrosomethylethyl (‐d5) amine, and nitrosomethyl (‐d3) ethyl (d5) amine. The characterization of the compounds by mass spectrometry is described.
Fluorine‐18 labelling of ortho‐fluorohippuric acid by isotope exchange reaction
Authors: Ndiokwere Ch. L.
Published: October 2006

The 18F‐labelling of o‐fluorohippuric acid by isotope exchange reactions has been studied in several organic solvents under varying reaction conditions. The solvent mixture ethanol/water (1:1) was found suitable for the isotope exchange reaction: a 100 per cent isotope exchange was observed for this system after an exchange time of one and half hours. No isotope exchange was observed in the molten state of the exchanging species.
Preparation of 35S‐labelled l‐methionine and l‐cystine by biosynthesis
Authors: Albahari S. R. , Skakun‐Todorovi M. B.
Published: October 2006

The modified method for biosynthesis of L‐methionine‐35S and L‐cystine‐35S from baker's yeast (Saccharomyces cerevisiae) is described. The yeast was cultivated in a sulphur‐deplated medium containing carrier‐free Na235SO4, under air bubbling during 24 hours. Yeast proteins were hydrolyzed enzymatically into free amino acids, and L‐methionine‐35S and L‐cystine‐35S were isolated by ion‐exchange chromatography on a column. Radioactive yields for L‐methionine‐35S and L‐cystine‐35S were 30% and 10%, respectively. The obtained products have high specific activity, 1–10 Ci/mmol, and radiochemical purity better than 95%.
Preparation of 2,4‐diamino‐6‐(diallylamino)‐s‐triazine‐2,4‐14c and its hypotensive metabolite, 2,4‐diamino‐6‐(diallylamino)‐s‐triazine‐2,4‐14c 3‐oxide
Authors: Thomas Richard C.
Published: October 2006

2,4‐Diamino‐6‐(diallylamino)‐s‐triazine‐2,4‐14C was prepared from K14CN in a four step sequence of reactions. The product was obtained in 26% yield at a specific activity of 1.01 mCi per mM. This product was converted to the hypotensive agent, 2,4‐diamino‐6‐(diallylamino)‐s‐triazine‐2,4‐14C 3‐oxide in 37% yield by oxidation with m‐chloroperbenzoic acid.
Preparation of carbon‐14 labeled 2‐phenyl‐3‐[p‐(2‐diethylaminoethoxy) phenyl]‐6‐methoxyindene hydrochloride
Authors: Thomas Richard C. , Marlatt Paul E.
Published: October 2006

2‐Phenyl‐3‐[p‐(2‐diethylaminoethoxy)phenyl]‐6‐methoxyindene‐314C hydrochloride was prepared from phenylacetic acid‐1‐14C in a four step sequence of reactions. The final product was obtained in 12.5% yield at a specific activity of 0.79 mCi per mM.
Markierung von N‐(2‐Diäthylaminoäthyl)‐S,S‐Diphenylsulfoximin mit Kohlenstoff‐14 in der Seitenkette und den Phenylringen
Authors: Liedtke B. , Vollmer K.‐O.
Published: October 2006

Ausgehend von Bariumcarbonat‐C wurde N‐(2‐Diäthylaminoäthy1)‐S,S‐diphenyl‐sulfoximin in 8 Stufen in Position 1 der Seitenkette radioaktiv markiert (IA). Bezogen auf die Ausgangssubstanz betrug die radiochemische Ausbeute 44,6%.

Zur Markierung in den Phenylgruppen (IB) wurde Benzol‐ (U‐l4c) verwendet. Über Diphenylsulfoxid und das entsprechende Sulfoximin wurde IB mit einer Ausbeute von 30,4% erhalten.
Synthesis of deuterium‐labelled lithocholic acid
Authors: Baillie T. A. , Karls M. , Sjövall J.
Published: October 2006

A convenient synthesis is reported of lithocholic acid labelled in high isotopic purity with two atoms of deuterium at C‐11. Incorporation of deuterium is achieved by base‐catalyzed equilibration of a 12‐oxo bile acid in heavy water. The product is converted in situ into its tosylhydrazone derivative which is reduced with sodium borohydride to afford the labelled 12‐deoxy bile acid.
Synthese des tritiummarkierten eberpheromons [5α, 6α‐3H]‐5α‐androst‐16‐en‐3‐on
Authors: Wagner H. , Römer J.
Published: October 2006

The synthesis of [5α, 6α‐3H]‐5α‐androst‐16‐en‐3‐one, starting with the catalytic tritiation of 3β‐acetoxy‐androst‐5‐en‐17‐one, is described. The so‐called “boar taint ketone” was obtained with high specific activity (21 Ci/mmol) and radiochemical purity better than 98 %.
The synthesis of specifically deuterated N‐acetyl‐6‐hydroxy‐5‐methoxytryptamine (6‐hydroxymelatonin) for use as an internal standard in mass spectrometry
Authors: Shaw G. J.
Published: October 2006

Specifically deuterated N‐acetyl‐6‐hydroxy‐5‐methoxytryptamine has been synthesised. The mass spectra of the labeled and unlabeled analogs are reported.
Synthesis of 14C‐labelled compounds. III. Synthesis of N‐Nitroso‐O,N‐14C‐dimethyl‐hydroxylamine
Authors: Arjungi Kusum N. , Krüger Friedrich‐Wilhelm , Wiessler Manfred
Published: October 2006

C14‐labelled O,N‐dimethylhydroxyurethane is synthesized from C14‐labelled dimethylsulfate and N‐hydroxy‐urethane. It is further converted without purification into O,N‐14‐C‐dimethyl‐hydroxylammoniumchloride, which was then nitrosated with sodiumnitrite in acidic medium to give N‐Nitroso‐O,N‐14C‐dimethylhydroxylamine in 49% yield.
The syntheses of deuterium labelled tobacco alkaloids: Nicotine, nornicotine and cotinine
Authors: Nguyen Trong‐Lang , Castagnoli Neal
Published: October 2006

A variety of deuterium labelled tobacco alkaloids has been prepared for metabolic studies. Reduction of myosmine with sodium borodeuteride provided nornicotine‐2′‐d1. Myosmine also underwent smooth base catalyzed exchange with deuterium oxide to myosmine‐3′,3′‐d2 which could be reduced to nornicotine‐3′,3′‐d2 and nornicotine‐2′,3′,3′‐d3. Thus avenues to nicotine alkaloids labelled at C2′, and/or C3′, have been established. Conversion of nornicotine to N‐ethoxycarbonyl‐nornicotine followed by lithium aluminum deuteride reduction gave nicotine‐N‐methyl‐d3. Nicotine‐2′,5′,5′‐d3 was prepared by oxidation of nicotine‐2′‐d1 to cotinine‐5‐d1 followed by lithium aluminium deuteride reduction.
Synthesis of iodine‐131 labelled 6β‐iodomethyl‐19‐norcholest‐5(10)‐en‐3α‐ol and 19‐iodocholest‐5‐en‐3α‐ol
Authors: Komatsu, H. , Maeda M. , Morita H. , Shimoirisa H. , Kojima M.
Published: October 2006

6β‐Iodomethyl‐19‐norcholest‐5(10)‐en‐3α‐ol (VI) was synthesized by the homoallylic rearrangement of 19‐iodocholest‐5‐en‐3α‐ol (V), which was obtained by the hydrolysis of 19‐iodocholest‐5‐en‐3α‐ol acetate derived from the displacement of cholest‐5‐ene‐3α,19‐diol 3‐acetate 19‐toluene‐p‐sulfonate with sodium iodide in isopropanol.

The radioiodinated V and VI were prepared by isotope exchange with sodium iodide‐I‐131 in acetone.
Synthesis of cholesteryl esters of labelled fatty acids
Authors: Grover A. K. , Cushley R. J.
Published: October 2006

Cholesteryl esters of variously labelled fatty acids have been synthesized in high yield by 1,1′‐carbonyldiimidazole activation of the acyl group and reaction of the resulting acylimidazole derivative with cholesterol. The method has been used to synthesize cholesteryl esters on micro and semimicro scales. Syntheses of the following esters are reported: cholesteryl palmitate‐1‐14C, cholesteryl palmitate‐d31, cholesteryl palmitate‐2,2‐d2, cholesteryl palmitate‐d31, cholesteryl palmitate‐2,2‐d2, cholesteryl palmitate‐3,3,4,4,5,5,6,6,7,7,8,8,9,9,‐10,10,11,11,12,12,13,13,14,14,15,15,16,16,16‐d29, cholesteryl 5‐doxylpalmitate and cholesteryl 16‐doxylstearate.
Syntheses with stable isotopes: Thymine‐2,6‐13C2
Authors: Redwine Carolyn M. , Whaley Thomas W.
Published: October 2006

A three‐step synthesis of thymlne‐2,6‐13C2 from urea‐13C, sodium cyanide‐13C, and α‐bromopropionic acid is described. The last reaction involves hydrogenation of α‐cyano‐13C‐propionylurea‐13C in aqueous acetic acid and produces thymine‐2,6‐13C2 in 50–60% yield. The mechanism of this reaction is discussed.
Synthesis of [4‐14C]diosgenin
Authors: Ferdinandi E. S.
Published: October 2006

[4‐14C]‐(25R)‐Spirost‐5‐en‐3β‐ol(diosgenin)l, specific activity 3.77 ± 0.02 mCi/mmole, was synthesized in four stees from (25R)‐5‐hydroxyspirost‐5‐en‐3‐oic‐3,5‐lactone 4 and [14C] methyl magnesium iodide with an overall yield of 18%. The preparation of the starting lactone from diosgenin is also described.
Preparation of selectively deuterated salen ligands
Authors: Brown Dennis G. , Srivanavit Chit
Published: October 2006

A number of selectively deuterated derivatives of the common ligand N,N′‐ethylenebis(salicylidenimine), salen, have been prepared. The synthesis involves preparation of selectively deuterated salicylaldehydes. Procedures necessary to carry out these syntheses are described below.
Synthesis of 21‐diazoprogesterone‐6,7‐3H2
Authors: Chiu Wen‐Hsiung , Wolff Manfred E.
Published: October 2006

The preparation of 21‐diazoprogesterone‐6,7‐3H2 is described. Progesterone was dehydrogenated with chloranil to give Δ6‐dehydroprogesterone. Degradation of the pregnane side‐chain with sodium hypobromite gave the corresponding carboxylic acid. Catalytic reduction with carrier‐free tritium followed by treatment with oxalyl chloride and then diazomethane afforded 21‐diazoprOgesterone‐6,7‐3H2 with a specific activity of 42 Ci/mmol.
Labelling of neuroleptic butyrophenones. II. Synthesis of 2′amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromethylpfenyl)piperidino]butyrophenone‐(carbonyl‐14C)
Authors: Nakatsuka Iwao , Kawahara Kazuo , Kamada Takeshi , Yoshitake Akira
Published: October 2006

2′Amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromemethylphenyl)‐piperidino]butyrophenone (ID‐470B)(1), a novel neuroleptic agent, was labelled with carbon‐14 at the carbonyl position for use in metabolic studies. The synthesis was achieved according to the reaction scheme shown in Fig. 1. Cyclopropyl 2,4‐difluorophenyl ketone‐(carbonyl‐14C) (2a) was prepared from cyclopropane‐carboxylic‐14c acid by the Friedel‐Crafts reaction with m‐difluoro‐benzene. Ring‐opening of 2a with hydrogen chloride gave 4‐chloro‐2′,4′‐difluorobutyrophenone‐1‐14c (3a). After ketalization of 3a, the resulted ketal (4) was condensed with the piperidine (5) and subsequently hydrolyzed with hydrochloric acid to give 6. Benzylamination of 6. with benzylamine, followed by debenzylation by catalytic hydrogenolysis gave ID‐4708‐(carbonyl‐14C) (1). The overall radiochemical yield of 1 from barium carbonate‐14C was 13%.
Preparation of radiolabelled 3α‐hydroxy‐7‐keto‐5β‐cholanic acid and its glycine and taurine conjugates
Authors: Carlson Gerald L. , Fromm Hans
Published: October 2006

3α‐Hydroxy‐7‐keto‐5β‐cholanic acid has been prepared from cholic acid by a route which allowed introduction of 3H into positions 11 and 12 of the steroid C ring. Labelling with 14C was done by halodecarboxylation and resynthesis of the carboxyl function with 14C cyanide. The conjugates of both 3H‐ and 14C‐labelled compounds with glycine and taurine were prepared. 14C‐labelled compounds were prepared by degradation of the carboxyl‐containing side chain to the norchloride, which was used to prepare the homologous 14C‐containing nitrile. Hydrolysis afforded the acid in good yield. 3H was introduced into the C ring of the steroid nucleus by dehydration of 3α,12α‐dihydroxy‐7‐keto‐5β‐cholanic acid to the Δ11‐alkene which was catalytically tritiated. Physical and spectral data are presented to characterize the new compounds and TLC methods for purification are reported.
High yield sulfonation of [14COOH]‐litholcholic and [14COOH]‐taurolithocholic acids
Authors: Kelsey Morris I. , Molina Jorge E.
Published: October 2006

Sulfate esters of [14COOH]‐lithocholic and taurolithocholic acids have been prepared using a sulfur trioxide·pyridine complex as the sulfonating reagent. The utilization of liquid‐liquid extraction or reversed‐phase silica gel and Amberlite XAD‐2 chromatographic techniques gave pure sulfate esters which did not contain inorganic salt impurities. These methods offer a useful one‐step approach to the synthesis of sulfate esters at the milligram level using commercially‐available labeled precursors.
Synthesis of mevalonolactone‐2,3‐13C2
Authors: Degraw Joseph I. , Uemura Ieaki
Published: October 2006

The synthesis of mevalonolactone with 13C‐labels at positions 2 and 3 is reported. Hydrolysis of methyl 3‐hydroxy‐3‐methyl‐5,5‐dimethoxy‐valerate‐2,3‐13C2 to the aldehydo acid followed by reduction with sodium borohydride yielded the title compound. The material is useful as a substrate in biosynthetic studies using 13C‐NMR as an analytical tool.
Synthesis of ring 14C‐methyl labeled retinyl acetate
Authors: Colwell William T. , Soohoo Caroline , Degraw Joseph I.
Published: October 2006

A method for incorporation of a 14C‐label in the ring geminal methyl moiety of Vitamin A is described. The procedure involves mono methylation of 2,6‐dimethylcyclohexanone with 14C‐methyl iodide as catalyzed by potassium hydride to afford 2‐14C, 2,6‐trimethylcyclohexanone. Subsequent condensation with an 11‐carbon acetylenic side chain, followed by reduction, acetylation and dehydration yielded 14C‐retinyl acetate. Final purification was achieved by preparative thin layer chromatography.
Synthesis of biopterin‐8a‐13C
Authors: Degraw Joseph I. , Brown Vernon H. , Uemura Ieaki
Published: October 2006

The synthesis of biopterin labeled at the angular 8a position with 13C is described. Cyano‐13C‐acetic acid was converted in three steps to benzyl 2‐aminocyanoacetate. Condensation of the amino cyano ester with the monoxime of 5‐deoxyl‐L‐arabinosone by a modification of the literature method afforded 2‐amino‐3‐benzyloxycarbonyl‐5‐(L‐erythro‐1′, 2′‐dihydroxypropyl) pyrazine‐1‐oxide‐2‐13C. This intermediate was condensed with guanidine to give biopterin‐8‐oxide‐8a‐13C, which was reduced to afford biopterin‐8a‐13C.
Preparation of 3H‐labelled apomorphine, N‐n‐propylnorapomorphine, and O, O‐dipivaloylapomorphine
Authors: Soine William H. , Salgo Peter , Smith Robert V.
Published: October 2006

Apomorphine and N‐n‐propylnorapomorphine were tritiated using trifluoroacetic acid‐ tritiated water mixtures. This provides a route to the synthesis of tritiated O,O‐dipivaloylapomorphine. Deuterium exchange and NMR studies indicate that exchange only involves protons at the C‐8 and C‐9 positions.
Synthesis of high specific activity R‐and S‐ warfarin‐3H
Authors: Cook C. E. , Tallent C. Ray , Ballentine Noel H. , Taylor George F. , Kepler John A.
Published: October 2006

4‐Hydroxy‐3‐[3‐oxo‐1‐(3‐bromophenyl)butyl]‐2H‐1‐benzopyran‐2‐one (3′ ‐bromowarfarin) was synthesized and resolved into its enantiomers by formation of the d‐10‐camphorsulfonate diastereoisomers, which were separated by liquid chromatography and hydrolyzed. The pure enantiomers were reduced with tritium gas to yield R‐ and S‐4‐hydroxy‐3‐[3‐oxo‐1‐(phenyl‐3‐3H)butyl]‐2H‐l‐ benzopyran‐2‐one (R‐ and S‐warfarin‐3′‐3H) of specific activity 31.2 and 24.9 Ci/mmole, respectively. The compounds have been used to develop a stereoselective radioimmunoassay for warfarin enantiomers.
Synthesis of [2‐14C] theobromine
Authors: Frischknecht P. M. , Baumann T. W.
Published: October 2006

[2‐14C] theobromine was prepared by the methylation of commercially available [2‐14C] xanthine with dimethyl sulfate. The yield was 44.5 % of the initially applied radioactivity.
Tritiuh‐labelling in two phenylalanine residues of norleucine11‐substance P
Authors: Bienert M. , Klauschenz E. , Ehrlich A. , Katzwinkel S. , Niedrich H. , Tót G. , Teplán I.
Published: October 2006

Norleucine11‐substance P and 4‐chlorophenylalanine 7.8‐Norleucine11‐ substance P were synthesized by fragment condensation. Phe/3H/7.8‐norleu‐cine11 ‐substance P was obtained by catalytic tritiation of the precursor peptide with a specific radioactivity of 27 Ci/mmole and full biological activity.
Synthesis of lipoidal drugs: ‐ Glycerides of radiolabelled aspirin
Authors: Kumar R. , Billimoria J. D.
Published: October 2006

Triglycerides containing aspirin in place of one or more fatty acid residues have been synthesised. Glycerol, mono and di palmitic acid glycerides were acylated with the acid chloride of [ 14C‐carboxyl ]‐aspirin to give the corresponding tri‐, di and mono‐aspirin glycerides.
Tritium nuclear magnetic resonance spectroscopy part 12. Patterns of labelling in tritiated folic acid and methotrexate
Authors: Evans E. Anthony , Kiteher J. Philip , Warrell David C. , Elvidge John A. , Jones John R. , Lenk Robert
Published: October 2006

Labelling patterns in tritiated folic acid and methotrexate have been examined by tritium nuclear magnetic resonance spectrometry. The results indicate that oxidative degradation with permanganate can give a false tritium distribution.
The synthesis of estragole labelled with deuterium ln single positions of the allylic side chain. In single positions of the allylic side chain
Authors: Monti D. , Gramatica P. , Manitto P.
Published: October 2006

[γ‐2H2]Estragole was synthesized via vinylation of 4‐ methoxy‐ [methylene‐2H2]‐benzyl chloride; [β‐2H]estragole via reduction of 3‐(p‐anisyl)‐propyne with bis‐3‐methyl‐2‐butylborane (obtained from LiAl2H4, BF3 etherate and 2‐methyl‐2‐butene) [α‐2H]estragole via reduction of the tosylhydrazone of 4‐methoxy‐[formyl‐2H]‐cinnamaldehyde with NaBH3CN.
A method for the preparation of 14C‐labeled carboxylic acids. Synthesis of 6,11‐dihydro[b,e]thiepin‐11‐one‐3‐yl acetic 14C‐acid
Authors: Parnes Howard
Published: October 2006

An example of a potentially general method for the preparation of 14C‐carboxylic acids based on the carbonation of an α‐lithiated carboxylate is described. This procedure requires only the unlabeled analog of the desired 14C‐acid as the precursor. The possibility of carrying out the selective decarboxylation of a malonic acid derivative with loss of only the unlabeled carboxyl group is described.
Photosynthetic preparation of galactose‐13C6 and glycerol‐13C3 using a marine red alga
Authors: Kollman V. H. , Gregg C. T. , Whaley T. W. , London R. E. , Hanners J. L.
Published: October 2006

The photosynthetic preparation of D‐galactose‐13C6 and glycerol‐13C3 from Gigartina corymbifera is described. The red marine algae biosynthesize the galactoside 2‐hydroxy‐1‐(hydroxymethyl)ethyl α‐D‐galactopyranoside (galactosylglycerol) during photosynthesis. The galactoside was isolated from an alcohol extract by an acetylation procedure and hydrolyzed to D‐galactose and glycerol. The average enrichment of the isolated products was 55 mol % 13C while the actual enrichment of newly synthesized material, determined by 13C nmr, was 80 mol % 13C after a photosynthetic period of 48 hr during which 90 mol % 13CO2 was administered. Thirty percent of the administered carbon was recovered in the products. The distribution of 13C in the galactose and glycerol was shown to be uniform by 13C nmr.
Syntheses du Diiodo 125I Practolol : Un Nouveau β‐Bloquant Potentiel
Authors: Pilichowski Jean‐François , Godeneche Denise
Published: October 2006

La synthèse d'un dérivé du Practolol marqué par 125I est décrite. En vue d'études métaboliques et pharcocinétiques, nous avons préparé le di 125I practolol avec un rendement de 11 % et une activité spécifique de 5 mCi/mmole.
The synthesis of some tritiated 5‐substituted uracil derivatives
Authors: Barr P. J. , Jones A. S. , Walker R. T. , Bohá L.
Published: October 2006

The synthesis of 5‐[3H‐ethynyl]uracil and 5‐acetyl[6‐3H]uracil in good yield and of a medium specific activity ( > 40 mCi/mmol) is described. The compounds are necessary for following the incorporation of these and other derived 5‐substituted uracils into DNA and also for studying the metabolism and mode of action of their deoxynucleosides, some of which possess antiviral properties.
Rapid synthesis of isotopically labelled methanes
Authors: Alei Mohammed
Published: October 2006

The reaction between carbon monoxide and hydrogen to form water and methane proceeds quantitatively in a single pass through a supported Ni catalyst bed at 250 – 350°C in an atmospheric‐pressure flow system. The system described is capable of rapid, continuous production of isotopically labelled methanes.
Synthesis of carbon‐14 labeled 3‐phenylpropoxyguanidine cyclohexylsulfamate
Authors: Hsi Richard S. P.
Published: October 2006

This report describes the synthesis of carbon‐14 labeled 3‐phenylpropoxyguanidine cyclohexylsulfamate from barium [14C]‐carbonate. The product is labeled at the 3‐position of the propyl chain, adjacent to the phenyl ring.
Preparations of deuterium labelled guvacine and isoguvacine
Authors: Christensen Søren Brøgger , Krogsgaard‐Larsen Povl
Published: October 2006

The preparations of guvacine hydrochloride, in which a proton in position 2 (11) and protons in positions 2 and 5 (10) are selectively exchanged by deuterium, and of [2,6‐2H]isoguvacine hydrobromide (14a) are described. The deuterium labelled guvacine salts 10 and 11 were synthesized by triethylamine catalyzed exchange of hydrogen for deuterium in methyl N‐nitroso‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate (3) followed by denitrosation and hydrolysis. Treatment of N‐nitroso‐1,4,5,6‐tetrahydropyridine‐3‐carboxylic acid with methanolic thionyl chloride gave 3,4,5,6‐tetrahydropyridin‐3‐on ketoxime. Compound 14a was prepared by sodium borodeuteride reduction of 4‐ethoxycarbonyl‐1‐methylpyridinium iodide (12) followed by N‐demethylation and hydrolysis of the intermediate.
Synthese Du Tertiobutyl‐2 dinitro‐4,6 Phenol Noyau‐14C (U) (“Dinoterbe” Noyau‐14C)
Authors: Noel Jean‐Pierre , Pichat Louis , Benakis Achille
Published: October 2006

(U‐14C) Phenol and isobutene under pressure in presence of aluminium phenoxide gave in 60 % yield a mixture of (ring U‐14C) 2‐t‐butylphenol (50 %) and (ring U‐14C)‐2,6‐di‐t‐butylphenol (10 %) which were separated by column chromatography on silicagel. Each t‐butylphenol was nitrated under appropriate conditions to give an 35 % overall yield of (ring‐U‐14C)‐4,6‐dinitro‐2‐t‐butylphenol : specific activity : 27.4 mCi/mMol which was proved by TLC and HPLC to be 99 % radiochemically pure.
Specific tritiation onto C‐2 and C‐5 positions of histidine ‐ containing peptide. Application to thyroliberin
Authors: Levine‐Pinto H. , Pradelles P. , Morgat J. L. , Fromageot P.
Published: October 2006

Specific methods of tritium labelling onto C‐2 and (or) C‐5 positions of the imidazole ring were successfully applied to thyroliberin (TRF, L‐Glu‐L‐His‐L‐Pro‐NH2).

Diazocoupling by diazotized sulphanilic acid and iodination by iodine monochloride of the histidyl residue were chosen to prepare precursors and to quantify the distribution of tritium atoms which were introduced.

Catalytic hydrogenolysis in the presence of tritium gas of 5‐iodohistidine2 ‐ and 2(4‐sulfophenylazo)histidine2 ‐ derivatives allowed to label these positions with specific radioactivities of 30 Ci and 25 Ci/mmole respectively. For comparison thyroliberin tritiated by direct catalytic exchange is labelled essentially onto C‐2 with a specific radioactivity of 30 Ci/mmole.
Synthesis of (4‐hydroxy‐3‐methoxyphenyl)‐α, α, β, β‐tetradeutero ethylamine
Authors: Ehrhardt J. D.
Published: October 2006

A five step synthesis of α, α, β, β‐d4‐3 methoxytyramine is described with an overall yield of 45% starting from methyl 4‐benzyloxy‐3‐methoxy benzoate.
Synthesis of deuterated and tritiated apogossypol
Authors: Powers Larry J. , Dorsett Preston H.
Published: October 2006

Apogossypol with deuterium or tritium in the 8 and 8′ positions can be synthesized by the base catalyzed deformylation of gossypol. The position of the labeling is established by the pmr spectrum of the material derived from the reaction of deuterium oxide and sodium deuteroxide. The specific activity of the tritiated material prepared from tritium oxide and sodium hydroxide is 110m Ci/m Mole. The methods described are also useful for the synthesis and storage of small quantities of unlabeled apogossypol.
Synthesis and quality control of long‐chain 18F‐fatty acids
Authors: Knust Ernst Joachim , Schüller Manfred , Stöcklin Gerhard
Published: October 2006

Introduction of fluorine‐18 into various positions of long‐chain fatty acids is described. The potential heart and liver radiopharmaceuticals 16‐18F‐hexadecanoic acid, 17‐18F‐heptadecanoic acid, 2‐18F‐, and (9,10)‐18F‐stearic acid have been prepared by nucleophilic F‐for‐Br exchange in the melt of the corresponding bromofatty acid methylesters in acetamide, followed by alkaline or acid hydrolysis. In the case of 17‐18F‐hepta‐decanoic acid saturation yields of about 30% have been obtained at an optimum reaction temperature of 150 °C and about 1 mg of KF‐carrier.
Preparation of carbon‐14 labelled guazatine (1,17‐BIS‐ [14C]‐guanidino‐9‐azaheptadecane triacetate)
Authors: Hudson H. R. , Pianka M. , Powroznik L. , Lynch V. P.
Published: October 2006

1,17‐Bisguanidino‐9‐azaheptadecane triacetate(Guazatine)has been prepared with carbon‐14 labelling of the guanidine carbon atoms, by interaction of 1,17‐diamino‐9‐azaheptadecane with S‐methyl‐ 14C ‐isothiouronium sulphate. The initial product was purified by precipitation as the carbonate which was then dissolved in aqueous acetic acid to give a 6 % solution of the triacetate, with specific activity of 20.8 μCi mmol−l.
Radioactively labelled epoxides. Part III. Tritium labelled steroid 16α, 17α‐epoxides
Authors: Sparrow Alan J. , Bindel Ulla , Oesch Franz
Published: October 2006

Tritium labelled (17‐3H) 16α, 17α‐epoxy‐androst‐4‐en‐3‐one and 16α, 17α‐epoxy‐estra‐1,3,5(10)‐trien‐3‐ol have been prepared on a large scale (200‐300 mg amounts) with efficient (i.e. activity of product exactly predictable) introduction of label. The preparative method is very inexpensive, since the tritium derives from tritiated water, the steroid starting materials are readily available, and high yields are obtained in all steps.
The preparation of 5′‐iodo‐125I‐Δ8‐THC; a radioligand for the radioimmunoassay of cannabinoids
Authors: Pitt Colin G. , Seltzman Herbert H. , Setzer Susan R. , Williams David L.
Published: October 2006

Nucleophilic exchange of 5′‐iodo‐Δ8‐THC and sodium iodide‐125 afforded 5′‐iodo‐125I‐Δ8THC with a maximum specific activity of 42 Ci/mmole. The specific activity could be increased to at least 100 Ci/mmole by iodide‐125 displacement of the corresponding 5′‐tosylate. A hapten 5′‐carboxy‐14C‐Δ9‐THC, for use in conjunction with this radioligand, was synthesized from 5′‐bromo‐Δ8‐THC.
Preparation of [14C]Acetamidino‐insulin
Authors: Matsuo Mitsuyoshi , Yamauchi Hirose , Ooyama Toshiro , Orimo Hajime
Published: October 2006

[14C]Acetamidino‐insulin was synthesized by acetamidination of insulin with methyl [14C]acetimidate hydrochloride. The acetamidino‐insulin contains two main components, which can be separated by DEAE‐cellulose column chromatography. They correspond to glycineA‐1 ‐ PhenylalanineB‐1 ‐ Nε ‐ lysineB‐29 ‐ [14C]acetamidino‐insulin and glycineA‐1 ‐ Nε ‐ lysineB‐29 ‐ [14C]acetamidino‐insulin. These immunological and biological activity was compared with that of native insulin.
Synthesis of double 15N‐labeled nitramines: N‐nitropiperidine and N‐nitrodimethylamine
Authors: Bulusu S. , Autera J. , Axenrod T.
Published: October 2006

Double 15N‐labeled N‐nitropiperidine and N‐nitrodimethylamine have been conveniently prepared by oxidation of the corresponding nitrosamines. Dimethylamine‐15N was commercially available while the required piperidine‐15N was synthesized from cyclopentanone via the Schmidt ring‐expansion procedure using potassium azide‐1‐15N, followed by hydride reduction of the resulting 2‐piperidinone‐15N.
Radiolysis of 131I‐O‐iodohippurate: A kinetic study
Authors: Hotte C. E. , Ice R. D. , Flynn G. L.
Published: October 2006

Although radiolytic decomposition of several radiopharmaceuticals has exhibited apparent first‐order kinetics, the dependence of decomposition on drug concentration precludes a first‐order rate process. A kinetic study of the decomposition of 131I‐o‐iodohippurate in aqueous solution was carried out to accurately assess the dependence of radiopharmaceutical decomposition on absorbed radiation dose, initial radiopharmaceutical concentration and, in addition, on the concentration of added free radical inhibitors. The fraction of 131I‐o‐iodohippurate remaining, (A/Ao), was found to decrease exponentially with increased absorbed radiation dose. The radiolytic decomposition rate, however, exhibited a Langmiurian relationship with respect to the initial concentration of the radiopharmaceutical present (Ao) and the initial concentration of free‐radical inhibitor present (Io).magnified imagewas derived to characterize these dependencies and demonstrated good correlation with experimental results. This equation may be of value in assessing the radiolytic stability of other radiopharmaceuticals.
The synthesis of C‐2 isotopically labeled optically pure warfarin and phenprocoumon
Authors: Porter William R. , Kunze Kent , Valente Edward J. , Trager William F.
Published: October 2006

Optically pure isotopically labeled phenprocoumon was prepared from resolved phenprocoumon via ring opening and decarboxylation followed by recarboxylation with suitably labeled (13C, 14C) diethyl carbonate and ring closure. A similar procedure was followed for the preparation of optically pure isotopically labeled warfarin after protection of the side chain carbonyl group by formation of an ethylene dithioketal derivative. The protecting group was quantitatively removed after incorporation of label by treatment with mercuric acetate.
Synthesis of [2‐14C] tetramethyluric acids
Authors: Citroreksoko P. S. , Petermann J. , Wanner H. , Baumann T. W.
Published: October 2006

[2‐14C]1,3,7,9‐, 0(2),1,7,9‐ and 0(8),1,3,7‐Tetramethyluric acid were prepared by methylation of [2‐14C]uric acid with dimethyl sulfate at pH 9. The yield after repeated (3x) purification by TLC was 44.9%, 4.4% and 6.3% respectively.
A synthesis of DL‐erythro‐2‐(4‐benzylpiperidino)‐1‐(4‐hydroxyphenyl)‐[1‐14C]propan‐1‐OL L‐(+)‐tartrate
Authors: Allen J.
Published: October 2006

The preparation of DL‐erythro‐2‐(4‐benzylpiperidino)‐1‐(4‐hydroxy‐phenyl)‐[1‐14C]propan‐1‐ol L‐(+)‐tartrate, Ifenprodil tartrate (Vadilex ®) from barium [14C]carbonate is described. The product was obtained in 29.2 % radiochemical yield and at a specifie activity of 47.6 mCi/mmol. This was diluted to 2 and 1 mCi/mmol for metabolism and distribution studies in man. The radiochemical purity of the diluted product exceeded 99 %.
Synthesis of S‐benzyl‐DL‐[1‐13C]cysteine and its incorporation into oxytocin and [8‐arginlne]vasopressin and related compounds by total synthesis. Separation of diastekeoisomers by partition chromatography and HPLC
Authors: Hruby Victor J. , Viswanatha V. , Yang Young C. S.
Published: October 2006

S‐Benzyl‐DL‐[1‐13C]cysteine was prepared from Na13CN by a three step synthesis and converted to the t‐butyloxycarbonyl derivative which was suitable for use in peptide synthesis. This compound was incorporated into the 1 and 6 positions of a variety of oxytocin and [8‐arginine]vasopressin derivatives and analogues via total synthesis using the solid phase method. The compounds were separated and purified by partition chromatography on Sephadex and their purity was checked by high pressure liquid chromatography. The compounds synthesized include [1‐hemi‐[1‐13C]cystine]oxytocin, [1‐hemi‐D‐[1‐13C]‐cystine]oxytocin, [1‐hemi‐[1‐13C]cystine, 8‐arginine]vasopressin, [1‐hemi‐D[1‐13C]cystine, 8‐arginine]vasopressin, [6‐hemi‐[1‐13C]cystine]oxytocin, [6‐hemi‐D‐[1‐13C]cystine]oxytocin, [1‐hemi‐D‐[1‐13C]cystine, 3‐D‐leucine]‐oxytocin, and [1‐hemi‐[1‐13C]cystine, 3‐D‐leucine]oxytocin.
A simple, rapid procedure for the preparation of deuterium‐labelled testosterone
Authors: Gaskell Simon J. , Finlay Elizabeth M. H.
Published: October 2006

A simple and rapid procedure for the preparation of [16,16‐2H2]‐and [16,16,17‐2H3]testosterone of high isotopic purity is described. [16,16‐2H2]DehydrOepiandrosterone is obtained by base‐catalysed exchange; reduction of the 17‐keto group using lithium aluminium hydride or lithium aluminium deuteride is followed by selective enzymic oxidation of the 3β‐hydroxy function with concomitant Δ5 to Δ4 isomerisation. The incorporation of deuterium in intermediates and products is established by gas chromatographic‐mass spectrometrie analyses of parent compounds and alkylsilyl derivatives. Deuterium labels in the 16 and 17 positions of testosterone are shown to be non‐labile under strongly acidic and basic conditions.
Synthesis of clonidine and 1,3‐dimethylclonidine labelled at specific positions with deuterium and carbon‐13
Authors: Hughes Helen , Baillie Thomas A
Published: October 2006

The synthesis is reported of a number of analogues of clonidine and 1,3‐dimethylclonidine labelled specifically and in high isotopic purity with deuterium and carbon‐13. 2,6‐Dichloro[4‐2H1] aniline and 2,6‐dichloro‐[3,4,5‐2H3]Janiline were employed to prepare compounds substituted in the aromatic ring with one and three atoms of deuterium, respectively, while the use of appropriate derivatives of ethylenediamine led to products in which the imidazol idine ring was labelled with carbon‐13 or deuterium.
A new method for labelling 11β‐hydroxy steroids: Synthesis of 18‐2H‐corticosteroids
Authors: Green Michael J. , Shue Ho‐Jane , Bartner Peter , Morton James B. , Youngstrom Richard E. , Meinwald Jerrold
Published: October 2006

A new method for labelling 11β‐hydroxy steroids is described. The procedure involves specifically placing the label on the angular C13 methyl group via the photolysis of the 11β‐nitrite ester (Barton reaction) and reaction of the resulting C18 radical with PhS‐2H in situ. Incorporations of 2H were 30‐40% for 9α‐H, 12‐21% for 9α‐F and <5% for 9α‐Cl corticosteroids. The extent of labelling was measured by mass spectrometry and the position of labelling was confirmed as C18 for two compounds by dmr, cmr and pmr spectroscopy.
Synthesis of perdeuterio‐N‐(1‐oxyl‐2,2,6,6‐tetramethyl‐4‐piperidinyl)maleimide, a highly sensitive spin probe
Authors: Venkatarmu Sindhaghatta D. , Pearson Donald E. , Beth Albert H. , Perkins Ray C. , Park Charles R. , Park Jane H.
Published: October 2006

Perdeuterio‐N‐(1‐oxyl‐2,2,6,6‐tetramethyl‐4‐piperidinyl)‐maleimide has been prepared to improve sensitivity and resolution in its ESR spectrum. The synthesis involved modifications of procedures known for the corresponding protonated analog. Spectral data are presented for the product to establish isotopic purity. A five‐fold enhancement of the ESR signal for the title compound relative to the proton counterpart has been observed.
An improved synthesis of 5,5‐dideuterocyclophosphamide
Authors: Jarman M. , Taylor G. N.
Published: October 2006

A high yielding synthesis of 5,5‐dideuterocyclophosphamide is described which involves the base catalysed deuterium exchange of 3‐hydroxypropionitrile and subsequent medium pressure catalytic hydrogenation to yield 1‐amino‐2,2‐dideuteropropan‐3‐ol. This compound is condensed with N,N‐bis(2‐chloroethyl)‐phosphoramidic dichloride to yield pure 5,5‐dideuterocyclophosphamide which is readily isolated as a crystalline monohydrate.
Labelling of neuroleptic butyrophenones. III. Synthesis of 2′‐amino‐4′‐fluoro‐4‐[4‐hydroxy‐4‐(3‐trifluoromethylphenyl)piperidino‐2‐14C] ‐ butyrophenone
Authors: Nakatsuka Iwao , Kawahara Kazuo , Yoshitake Akira
Published: October 2006

2′‐Amino‐4′ ‐fluoro‐4‐(4‐hydroxy‐4‐) (3‐trifluoromethylphenyl) ‐ piperidino‐2‐14Cbutyrophenone [ID‐4708‐ (piperidine‐14C]), a neuroleptic agent, was synthesized for use in metabolic studies. The synthesis was achieved by the reaction scheme shown in Fig. 1. 1‐Benzyl‐4‐piperidone‐2‐14C was prepared by Mannich reaction of paraformaldehyde‐14C with ethyl acryloylacetate and benzylamine, followed by treatment with hydrochloric acid, in 65% yield. Grignard reaction of the product with 3‐trifluoromethylphenyl‐magnesium bromide followed by hydrogenolysis gave 4‐hydroxy‐4‐(3‐trifluoromethylphenyl)piperidine‐2‐14C (8), which was condensed with 3‐(6‐fluoro‐2‐methyl‐3‐indolyl) propionic acid to give the 3‐indolylpropionylpiperidine‐14C (10). Conversion of 10 by reduction, oxidation and then hydrolysis led to ID‐4708‐(piperidine‐14 C) (1) in the overall yield of 9.6% from paraformaldehyde‐14C.
Carbon‐14‐labeled 2,3,7,8‐ and 1,2,7,8‐tetrachlorodibenzofuran
Authors: Gray Allan P. , McClellan W. J. , Dipinto V. M.
Published: October 2006

Both 2,3,7,8‐ and 1,2,7,8‐ tetrachlorodibenzofuran ‐U14C, specific activity 57 mCi/mmol, have been obtained in low yield but at < 98% purity via Pschorr cyclization of o‐phenoxyaniline ‐U14C, chlorination of the resultant dibenzofuran and separation of the tetrachloro isomers by hplc. The lower yields obtained in the Pschorr cyclization of “hot” o‐phenoxyaniline in comparison with the “cold” material are postulated to result from enhanced homolytic relative to heterolytic cleavage of the “hot” diazonium ion leading to a “hot” free radical which polymerizes. The completely anomalous results observed in the attempted palladium acetate‐mediated cyclization of diphenyl ether‐ U14C are likewise interpreted in terms of the intervention of a “hot” free radical.
Preparation of uniformly 14C‐labeled and 13C‐enriched catechol and hydroquinone via phenol
Authors: Chew Edward H. , Heys J. Richard
Published: October 2006

Catechol‐U‐14C and hydroquinone‐U‐14C were prepared from phenol‐U‐14C by mononitration followed by chromatographic separation of o‐ and p‐nitrophenol‐U‐14C. The nitrophenols were separately hydrogenated, and the resulting aminophenols were converted by diazotization followed by hydrolysis to the title diols. Phenol‐U‐14C was synthesized efficiently from benzene by nitration, reduction, diazotization and hydrolysis. A similar series of reactions beginning with benzene‐U‐13C gave phenol, catechol and hydroquinone containing more than 88% total carbon‐13.
Direct isotope determination of drugs labeled with stable isotopes of hydrogen, carbon, and nitrogen by field desorption mass spectrometry
Authors: Bahr U. , Schulten H.‐R.
Published: October 2006

By recording the molecular ion group with repetitive magnetic scanning and accumulation of the mass spectra in a multichannel analyser field desorption mass spectrometry was used to determine the isotopic abundances of three widely used drugs in their unlabeled and stable‐isotope labeled forms. The label content and statistical distribution of 2H, 13C and 15N in analogs of an antitumor agent, cyclophosphamide and one of its metabolites 4‐ketocyclophosphamide and of two analgesics antipyrine and carbamazepine were investigated. Using nanogram amounts of sample the precision and accuracy of the measurements achieved were below ±1% on an absolute basis.
Synthesis of isotopically labelled salicylates
Authors: Hawkins D. R. , Pryor R. W.
Published: October 2006

[13C‐carboxyl]Salicylic acid has been prepared by carbonation of 2‐benzyloxybromobenzene followed by reductive debenzylation. Deuterium and tritium labelled salicylic acid and 2H2/13C‐salicylic acid were prepared by reduction of the 3,5‐dibromo derivatives using Raney Ni‐Al. Deuterium labelled salicylic acid containing up to four deuterium atoms was prepared by catalytic exchange with Raney Ni‐Al in 5% NaOD/D2O.