bluuebunny/crossref_metadata_2025 huggingface dataset:
Syntheses of radiolabelled forms of a novel histamine H1 antagonist (SK&F 93944)
Authors: Cashyap M M , Mitchell M B , Osborne D C , Saunders D
Published: October 2006

A novel histamine H1 antagonist SK&F 939441, 2‐[4‐(5‐bromo‐3‐methylpyrid‐2‐yl)butylamino]‐5‐(6‐methylpyrid‐3‐yl‐methyl)‐4(3H)‐pyrimidone, has been labelled with carbon‐14 in two different positions for use in metabolism and pharmacoinetic studies. The four stage synthesis of [pyrimidone‐2‐14C] SK&F 93944 (7) from barium [14C]cyanamide is described. The overall radiochemical yield was 38%. [butylamino‐4‐14C] SK&F 93944 (14) was synthesised in four steps from [14C]methyl iodide. The key steps in this synthesis were alkylation of 2‐lithio‐3‐methyl pyridine with [14C]methyl iodide and the bromination of 4‐(3‐methyl‐2‐pyridyl)[4‐14C]butylamine in a liquid sulphur trioxide/freon mixture. The overall radiochemical yield was 1.6% from [14C]methyl iodide.
Synthesis of [2‐14C]dezaguanine mesylate (6‐amino‐1,5‐dihydro‐4H‐imidazo[4,5‐c]pyridin‐4‐one‐6‐14C methanesulfonate), a new antitumor agent
Authors: Hartman Jon D. , Alks Vitauts , Huang C. C. , Cook P. Dan
Published: October 2006

Dezaguanine mesylate (CI‐908 mesylate, 3‐deazaguanine mesylate, 6‐amino‐1,5‐dihydro‐4H‐imidazo[4,5‐c]pyridin‐4‐one methanesulfonate, 7), a new antitumor agent, was labeled in‐the 2‐position by use of a new synthesis to 3‐deazaguanine. Thus, methyl 4‐(hydroxymethyl)‐1‐(triphenylmethyl‐1H‐imidazole‐5‐carboxylate (10) was converted with thionyl chloride to the corresponding chloromethyl‐derivative 11, which was treated with [14C]‐potassium cyanide to afford the labeled penultimate intermediate, methyl 5‐(cyanomethyl)‐1H‐imidazole‐4‐carboxylate (12). Ring closure of 12 with methanolic ammonia and subsequent salt formation provided [2‐14C]3‐deazaguanine mesylate (13).
Synthesis of 2 deuterium labelled analogs of veralipride
Authors: Staveris S. , Schmitt A. , Jamet G. , Kerr R R. , Ottman L. , Jung L. , Koffel J. C.
Published: October 2006

Veralipride was labelled with trideuteromethyl groups first in the o‐methoxy and later in both o‐and m‐methoxy positions respective to the benzamide functions. Hydroxylated benzaldehydes were the starting materials and (CD3)2SO4 the labelling substance. A known synthesis was followed for veralipride‐d3. This synthesis was extensively modified in the final steps for veralipride‐d6 by introducing an ester exchange reaction which increased the overall yield.
Tritium labelled (±)‐10‐[2‐(1‐methyl‐2‐piperidinyl)ethyl]‐2‐(methyl‐mercapto)‐[3‐3H(n)]phenothiazine (thioridazine)
Authors: Wyrick Steven D. , Mailman Richard B. , Niedzwiecki Diane M.
Published: October 2006

The antipsychotic drug, thioridazine, differs from more classical antipsychotic drugs with respect to both some atypical psychopharmacological characteristics and to the critical involvement of active metabolites in its pharmacology. Tritium labelled thioridazine has been prepared in our laboratory by palladium catalyzed reduction of an aryl brominated precursor using carrier free tritium gas in THF. The product is labelled in the 3‐position of the phenothiazine ring system and a specifie activity of 12 Ci/mmole was obtained.
Synthesis of 122I‐ and 125I‐labelled meta‐dimethoxy‐N,N‐dimethyliodophenylisopropylamines
Authors: Mathis Chester A. , Shulgin Alexander T. , Sargent Thornton
Published: October 2006

The syntheses of 122I‐ and 125I‐labelled 2,4‐dimethoxy‐N,N‐dimethyl‐5‐iodophenylisopropylamine, 3,5‐dimethoxy‐N,N‐dimethyl‐2‐iodophenylisopropylamine and 2,6‐dimethoxy‐N,N‐dimethyl‐3‐iodophenylisopropylamine are described. The speed (3 min, including purification) and yield (45‐85%) obtained in direct iodination procedures utilizing chloramine‐T have allowed the use of the short‐lived positron emitter 122I (t1/2 = 3.6 min) in brain blood flow imaging studies. The three appropriate precursors (the meta‐dimethoxy‐N,N‐dimethylphenylisopropylamines) were prepared from the corresponding phenyl acetone analogues by reductive amination employing dimethylamine and NaCNBH3. The ketones were obtained from the appropriate nitrostyrenes through reduction with elemental Fe.
Preparation of methyl 8c, 11c‐octadecadienoate‐17,17,18,18‐d4 and methyl 8c,11c,14c‐octadecatrienoate‐17,17,18,18‐d4
Authors: Adlof R. O. , Emken E. A.
Published: October 2006

Multi‐gram quantities of methyl 8c,11c‐octadecadienoate‐17,17,18,18‐d4 and methyl 8c,11c,14c‐octadecatrienoate‐17,17,18,18‐d4 were synthesized for use in human metabolism studies. The deuterium atoms were incorporated using tris(triphenylphosphine)chlororhodium (I) catalyst and deuterium gas. The double bonds in the Δ11 and Δ14 positions were incorporated by acetylenic coupling. The double bond in the Δ8 position was introduced by the Wittig coupling of the mono‐ or di‐unsaturated triphenyl phosphonium halide to 7‐formylheptanoate. The 15‐25% trans isomers formed by the Wittig coupling reaction were removed by silver resin chromatography. Overall yields were 15%, for the diene ester (an 8‐step synthesis) and 12%, for the triene (a 12‐step synthesis). Both compounds were shown to have an isotopic purity of > 97% d4.
Synthesis of 14C‐labelled butoxyethoxyethanol
Authors: Thijssen J. B. A. , Janssen C. G. M. , Verluyten W. L. M. , Heykants J. J. P.
Published: October 2006

Butoxyethoxyethanol1, an organic solvent used as carrier in the levamisole pour‐on formulation, was synthesized via a Makosza etherification of 1‐14C‐ labelled bromobutane with mono tetrahydropyranyl (T.H.P.) protected diethylene glycol and subsequent removal of the T.H.P. protecting group. The compounds' synthetic yield was 88.8 %; it had a specific activity of 32.5 mci/mmol. The reaction product was radiochemically pure (99.6 %) according to high‐performance liquid chromatography and thin‐layer chromatography in three solvent systems.
Syntheses, resolution optique et radiolyse d' Acides Amines Trities a Haute Activite Specifique. I ‐ D,L‐Lysine (3H‐4,5,6,6); L‐lysine (3H‐4,4,5,5); L‐Leucine (3H‐4,5,5,5); Acide D‐α‐amino Adipique (3H‐4,4,5,5); Acide γ‐Amino Butyrique (3H‐2,2,3,3)
Authors: Ego Dominique , Beaucourt Jean‐Pierre , Pichat Louis
Published: October 2006

2,6‐Diamino‐4‐hexynoic acid 5 was prepared from 1,4‐dichloro‐2‐butyne and diethyl acetamidomalonate. The catalytic reduction of 5 with tritium led to (4,5,6,6‐3H) DL‐lysine 6′ spec. act. 113 Ci/mM. The catalytic reduction With tritium of L‐2‐amino‐6‐t‐butoxycarbonylamino‐4‐hexynoic acid 7 followed by hydrolysis gave [4,4,5,5‐3H] L‐lysine 6 spec. act. : 120 Ci/mM.

DL‐2‐amino‐5,5‐dichloro‐4‐methyl‐4‐pentenoic acid 11 was prepared from 2‐methyl‐1,1,3‐trichloro‐1‐propene and diethyl acetamidomalonate. The optical isomers Were separated by preparative HPLC. The catalytic reduction of the L enantiomer gave [4,5,5,5‐3H] L‐leucine 13 spec. act. 140 Ci/mM.

Ethoxycarbonylation of ethyl 2‐acetylamino‐2‐ethoxycarbonyl 4‐pentynoate : 15 in presence of palladium gave triethyl 4‐acetylamino‐1‐butyne‐1,4,4‐tri‐carboxylate 16. Reduction of 16 with tritium followed by hydrolysis gave DL‐[4,4,5,5‐3H]α‐aminoadipia acid 18′ spea. act. 130 Ci/mM. The oxidation of 18′ with L‐aminoxidase led to D‐α‐aminoadipia acid 18 with the same specific activity.

Methoxycarbonylation of 3‐phthalimido‐1‐propyne 19 in presence of Pd gave methyl 4‐phthalimido‐2‐butynoate 20 which tritiation followed by hydrolysis led to [2,2,3,3‐3H] GABA 22 spec. act. 109 Ci/mM. 3H NMR analyses Were carried out in each case. Studies on the self radiolysis of these aminoacids during storage are reported.
Synthesis of seven deuteromethyl‐caffeine analogues observation of deuterium isotope effects on cmr analysis
Authors: Falconnet J. B. , Brazier J. L. , Desage M.
Published: October 2006

This article describes synthesis of all 7 N‐trideuteromethyl isotopomers of caffeine by reaction of trideuteromethyl iodide (C2H3I) with the appropriate xanthine molecules.

The use of proton. deuterium and carbon‐13‐NMR as a first step in purity assessment revealed 13C‐NMR deuterium isotope effects on the resonance of perdeuteromethyl carbons.
Synthesis of deuterium labelled fluphenazine utilising borane reduction
Authors: Sardessai M. S. , Brander M. J. , Midha K. K. , Hawes E. M.
Published: October 2006

Two new procedures are described for the preparation of di‐ and tetra‐deuterated 10‐[[3‐[4‐(2‐hydroxyethyl)‐1‐piperazinyl]propyl]]‐2‐trifluoromethyl‐10H‐phenothiazine (fluphenazine). Deuterium was introduced in either the 1‐ or the 1‐ and 3‐positions of the propyl side chain by reduction with deuterated borane in tetrahydrofuran of the appropriately substituted N‐10 amide or amido ester. The isotopic purity of the synthesized deuterated products was greater than 99%.
Chiral Synthesis of Regiospecifically Deuterated 3‐Methylcyclohexanones
Authors: Kallmerten James , Knopp Michael A. , Durham Lisa L. , Holak Ingaborga
Published: October 2006

The enantioselective synthesis of deuterated 3‐methylcyclohexanones 1‐4 is described.
Synthesis of 14C‐ and 2H‐labeled 1,3‐dihydro‐3,3‐dimethyl‐5‐(1,4,5,6‐tetrahydro‐6‐oxo‐3‐pyridazinyl)‐2H‐indol‐2‐one (LY195115), an orally effective positive inotrope
Authors: Robertson David W. , Krushinski Joseph H. , Kau Don
Published: October 2006

We have synthesized 14C‐ and 2H‐labeled 1,3‐dihydro‐3,3‐dimethyl‐5‐(1,4,5,6‐tetrahydro‐6‐oxo‐3‐pyridazinyl)‐2H‐indol‐2‐one (LY195115), an extremely potent, orally‐effective cardiotonic with inotropic and vasodilator activities. The 14C‐label was introduced in the antepenultimate step by reaction of a β‐chloroketone precursor with Na14CN; acid‐catalyzed hydrolysis and cyclization with hydrazine provided the tetrahydropyridazinone bearing the 14C‐label in the oxo‐carbon. 1,3‐Dihydro‐3,3‐di(methyl‐d3)‐2H‐indol‐2‐one was prepared by exhaustive methylation of 1‐acetyl‐1,3‐dihydro‐2H‐indol‐2‐one with sodium hydride and iodomethane‐d3, followed by removal of the nitrogen protecting group. This labeled material was converted in two steps to [2H6]‐LY195115.
N.C.A. [18F]‐labelling of aliphatic compounds in high yields via aminopolyether ‐ supported nucleophilic substitution
Authors: Block Dirk , Klatte Bernd , Knöchel Arndt , Beckmann Rainer , Holm Uwe
Published: October 2006

The nucleophilic introduction of n.c.a. ‐ [18F]‐fluoride into alkanes and carboxylic acids using anion activation by macrocyclic polyethers was investigated.

The reactions carried out in the presence of the bicyclic aminopolyether APE 2.2.2. gave rise to high radiochemical yields (40‐65 %) under mild conditions. Important for the successful 18F‐labelling is a suitable cation/polyether couple, which leads to an unsolvated [18F]‐fluoride in a dipolar aprotic solvent and ensures a high ion concentration, thus enhancing the reactivity. Reaction parameters, such as concentration of substrate and APE, the influence of cation, anion and water were studied and optimised.
A simple one‐pot synthesis of cyclopropane [11C]carbonyl chloride. Synthesis and biodistribution of [11C]cyclorphan
Authors: McPherson Daniel W. , Hwang Dah‐Ren , Fowler Joanna S. , Wolf Alfred P. , Macgregor Robert M. , Arnett Carroll D.
Published: October 2006

A rapid, one‐pot, synthesis of cyclopropane [11C]carbonyl chloride was developed. This synthesis proceeded in 80% radiochemical yield (EOB) in a synthesis time of 10 minutes. This acid chloride was then used to synthesize a model compound, [11C]cyclorphan, by alkylation of norlevorphanol followed by reduction of the intermediate [11C]amide in an overall synthesis time of 55 minutes and a radiochemical yield of 15% (EOB). The biodistribution of [11C]cyclorphan in control and naloxone pretreated mice showed non‐specific binding and rapid clearance from brain.
Syntbesis of 14C‐labeeed felbamate from phenylacetic‐(methylene‐ 14C) acid
Authors: Choi Yong M. , Kucharczyk Norbert , Sofia R. Duane
Published: October 2006

A synthetic procedure for the preparation of 2‐phenyl‐1,3‐propanediol‐2‐14C dicarbamate. starting with phenylacetic‐(methylene‐14C) acid was developed. The procedure from phenylacetic acid to 2‐phenyl‐1,3‐propanediol dicarbamate has four steps via phenylmalonic acid and 2‐phenyl‐1,3‐propanediol. The overall yield of all four steps was 28%.
Synthesis of 4‐(3‐t‐butylamino‐2‐hydroxypropoxy)‐benzimidazol‐2(11c)‐one (cgp 12177)
Authors: Boullais C , Crouzel C , Syrota A
Published: October 2006

4‐(3‐t‐butylamino‐2‐hydroxypropoxy)‐benzimidazol‐2 (11C)‐one (CGP 12177) was synthetized in a short time (30 min) and with a specific activity of 130 mCi/μMol for β receptor studies by the positron emission tomography. The radioactive reagent was 11C‐phosgene and the starting material 1‐(3‐t‐butylamino‐2‐hydroxypropoxy)‐2.3‐diamino benzene.
14C‐labeling of a novel fungicide. I. Syntheses of optically active (E)‐and (Z)‐1‐(2,4‐dichlorophenyl)‐4,4‐dimethyl‐2‐(1,2,4‐triazol‐[14C]‐1‐YL)‐1‐penten‐3‐OLS
Authors: Nakatsuka Iwao , Kanamaru Hiroshi , Kamada Takeshi , Kawahara Kazuo , Yoshitake Akira
Published: October 2006

A novel fungicide, (‐)(E)‐1‐(2,4‐dichlorophenyl)‐4, 4‐dimethyl‐2(1,2,4‐triazol‐1‐yl)‐1‐penten‐3‐ol (S‐3308 L) and its three optically active stereoisomers were labeled with carbon‐14 at the triazole ring for use in the metabolic and environmental fate studies. 1,2,4‐Triazole‐14C (4) prepared from formamide‐14C (3) was treated with bromopinacolone to give triazolylpinacolone‐14C (5), which was condensed with 2,4‐dichlorobenzaldehyde giving (Z)‐ketone‐14C (6). (Z)‐Ketone‐14C (6) was photoisomerized to (E)‐ketone‐ 14C (7), which was reduced to racemic (Z)‐S‐3308‐ 14C (1) in 20% yield from 3. Reduction of 6 gave racemic (Z))S‐3308‐14C (2) in 23% field from 3. Optical resolution of both racemates 1 and 2 by a HPLC method with a chiral column gave (‐)(E)‐, (+)(E)‐, (‐)(Z)‐ and (+)(Z)‐1‐(2,4‐dichlorophenyl)‐4,4‐dimethyl‐2‐(1,2,4‐triazol‐[14C]‐1‐yl)‐1‐penten‐3‐ols (1a, 1b, 2a and 2b) in essentially Quantitative yields.
Synthesis of 3h‐labelled enalapril maleate
Authors: Bartroli J. , Ramis J. , Marin A. , Forn J.
Published: October 2006

The synthesis of enalapril maleate (MK 421) labelled with tritium at its proline ring is described. Thus, the N′‐hydroxysuccinimidyl ester of a N‐carboxyalkyl alanine derivative was reacted with L‐[4,5‐H] proline and the crude reaction mixture treated with maleic acid to give the maleate salt of enalapril in 27% yield.
A rapid synthesis of [82Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [82Br]‐ 2‐deoxy‐2‐bromo‐D‐glucose using D‐glucal as precursor
Authors: Homma Yoshio , Murase Yuko , Ishii Michiko , Sonehara Kazue
Published: October 2006

A new rapid synthesis of [82Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [82Br]‐2‐deoxy‐2‐bromo‐D‐glucose is described. Reaction of 82Br2 with D‐glucal in CHCl3, followed by treatment with 1 N HCl gave [82Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [82Br]‐2‐deoxy‐2‐bromo‐D‐glucose in the yield of 61.1 % and 27.7 %, respectively. The synthesis time was 20 min. The radiochemical purity of [82Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [82Br]‐2‐deoxy‐2‐bromo‐D‐glucose was greater than 95 %. The radiochemical yield of [82Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [82 Br]‐2‐deoxy‐2‐bromo‐D‐glucose was 14.3 % and 31.6 %, respectively. D‐Glucal was shown to be a useful precursor to allow rapid production of usable amounts of glucose analogs such as [75Br]‐2‐deoxy‐2‐bromo‐D‐mannose and [75Br]‐2‐deoxy‐2‐bromo‐D‐glucose.
Ochratoxin A labelled with 14C or 3H in the phenylalanine moiety
Authors: Hult Karl
Published: October 2006

Ochratoxin A is a mycotoxin produced by Aspergillus and Penicillium moulds. The toxin is an amide formed between phenylalanine and the isocoumarin acid ochratoxin α. Ochratoxin A with high specific radioactivity can be obtained, by substitution of the natural phenylalanine for 14C or 3H‐labelled phenylalanine. Labelled ochratoxin A was formed by condensation of labelled phenylalanine ethylester with an anhydride derivative of ochratoxin α. The intermediate O‐acetyl ochratoxin C was hydrolyzed with pig liver esterase and chymotrypsin to afford ochratoxin A. The overall yield of radioactivity was 50%. Specific activities up to 500 Ci/mol and 100 Ci/mmol for 14C and 3H respectively were obtained.
Methodes de Syntheses de l'idazoxan ‐ RX: 781094 [( Imidazolinyl‐2 ) ‐2‐Benzodioxanne‐1,4]Marque au Tritium a Haute Activite Specifique: Un Ligand Radioactif Antagoniste Selectif des α2‐Adrenorecepteurs Presynaptiques
Authors: Guillaumet G. , Coudert G. , Clement R. , Ponchant P. , Pichat L.
Published: October 2006

Four methods of syntheses of IDAZOXAN (RX 781094): |2‐(2‐imidazolinyl)‐1,4‐benzodioxane| labelled with tritium: 1 at high specific activity, a selective radioligand presynaptic α2‐ adrenoreceptor antagonist are described. 2‐carbethoxy‐1,4‐benzodioxine 5 was treated with tritium in benzene in presence of Wilkinson's catalyst leading to 2‐carbethoxy [2,3‐3H]‐1,4‐benzodioxane: 6 spec. act. 60 Ci/m which was then condensed in toluene with a reagent made from trimethylaluminium and ethylenediamine giving rise to 1 specific activity 44 Ci/mMole.

2‐(carbamido N‐cyanomethyl)1,4‐benzodioxine: 2 was prepared from 2‐chlorocarbonyl‐1,4‐benzodioxine: 10 and 2‐aminoacetonitrile. 2 was reduced with tritium in trifluoroacetic acid in presence of Pd/C giving 8 which, without purification was ring closed into 2 by trimethylaminium treatment. Spec. act. 35.5 Ci/mMole. When reduced with tritium in presence of Wilkinson's catalyst, 7 gave 9 spect. act. 55 Ci/mMole. After purification 9 was again reduced with tritium in trifluoroacetic acid in presence of Pd/C, or PtO2, or Rh/Al2O3 giving 8 which was cyclised into 1 by trimethylaluminium treatment in toluene. spec. act. of 1 was 41.5 ‐ 39 Curies/mMole. 1 was purified by successive preparative thin layer chromatography. The radiochemical purity checked by TLC and PLC was better than 99%. Some observations on the rate of self radiolysis of 1 are reported.
Synthesis of 14C‐bucromarone succinate and hydrochloride
Authors: Nicolas Colette , Verny Michel , Maurizis Jean‐Claude , Payard Marc , Faurie Michel
Published: October 2006

14C‐Bucromarone, 2‐[4‐(3‐N,N dibutylamino propoxy) 3,5‐dimethyl benzoyl] chromone, was synthesized from (U‐14 C) oxalic acid. The labelling takes place at the first step of the synthesis, and allowed the obtention of −14C‐Bucromarone succinate, with a specific activity of 7.45 mCi/mmol, i.e. 275.6 MBq/mmol; −14C‐Bucromarone hydrochloride, with a specific activity of 7.5 mCi/mmol, i.e. 277.5 MBq/mmol.
Synthesis of S‐adenosyl‐L‐homocysteine and 5′‐methylthioadenosine specifically tritiated at the 5′C position
Authors: Guillerm G. , Galas M. C. , Le Goffic F. , Beaucourt J. P. , Sergent L.
Published: October 2006

S‐adenosyl‐L‐homocysteine and 5′‐methylthioadenosine were bitritiated specifically at C′‐5 for enzymatic assay of S‐adenosylhomocysteine nucleosidase (EC.3.2.2.9).
Synthesis of [14C]alaproclate
Authors: Gawell Lars
Published: October 2006

The synthesis of carbon‐14 labelled alaproclate from [2‐14C]acetone in three steps is described. The label is introduced by the reaction of a benzylic Grignard reagent with the ketone yielding a tertiary alcohol Subsequent esterification with an α‐bromocarboxylic acid chloride and a.ination furnished the title compound in a 13% overall radiochemical yield.
A facile synthesis of 4′‐[2H]‐uridine and its derivatives
Authors: Ajmera Sudhir , Massof Steven , Kozarich John W.
Published: October 2006

A facile method for the introduction of deuterium at the C4, position of uridine and its derivatives involves the reaction of appropriately protected 4′,5′‐unsaturated pyrimidine nucleosides with B2D6, followed by hydrogen peroxide oxidation under alkaline conditions. The method described herein is also adaptable to the introduction of tritium at C4, position of pyrimidine nucleosides for use in mechanistic studies of DNA‐degrading drugs.
Synthesis of stable isotope enriched metabolites of theophylline
Authors: Matjeka Edward R. , Banks Richard C. , Mercer Gary D. , Musser Beth , Vestal Robert E.
Published: October 2006

Four isotopically labelled metabolites of theophylline were synthesized. The syntheses of 1‐(methyl‐d3 luric‐2,8‐13C2‐acid; 1,3‐di( methyl‐d3)uric‐2,8‐13C2 ad d; 3‐(methyl‐d3lxanthi ne‐2‐13C. 7‐15N and 1‐ (methyl‐d3)xanthine‐2‐13C are described. Modifications in published procedures for the synthesis of the corresponding unlabelled compounds were required to achieve the micro scale necessary to accommodate the small starting quantities of expensive stable isotope labelled precursors.
Synthesis of 1‐(2,3‐dihydroxypropyl)‐2‐nitro‐1H‐imidazole‐2‐14C and N‐(2‐hydroxyethyl)‐2‐(2‐nitro‐1H‐imidazol‐1‐YL‐2‐14C) acetamide
Authors: Fong Mary T. , Leaffer Morris A.
Published: October 2006

We have prepared the 14C‐labeled analogs of NSC 261036, 1‐(2,3‐dihydroxypropyl)‐2‐nitro‐1H‐imidazole‐2‐14C, and NSC 301467, N‐(2‐hydroxyethyl)‐2‐(2‐nitro‐1H‐imidazol‐1‐y1‐2‐14C) acetamide, for pharmacological, drug distribution, and mechanisms of action studies. The latter is an analog designed for lower toxicity and improved properties. The former is a metabolite of, and appears to be less toxic than, misonidazole.
The preparation of regiospecific tritiated and deuterated dibenzacridines by catalytic exchange and [14‐14C]dibenz‐[a,j]acridine
Authors: Rosario Christopher A. , Duke Colin C. , Gill Jennifer H. , Dawson Michael , Holder Gerald M. , Ghazy Tahany , Long Mervyn A.
Published: October 2006

A practical synthesis of [14‐3H]dibenz[a,j]acridine and [7‐3H]dibenz[a,h]acridine is reported from the parent hydrocarbon by catalytic exchange with tritium gas in the presence of palladium on calcium carbonate. Analogous regiospecific labelling with deuterium was also affected. In addition [14‐14C]dibenz[a,j]acridine was prepared from [14C]paraformaldehyde.
Syntheses of [2‐14C]penem antibacterials; (FCE 22101 and FCE 22891)
Authors: Fontana Erminia , Alpegiani Marco , Perrone Ettore , Vicario Gian Piero
Published: October 2006

The synthesis of FCE 22101 (sodium (5R,6S)‐6‐[(1R)‐hydroxyethyl]‐2‐carbamoyloxymethylpenem‐3‐carboxylate) labelled with carbon‐14 in the 2‐position of the penem system ring was performed in eight steps, using sodium salt of [1‐14C]glycollic acid 1 as the labelled starting material. The final product, penem [2‐14C]FCE 22101 11, was obtained in an overall radiochemical yield of 21%, 98% radiochemically pure and with a specific activity of 641 MBq/mmol (17.3 mCi/mmol). The acetoxymethyl ester FCE 22891 12 was prepared by condensation of 11 with bromomethyl acetate, with a yield of 41%.
Synthesis of diethylene triamine pentaacetic acid (DTPA) conjugated antibodies
Authors: Keeling A. A. , Bradwell A. A.
Published: October 2006

Antibodies labelled with radioisotopes via chelating agents are being used increasingly for in vivo localisation or radiotherapy of tumours. The most widely used chelating agent is DTPA. Here, we describe technical modifications of the standard DTPA cyclic anhydride conjugation procedure and determine the in vitro stability of the DTPA‐antibody conjugates. The use of this derivative of DTPA combined with the use of appropriate buffers and small disposable gel filtration columns resulted in the development of a simpler and more rapid technique for the production of DTPA‐conjugated antibodies.
Synthesis of [18‐14C]octatriacontane from [1‐14C]stearic acid
Authors: Hassam Saifunnissa B.
Published: October 2006

A method was developed to synthesize 14C‐labelled n‐alkanes for use in cigarette smoke studies. Specifically, n‐[18‐14C]‐octatriacontane was synthesized from 1 mCi [1‐14C]stearic acid in a radiochemical yield of 20%. The key features of this synthesis were two consecutive alkylations of tosylmethyl isocyanide followed by acid hydrolysis to [18‐14C]‐19‐octatriacontanone and modified Wolff‐Kishner reduction to the n‐alkane. After purification on silica gel 25 mg of [18‐14C]octatriacontane was obtained with a total radioactivity of 200 μCi, a specific activity of 4.3 mCi/mmol, and a radiochemical purity in excess of 98% by thin layer radiochromatography. The method has also been applied to the synthesis of unlabeled n‐pentatriacontane and is considered to be generally applicable to the synthesis of radiolabeled alkanes from radiolabeled fatty acids.
Synthesis of highly tritiated 7‐deoxy‐7 dihydroantheridiol and antheriodiol
Authors: Meyer Michael D. , Carlson Gerald L. , Toft David O. , Greaves Austin M. , Ng Kam‐Mui Eva , McMorris Trevor C.
Published: October 2006

The synthesis of tritiated male‐activating steroids of the aquatic fungus Achlya, 7‐deoxy‐7‐dihydroantheridiol (7‐DA) and antheridiol, has been achieved by aldol condensation of 3β‐acetoxy‐23,24‐dinorchola‐1,5‐dien‐22‐al and the carbanion of 3‐isopropyl‐2‐butenolide. The product with the desired stereochemistry (22S,23R) was isolated and reduced with 3H2 in the presence of tris(triphenylphosphine)rhodium chloride. Acid hydrolysis of the acetate gave 1,2[3H]‐7DA which had a specific activity of 40 Ci/mmol. 1,2[3H]‐7DA was converted to 1,2[3H]‐antheridiol by protecting the hydroxyl groups as the disilyl ethers, oxidation to the 7‐ketone with chromium trioxide‐dimethylpyrazole and removal of the protecting groups by gentle acid treatment. 1,2[3H]‐7DA has been used to detect a protein receptor in the cytosol of Achlya.
Synthesis of 13C‐labeled polychlorinated biphenyls
Authors: Roth Robert W. , Heys J. Richard , Saugier Joseph H. , Chien David H. T. , Rotert Gary A. , Erickson Mitchell D.
Published: October 2006

Methods are described for the synthesis of 4‐chloro(1prime;,2prime;,3prime;,4prime;,5prime;,6′‐13C6)biphenyl; 3,3′,4,4′‐tetrachloro(13C12)biphenyl; and 2,2′,3,3′,5,5′,6,6′‐octachloro(13C12)biphenyl; decachloro(13C12)biphenyl from (13C6)benzene of ≧ 99 atom % isotopic purity, on scales of 100 mg to 1 g. The gas chromatographic retention time of each 13C‐polychlorinated biphenyl (PCB) matched that of the corresponding unlabeled commercial reference standard, and the mass spectrum of each compound was consistent with an isotopic purity of ≧ 99 atom % 13C. These compounds are useful as recovery surrogates and internal standards in the determination of PCBs in a variety of complex matrices.
High yield synthesis of 14C labelled intermediates of the L‐type pentose pathway: Octulose mono‐ and bisphosphates, sedoheptulose 1,7‐bisphosphate and D‐arabinose 5‐phosphate
Authors: Arora Krishan K. , Macleod John K. , Williams John F.
Published: October 2006

Methods for the enzymic synthesis, isolation, purification and analysis of the 14C labelled intermediates that are characteristic of the L‐type pentose phosphate pathway are described. These are D‐glycero D‐ido octulose 1, 8‐bisphosphate and 8‐monophosphate; D‐glycero D‐altro octulose mono‐ and bisphosphates; sedoheptulose 1,7‐bisphosphate and D‐arabinose 5‐phosphate. The procedures for the preparation of octulose‐ and sedoheptulose bisphosphates are based on the aldolase‐catalyzed condensation of dihydroxyacetone phosphate with appropriately 14C‐labelled aldo pentose 5‐phosphates and erythrose 4‐phosphate respectively. D‐Glycero D‐ido octulose 8‐phosphate and its altro epimer were prepared in transketolase catalyzed reactions involving β‐hydroxypyruvate and appropriately 14C‐labelled aldohexose 6‐phosphates. [U‐14C] D‐arabinose 5‐phosphate was synthesized by reacting [U‐14C] glucosamine 6‐phosphate with ninhydrin. The authenticity of each of the 14C‐labelled sugar phosphates was confirmed using a variety of chromatographic methods, enzymatic analytic methods and NMR spectroscopy.

The 14C labelled compounds are used in investigations involving the search for the identity of the pentose pathway in tissues in vitro, for the measurement of L‐type pathway enzyme reactions and for testing the mechanistic predictions of the L‐type pathway in vitro.
Synthesis of tritium‐labelled 2‐(3′‐carboxypropyl)‐3‐imino‐6 para‐methoxy phenyl‐2,3‐dihydropyridazine ([3H] SR95531)
Authors: Gh A. Melikian , Schlewer G. , Hurt S. , Chantreux D. , Wermuth C. C.
Published: October 2006

The synthesis of tritium labelled 2‐(3′‐carboxypropyl)‐3‐imino‐6‐para‐methoxyphenyl‐2,3‐dihydropyridazine, a new, specific, water‐soluble and chemically stable GABA antagonist at the GABAA receptor site is reported. The synthesis involves an N‐2 endo‐alkylation of 3‐amino‐6‐p‐methoxyphenyl‐pyridazine with ethyl γ‐bromocrotonate, reductive tritiation of the crotonic double bond and hydrolysis in acidic medium.
Synthesis of 3‐([carbonyl‐14C]p‐anisoyl)‐1‐(2‐morpholinoethyl)‐2‐methylindole maleate
Authors: Johnston D. , Duncan D. D.
Published: October 2006

A synthetic procedure for producing 3‐([carbonyl‐14C]p‐anisoyl)‐1‐(2‐morpholinoethyl)‐2‐methylindole maleate is described. The synthesis is achieved in two steps from 1‐(2‐morpholinoethyl)‐2‐methylindole utilising [carbonyl‐14C]p‐anisoyl chloride as the source of the radiolabel with an overall chemical yield of 39% and a radiochemical yield of 28%.
Preparation of all stereoisomers of 14C‐labelled 3‐(2,2‐dichloroethenyl)‐and 3‐(2,2‐dibromoethenyl)‐2,2‐dimethylcyclopropanecarboxylic acids
Authors: Kanamaru Hiroshi , Kawahara Kazuo , Okuno Masami , Yoshitake Akira , Nakatsuka Iwao
Published: October 2006

The four 14C‐labelled stereoisomers of both 3‐(2,2‐dichloroethenyl)‐2,2‐dimethylcyclopropanecarboxylic acid and 3‐(2,2‐dibromoethenyl)‐2,2‐dimethylcyclopropanecarboxylic acid, the improtant acid components of various potent insecticidal pyrethroids, were prepared efficiently from [1‐14C]chrysanthemic acid (5) for use in comparative metabolic studies. α‐Bromo‐β‐naphthyl d,l‐cis, trans‐[1‐14C]chrysanthemate (6) was oxidized with osmium tetroxide‐sodium periodate to give the formyl ester (7) in 78% yield. Wittig reaction of 7 with dichloromethylenetris(dimethylamino)phosphorane at −75 ‐ −70 °C afforded the dichlorovinylated ester (8) quantitatively. Optical resolution of 8 by preparative HPLC using a chiral‐phase column led to the four stereoisomers (8a ‐ 8d) with optical purities more than 99%. Hydrolyses of the esters (8a ‐ 8d) yielded the corresponding optically active 3‐(2,2‐dichloroethenyl)‐2,2‐dimethyl [1‐14C]cyclopropanecarboxylic acids (1a ‐ 1d) quantitatively. Similarly, Wittig reaction of the formyl ester (7) with dibromomethylenetris(dimethylamino)phosphorane, followed by optical resolution and hydrolysis, gave four optically active 3‐(2,2‐dibromoethenyl)‐2,2‐dimethyl [1‐14C]cyclopropanecarboxylic acids (2a ‐ 2d) in considerably high yields.
Syntheses of 14C and 3H labelled forms of donetidine ‐ A histamine H2‐antagonist
Authors: Armitage M A , Cashyap M M , Saunders D
Published: October 2006

Three syntheses of radiolabelled 2‐[2‐(2‐N,N‐Dimethylaminomethyl‐5‐furanyl‐methylthio)ethylamino]‐5‐(6‐hydroxy‐4‐picolyl)‐4‐pyrimidone trihydrochloride (donetidine trihydrochloride) are described. One describes the preparation of the free base, and two of its trihydrochloride.

. A five stage synthesis (Scheme 1) which gave 14C‐donetidine (8) labelled in the C2 position of the pyrimidone ring starting from barium [14C]cyanamide. The overall radiochemical yield for the synthesis was 9% to give (8) at a specific activity of 57.8mCi/mmol.

. A three stage synthesis (Scheme 2) which gave 14C2‐donetidine trihydrochloride (14) labelled in both methylenes of the aminoethylthio moiety starting from [1,2‐14C2]‐cysteamine hydrochloride. The overall radiochemical yield for the synthesis was 18% to give (14) at a specific activity of 15.4mCi/mmol.

. A five stage synthesis (Scheme 3) which gave 3 H‐donetidine trihydrochloride (22) labelled in the methylene of the furanlmethylthio moiety starting from sodium boro[3H]‐hydride. The overall radiochemical yield for the synthesis was 1% to give (22) at a specific activity of 33.7mCi/mmo1.
Synthèse de la diméthoxy‐6,7 (para‐chlorobenzyl)‐4 isoquinoléine, deutériée en position 3 ou marquée au 14C sur le méthylène benzylique
Authors: Bouvier P. , Mourlevat F. , Pichat L. , Servin A. , Viel C.
Published: October 2006

6,7‐dimethoxy‐4 (parachlorobenzyl) (D‐3) isoquinoline : 6 and 6,7‐dimethoxy‐4 [parachlorobenzyl (methylene 14C)] isoquinoline: 11 were prepared respectively by the condensation of α‐deuterio‐veratrylaminoacetaldehyde diethylacetal : 4 with parachlorobenzaldehyde and the reaction of parachlorobenzaldehyde (carbonyl 14C) : 9 with veratrylaminoacetaldehyde diethylacetal.
Synthesis of tritium labelled ropivacaine — A new potential local anesthetic
Authors: Gawell Lars
Published: October 2006

A potential local anesthetic, ropivacaine, is synthesized labeled with tritium. The label is introduced by reduction of a racemic tetrahydropyridine derivative with tritium gas. Resolution into the labeled enantiomers is accomplished by preferential crystallization with added carrier. The location of the tritium label is verified by 3H NMR.
Optimum labelling of monoclonal antibody 3El.2 with 111in using a bifunctional chelate
Authors: Reilly R. R. , Ege G. G.
Published: October 2006

Monoclonal antibody 3El.2 was coupled with the bifunctional chelate, cyclic DTPA anhydride, at molar ratios (cDTPAA:3El.2) of 1:1, 10:1, 100:1 and 1000:1. The desired substitution level of less than one mol of DTPA/mol of 3El.2 was achieved at a molar ratio of 10:1 and a coupling efficiency of 9.9±3.38 percent. The DTPA‐coupled antibody was purified by dialysis before labelling with 111In acetate. The labelling efficiency was 38.7±3.59 percent. The radiolabelled antibody was purified by PD‐10 Sephadex G‐25M chromatography then sterilized by filteration through a 0.22 um filter (Milex‐GS or Millex‐GV). A substantial adsorption effect (87.4±3.84 percent) occurs with the Millex‐GS filter but to a much smaller extent (26.8±5.58 percent) with the Millex‐GV filter. The radiochemical purity of the product was 80–90 percent depending on the method of analysis. The product was tested and found to be sterile and non‐pyrogenic.
Stereospecific synthesis of (R)‐[2‐2H1]‐glycine by means of microbial reduction and a determination of It's absolute configuration by CD spectra
Authors: Yamada Haruo , Kurumaya Katsuyuki , Eguchi Tomoko , Kajiwara Masahiro
Published: October 2006

A preparation of optically pure (R)‐[2‐2H1]‐glycine by microbial reduction is detailed. The reduction of [2‐2H]‐furfural and furfural with S. Cerevisiae in H2O and in D2O gave (S)‐ and (R)‐Labeled furfuryl alcohol respectively, which could be converted to the labeled glycine in three steps. A new method for the determination of the sense of chirality of the labeled glycine by means of CD spectra and an application of MTPA method for the determination of the optical purity are also described.
Sodium [1,2‐13C2, 2H3]acetate
Authors: Barber Jill , Howard Tina D. , Tearle James
Published: October 2006

Sodium [1,2‐13C2,2H3] acetate has been prepared on a small scale suitable for biosynthetic investigations.
An improved synthesis of ethanal‐1‐13C
Authors: Barbry Didier , Couturier Daniel
Published: October 2006

The title compound is obtained from sodium acétate‐1‐13C by a shorter synthesis than the usual one. In the last step, acetyl chloride‐1‐13C is reduced by tributyltin hydride with palladium (O) complexe.
Synthesis of 3‐amino‐1‐methyl‐9H‐[4‐14C]pyrido[3,4‐b]indole (3‐amino[4‐14C]harman)
Authors: Tada Masao , Sato Kazunori , Oikawa Atsushi
Published: October 2006

A seven‐step synthesis of 3‐amino‐1‐methyl‐9H‐[4‐14C]pyrido‐[3, 4‐b]indole from DL‐[methylene‐14C]tryptophan and acetaldehyde is described.
Possible drugs labelled with 14C. III. Synthesis of D‐[3‐14C]phenylalaninyl‐L‐propyl‐L‐arginine aldehyde and L‐tyrosinyl‐D‐methionyl‐glycyl‐L‐[3‐14C]phenylalaninyl‐L‐proline amide
Authors: Koltai E. , Bajusz S. , Széll E. , Zólyomi G.
Published: October 2006

D‐[3‐14C] Phenylalaninyl‐L‐prolyl‐L‐arginine aldehyde (GYKI‐14166) and L‐tyrosyl‐D‐methionyl‐glycyl‐L‐ [3‐14C] phenylalaninyl‐L‐proline amide (GYKI‐14238) were prepared starting from D‐ [3‐14C] phenylalaninyl‐L‐proline and L‐ [3‐14C] phenylalaninyl‐L‐proline, respectively. The diastereomeric pairs obtained by coupling 2,4,5‐trichlorophenyl benzyloxycarbonyl‐D,L‐[3‐14C] phenylalaninate to L‐proline and by subsequent deprotection were separated on silica gel.
Synthesis of [6β,7β‐2H]‐ and [6β,7β‐3H]‐21‐hydroxy‐19‐norpregn‐4‐ene‐3,20 dione
Authors: Arunachalam Thangavel , Gut Marcel
Published: October 2006

The (6β,7β‐2H) and (6β,7β‐3H) labelled 19‐nordeoxycorticosterone 6 was prepared by selective catalytic hydrogenation of 21‐hydroxy‐19‐norpregna‐4,6‐diene‐3,20‐dione (5) which in turn was synthesized from 19,21‐dihydroxypregna‐4,6‐diene‐3,20‐dione (1).
Synthesis of carbon‐14 labeled 1‐(4‐methoxybenzoyl)‐5‐oxo‐2‐pyrrolidinepropanoic acid (CI‐933)
Authors: Huang C. C.
Published: October 2006

1‐(4‐Methoxybenzoyl)‐5‐oxo‐2‐pyrrolidinepropanoic acid (CI‐933) (17), a new cognition activating agent, was radiolabeled with carbon‐14. The synthesis was accomplished using bromo[1‐14C]acetic acid as the starting material. A facile one‐pot synthesis of an α,β‐unsaturated ester 10 from an alcohol 2 and a Wittig reagent 15 in the presence of Dess‐Martin periodinane was developed.
Synthesis of tritiated β‐(S‐benzylmercapto)‐β,β‐cyclopentamethylene propionic acid
Authors: Landvatter Scott W. , Heys J. Richard
Published: October 2006

β‐(S‐benzylmercapto)‐β,β‐cyclopentamethylene propionic acid has been tritium labeled in the cyclohexyl ring. A key feature of the synthesis is the reduction of phenolwith tritium gas over catalyst giving tritiated cyclohexanone. A Wadsworth‐Emmons reaction followed by esterase hydrolysis of the resulting ester and Michael addition of p‐methylbenzylmercaptan afford the title compound.
Synthesis of deuterated and tritiated gossypol
Authors: Stipanovic Robert D. , Williams Howard J. , Muehleisen David P. , Plapp F. W.
Published: October 2006

We report here the synthesis of deuterated and tritiated gossypol by exchange with labelleled water using trifluoroacetic acid as the catalyst. In the case of D2O in tetrahydrofuran, the exchange is complete in 45 minutes at 75°C as determined by a 1H‐NMR spectrum.
Synthesis of [14C]‐labelled pelrinone
Authors: Hicks D. D. , Hangeland J. J.
Published: October 2006

[14C]Pelrinone (1,4‐dihydro‐2‐methyl‐4‐oxo‐6[(3‐pyridinylmethyl)‐amino]‐5‐pyrimidine‐[14C]‐carbonitrile hydrochloride; AY‐28,768 hydrochloride), a potent inotropic agent, was prepared by reacting chloroacetic acid with [14C]sodium cyanide to give the labelled cyanoacetic acid. The acid was esterified, converted to the bis‐S‐methyl compound, condensed with acetamidine hydrochloride, coupled with 3‐aminomethylpyridine, and treated with methanolic hydrochloric acid. Two batches of [14C]pelrinone were produced, giving a combined overall yield of 15.6% from [14C]sodium cyanide (sp. act. 66.2 ± 1.5 and 64.2 ± 1.9 μCi/mg; 98.8 and 98.0% radiochemical purity, respectively).
Photoaffinity analog of herbicide inhibiting cellulose biosynthesis: Synthesis of [3H]‐2,6‐dichlorophenylazide
Authors: Cooper Geoffrey , Delmer Deborah , Nitsche Carmen
Published: October 2006

The compound 2,6‐dichlorobenzonitrile (dichlobenil, DCB) is known to be a reversible inhibitor of in vivo cellulose biosynthesis in higher plants and algae. We now report the synthesis of 2,6‐dichlorophenylazide (DCPA) with a non‐exchangeable tritium label of high specific activity. We have shown this compound to compete with DCB in binding to cotton fiber extracts, and to specifically label a low molecular weight protein in this extract on irradiation with UV light.
The synthesis of high radiochemical purity of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose without the use of preparative hplc
Authors: Ginos James Z. , French Robert , Reamer Robert
Published: October 2006

A process is described for preparing routinely sterile and pyrogenfree, multimillicurie amounts of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose (18F‐2FDG) with and without carrier‐added fluoride and with a radiochemical purity of greater than 98% without the use of preparative HPLC. For 13 consecutive runs, the radiochemical yield with carrier‐added fluoride was 35.5 ± 2.2%. The [18F]fluoride used was produced by the reaction 160(3He, p) 18F or by the reaction 180 (p,n)18F. Analytical HPLC, 1H and 19F NMR spectral analysis were used to establish the identity and purity of 18F‐2FDG.
The synthesis of 13C labelled N, N′‐dimethyl 1‐chloro‐2‐naphthaleneethanimidamide monohydrochloride, a potential psychotherapeutic agent
Authors: Goralski Christian T. , McCarthy James R. , Kracht William R. , Nyquist Richard A.
Published: October 2006

N, N'‐Dimethyl 1‐chloro‐2‐naphthaleneethanimidamide monohydrochloride is a potential psychotherapeutic agent for which a sample of carbon‐13 labelled material was required for metabolism studies. A sample of 90% enriched N, N'‐dimethyl 1‐chloro‐2‐naphthaleneethanimidamide monohydrochloride was prepared from 90% carbon‐13 enriched potassium cyanide and 2‐methylnaphthalene in five steps. Chlorination of 2‐methylnaphthalene with sulfuryl chloride gave 1‐chloro‐2‐methylnaphthalene in 69% yield. Bromination of 1‐chloro‐2‐methylnaphthalene with N‐bromosuccinimide in carbon tetrachloride in the presence of catalytic benzoyl peroxide afforded 2‐(bromomethyl)‐1‐chloronaphthalene in 59% yield. Treatment of 2‐(bromomethyl)‐1‐chloronaphthalene with potassium cyanide in aqueous ethanol afforded 13C‐1‐chloro‐2‐naphthylacetonitrile in 89% yield. The nitrile was converted to the imidate ester hydrochloride in 89% yield under Pinner reaction conditions (1). This intermediate was treated with excess methylamine in ethanol at 40‐55°C to give the title compound in an overall yield of 27% from 2‐methylnaphthalene. The effects of the 13C labelling on the infrared and 1H and 13C NMR spectra of the intermediates and the final product are discussed.
Synthesis of 3H‐D‐ala2‐leu‐enkephalin‐chloromethyl ketone of high specific activity
Authors: Tóth G. , Hepp J. , Sirokmán F. , Medzihradszky K.
Published: October 2006

The enkephalin affinity reagent /3H/‐Tyr‐D‐Ala‐Gly‐Phe‐Leu‐CH2C1 //3H/‐DALECK/ was synthesized by fragment condensation. /3H/‐Boc‐Tyr‐D‐Ala‐Gly was prepared by catalytic tritiation of protected, iodinated tripeptide. The protected tritiated tripeptide and the Phe‐Leu‐CH2Cl dipeptide were condensed by the mixed anhydride method. The protecting group was removed by HCl‐methanol. The /3H/‐DALECK had a specific activity of 34, 2 Ci/mmole /1,27 TBq/mmole/.
Synthesis of [methoxy‐3H]‐ and [methoxy‐11C]‐ labelled raclopride. Specific dopamine‐D2 receptor ligands
Authors: Ehrin Erling , Gawell Lars , Högberg Thomas , de Paulis Tomas , Ström Peter
Published: October 2006

Radioactive labelled raclopride and its (R)‐isomer were prepared by O‐alkylation of the corresponding phenols with labelled methyl iodide. The syntheses of the two phenolic precursors from (R)‐ and (S)‐2‐aminomethyl‐1‐ethylpyrrolidine are described. Resolution of the racemic amine into the enantiomers was accomplished by fractional crystallization of the ditartrates. Coupling of the amines with 3,5‐dichloro‐2,6‐dimethoxybenzoyl chloride, followed by dealkylation, led to the diphenolic precursors. Mono‐alkylation of the corresponding precursor with [3H]methyl iodide furnished the potent dopamine‐D2 ligand [3H]raclopride and its (R)‐isomer. [11C]Methyl iodide was prepared from [11C]carbon dioxide. Subsequent reaction with phenolic (S)‐precursor furnished [11C]raclopride which has been used in positron emission tomography (PET) studies of the human brain.
Synthesis and stability of S‐(2‐carboxyethyl)‐N‐(2‐t‐butyl‐5‐methoxy‐benzthiazol‐6‐yl)‐[14C]dithiocarbamate [CGP 20376 (CGI 16483)]
Authors: Anjaneyulu B.
Published: October 2006

For pharmacokinetic and metabolism studies in laboratory animals, CGP 20376 labelled with carbon‐14 on the dithiocarbamoyl carbon atom in the side chain at 6‐position of the benzthiazolyl ring system and having a specific activity of 6.13 μCi/mg (2.35 mCi/mmol) was synthesized, in four steps, starting with potassium[14C]thiocyanate. At physiological pH (in vitro) [14C] CGP 20376 dissociated rapidly into its biologically active isothiocyanate precursor [14C] CGP 20308, indicating that it might behave as a pro‐drug.
Synthesis of carbon‐14 labeled 6‐(4‐fluorophenyl)‐5‐(4‐pyridyl)‐2,3‐dihydroimidazo[2,1‐b]thiazole (SK&F 86002)
Authors: Senderoff S. G. , Heys J. R. , Blackburn D. W.
Published: October 2006

SK&F 86002, 6‐(4‐fluorophenyl)‐5‐(4‐pyridyl)‐2,3‐dihydromidazo[2,1‐b]thiazole, was synthesized labeled with carbon‐14 at C‐1 or C‐2, 3 using either [14C]thiourea or 1,2‐dibromo [14C2] ethane, respectively. The synthetic route, involving the condensation of an asymmetric benzoin with thiourea followed by alkylation, gave a mixture of SK&F 86002 and structural isomer SK&F 86055, 5‐(4‐fluorophenyl)‐6‐(4‐pyridyl)‐2,3‐dihydroimidazo‐[2,1‐b]thiazole. The two products were separated easily by flash chromatography. The use of 1,2‐dibromo [14C2]ethane as the labeling reagent was superior to the use of [14C]thiourea in this sequence, for the radiolabel was incorporated in the final step of the synthesis by an alkylation reaction, thus providing greatly increased overall radiochemical yields.
Synthesis of 5‐(1′phenyl‐4′‐piperazinomethyl)‐2‐amino‐2‐oxazoline (cor 3224) labelled with carbon‐14
Authors: Luu‐Duc C. , Béney C. , Jarry C. , Feniou C.
Published: October 2006

Phenyl‐piperazinomethyl‐amino‐oxazoline 3 labelled with carbon‐14 was obtained in good yield in two steps from [14C]epichlorhydrin. Specific radioactivity: 19.40 μCi/mg; 5,09 mCi/mmol. Radiochemical yield: 50% of the theoretical amount.
The N.C.A. nucleophilic 18F‐fluorination of 1,N‐disubstituted alkanes as fluoroalkylation agents
Authors: Block Dirk , Coenen Heinz Hubert , Stöcklin Gerhard
Published: October 2006

This systematic study describes the preparation of bifunctional n.c.a. 18F‐fluoroalkanes using amino‐polyether (APE) supported nucleophilic substitution. With the APE (Kryptofix® 2.2.2.) potassium carbonate complex in acetonitrile n.c.a. 18F− is introduced into disubstituted alkanes ( X(CH2)nX, n = 1–3, X = Br, OMes, OTos) in high yields within 10–15 min. The substitution yield increases in the sequence of leaving groups Br < OMes < OTos and with increasing alkyl chain length. At substrate concentrations of 0.025 M of bistosyloxyethane a radiochemical yield of 82 ± 8% of [1‐18F]‐fluoroethyltosylate is obtained. This compound appears optimal as fluoroalkylation agent with respect to size, stability and ease of its preparation.
Relative efficiencies of tritium atoms and ionic species in peptide labeling
Authors: Hua Ruoling , Peng Chin‐Tzu
Published: October 2006

Glycylglycyl‐L‐leucine and glycyl‐L‐leucine dispersed on silica‐alumina and supported Ni catalyst, were labeled with tritium by microwave discharge activation of tritium gas, as a model to study the optimum condition for labeling peptides and proteins. In the reaction, decreasing the tritium pressure and increasing the microwave power promote the formation of tritium ions and result in an increase in specific activity of the labeled product. The highest specific activity was achieved with the adsorbate molecules as a monolayer on support. Under similar conditions, amino acids glycine and L‐leucine were less efficiently labeled than the peptides. Tritium atoms generated by mercury photosensitization with a uv light were less effective for labeling than tritium ions. Impurities in tritium gas can adversely affect the degree of tritium incorporation in peptides.
Synthesis of high specific activity carbon‐14 labeled PD‐113,926 and CI‐930, potential new cardiotonic agents
Authors: Hays Sheryl J. , Hicks James L. , Huang C. C.
Published: October 2006

Double‐labeled PD‐113,926 and CI‐930 were synthesized from [14C]MeI and [14C]BaCO3 respectively in high specific activity (>90 mCi/mmol). The synthesis of CI‐930 employed the intermediate 2‐butenenitrile‐3,4‐14C2 which was synthesized by a phase transfer Wittig procedure. This Wittig procedure is fast, produces moderate to good yields of olefin and accommodates the use of aqueous solutions of aldehydes.
The syntheses of 4‐aminobutanoic acid‐2,2‐2H2 and ‐4,4‐2H2 and progabide‐2,2‐2H2 and ‐4,4‐2H2
Authors: Davis Bruce
Published: October 2006

4‐Aminobutanoic acid‐2,2‐2H2 and ‐4,4‐2H2 were synthesized in high yield with high deuterium incorporation, and then converted into the corresponding deuterium‐labelled anti‐convulsant drug, progabide, by means of a transimination reaction.