bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of tritium labelled benzamide dopamine‐D2 lignads at high specific activity
Authors: Gawell Lars , Hall Häkan , Köhler Christer
Published: October 2006

A method for the preparation of tritium labelled potential neuroleptics of the benzamide class possessing highly potent dopamine‐ D2 binding properties, is described. The pyrrolidine moiety of the molecule is labelled with tritium by hydrogenation, to a specific activity of up to 58 Ci/mmol and subsequently reacted with an acid chloride. The specificity of the label is confirmed by 3H‐NMR.
Synthesis of 14C‐labelled dibenzo[d, g] [1,3,6]dioxazocine derivatives (EGYT‐2474 and EGYT‐2509)
Authors: Birkás‐Faigl E. , Engler J. , Zólyomi G. , Rózsa L.
Published: October 2006

Synthesis of 2‐chloro‐12‐(3‐dimethylaminopropyl)‐dibenzo[d, g] [1,3,6]dioxazocine maleate (EGYT‐2474) and 2‐chloro‐12‐(3‐dimethylamino‐2‐methylpropyl)‐di‐benzo[d, g] [1,3,6] dioxazocine hydrochloride (EGYT‐2509) labelled with 14C‐isotope is reported. The synthesis of above compounds was based on [14C] methylene diiodide which was prepared by the reduction of [14C]iodoform. [14C]Iodoform was synthesised by an improved method in a radiochemical overall yield of 44% calculated on barium [14C]carbonate.
Synthesis of 2‐[2‐14C]‐(2‐aminoethyl)‐thiazole dihydrochloride: Thiazolyl ethylamine dihydrochloride
Authors: Armitage M A , Saunders D
Published: October 2006

The histamine H1 agonist, 2‐[2‐14C]‐(2‐aminoethyl)‐thiazole dihydrochloride has been labelled with carbon‐14 in the 2 position of the thiazole starting from potassium [14C] cyanide. The overall radiochemical yield for the synthesis was 17% at a specific activity of 36mCi/mmol.
Synthesis of 11C‐suriclone
Authors: Boullais C. , Oberdorfer F. , Sastre J. , Prenant C. , Crouzel C.
Published: October 2006

11C‐Suriclone was synthetised in a short time (30 minutes) with a high specific activity (750 mCi/ m̈Mol) for studies in man with the Positron Emission Tomography technic. The starting material was the N‐demethylated product 35489 RP. The radioactive reagent was either 11C‐formaldehyde or 11C‐methyl iodide.
A convenient regio‐ and stereospecific synthesis of 2H‐labelled methyl trans‐chrysanthemate
Authors: Saljoughian Manoucher
Published: October 2006

The methyl ester of trans‐chrysathemic acid (a constituent of natural pyrethrins) has been regio‐ and stereospecifically deuteriated in the olefinic (76%D) and the cyclopropane ring (67%D) protons in a one stage synthesis as shown by 1H nmr spectroscopy.
Radioiodinations of organic molecules on silica gel surfaces
Authors: Boothe Thomas E. , Finn Ronald D. , Vora Manhar M. , Emran Ali , Kothari Paresh J. , Kabalka George W.
Published: October 2006

To investigate radioiodinations on chromatographic surfaces, 131I− has been allowed to react with various organic compounds on silica gel chromatography plates. Antipyrine, which reacts with 131I− to give 4‐[131I]iodoantipyrine, was used as a model compound. The yield varied as a function of the initial solvent used; hydrogen ion concentration; contact time on the surface; and temperature. These results were extended to other reactive compounds such as substituted 3H‐pyrazol‐3‐ones; substituted phenols, including L‐tyrosine; substituted anilines; 5‐iodouracil; some secondary alkyliodides and alkylbromides; alkylboranes; and aryl‐and vinylboronic acids.
Synthesis of oxygen‐17 labeled thyrotropin releasing hormone
Authors: Ponnusamy E. , Fiat D.
Published: October 2006

Oxygen‐17 isotope was introduced into the α‐carboxyl group of L‐proline and L‐pyroglutamic acid by acid catalysed exchange of oxygen‐17 from H2 17O or acid hydrolysis of respective amino acid methyl esters in presence of HCl/H2 17O. The α‐amino group of the amino acids were protected by tertbutyloxycarbonylation. Two analogues of thyrotrop in releasing hormone, one enriched with [17O] at the proline carboxamide oxygen (I) and the other at the pyroglutamic acid's amide oxygen (II) were synthesized using Merrifield method of solid phase peptide synthesis.
Synthesis of tritium labelled DSP 4, a selective noradrenaline neurotoxin
Authors: Sahlberg Christer , Gawell Lars
Published: October 2006

DSP 4 (N‐(2‐Chloroethyl)‐N‐ethyl‐2‐bromobenzylamine, 1) is a neurotoxin, selective for neuronal noradrenaline (NA). Tritium labelled DSP 4 (4) with a specific activity of 105 mCi/mmol was prepared. The key step in the synthesis is a reduction of the aminoester 2 with activatated sodium boro [3H]hydride thus forming the alcohol 3.
Synthesis of 1,2,3,4‐tetrahydronaphthalene‐1‐13C, naphthalene‐1‐13C, and 1‐naphthalenol‐1‐13C
Authors: Pickering R. E. , Bymaster D. L. , Eisenbraun E. J.
Published: October 2006

The synthesis of 1,2,3,4‐tetrahydronaphthalene‐1‐13C, naphthalene‐1‐13C, and 1‐naphthalenol‐1‐13C in 98, 81, and 82% overall yields respectively from 4‐phenylbutanoic‐1‐13C acid is described.
Synthesis of 1,3,5‐TRI(nitro‐15N)‐1,3,5‐hexahydrotriazine, RDX‐(15NO2)3
Authors: Sitzmann Michael E.
Published: October 2006

The synthesis of 1,3,5‐tri(nitro‐15N)‐1,3,5‐hexahydrotriazine, RDX‐(15NO2)3, by nitrolysis of 1,3,5‐triacetyl‐1,3,5‐hexahydrotriazine is described. A method for recovery of the nitrogen‐15 labelled nitric acid not consumed in the nitrolysis is also provided.
Synthesis of malondialdehyde‐1‐2H and malondialdehyde‐1,3‐2H2
Authors: Basu Ashis K. , Marnett Lawrence J.
Published: October 2006

Two synthetic routes for deuterium labelling of 1,1,3,3‐tetraethoxypropane, the precursor of the ubiquitous natural compound malondialdehyde, are described. In one scheme, deuterium is incorporated in ethyl vinyl ether by metalation with t‐butyllithium followed by quenching with 2H2O. The conversion of the deuterated ether to monodeuterated tetraethoxypropane, however, proceeds with an overall yield of only ˜5%. As an alternative route, we have metalated the bis‐1,3‐propylene dithioacetal of malondialdehyde which undergoes excellent deuterium incorporation (92%). In addition, the latter method allows isotopic labelling of either one or two deuterium(s) /molecule. Hydrolysis of the deuterated dithioacetal to the corresponding tetraethoxypropane can be best effected by refluxing with HgO(red) /HgCl2/BF3. etherate in the presence of CH(OC2H5)3/C2H5OH. The overall yield of the method is 48%.
Synthesis of [4,6‐13C]nicotinic acid
Authors: Barber Jill
Published: October 2006

A simple, economic synthesis of [4,6‐13C]nicotinic acid is described.
A remote system for the routine production of oxygen‐15 radiopharmaceuticals
Authors: Welch Michael J. , Kilbourn Michael R.
Published: October 2006

The details of the construction and operation of a remote, automated system for the production of oxygen‐15 labeled radiopharmaceuticals are described. This system routinely provides oxygen‐15 labeled oxygen, carbon monoxide, and water directly to the PET imaging facility, in quantities and purities suitable for human studies.
Synthesis of DL‐[2‐13C, 15N]aspartic acid
Authors: Baxter Robert L. , Abbot Elaine M.
Published: October 2006

A synthesis of the title compound from [13C]paraformaldehyde and [15N]ammonium chloride via ethyl 2‐(1, 3‐[2‐13C]dithianyl) acetate 3a is described. Ethyl[3‐13C]3‐oxopropanoate derived in situ from 3a was converted by a stepwise strecker procedure to DL‐[2‐13C, 15N]aspartic acid 7a.
Synthesis of [2‐13C]quinoline and [3‐13C]quinoline
Authors: Baldwin Michael A. , Langley G. John
Published: October 2006

[2‐13C]Quinoline and [3‐13C]quinoline were synthesised by a five‐step process starting from isatin. Acetylation of isatin with acetyl chloride labelled in either the 1‐ or 2‐position, was followed by the pfitzinger reaction to give 2‐hydroxy‐4‐quinoline carboxylic acid labelled in the 2‐or 3‐position. Decarboxylation by pyrolysis was followed by chlorination and reduction to the labelled quinolines. The overall yield was approximately 20%
Synthesis of15N‐labelled urea and methylenediurea
Authors: Murray Thomas P. , Austin Ernest R. , Howard Robert G. , Jones G. T.
Published: October 2006

A new technique was developed for the large‐scale synthesis of15N‐labelled urea at low enrichment levels. The synthesis is based on nucleophilic displacement of the phenoxide ion from phenyl carbonate and uses anhydrous ammonia as the nucleophile. In previous reports a copper catalyst was used; however, in this study it was found that the copper resulted in product decomposition and tar formation, which makes product purification difficult. A novel set of reaction conditions was developed: no catalyst was used, and no product decomposition or tar formation occurred. The reaction product was easily purified, and consistently high yields of15N‐labelled urea were obtained.

15N‐labelled methylenediurea was prepared by the dilute solution reaction of formalin with15N‐labelled urea. The methodology developed for the reclamation of unreacted urea resulted in minimum loss of labelled urea.

High performance liquid chromatography has been used to determine the chemical purity of both urea and methylenediurea.
Synthesis of tritium and carbon‐14 labeled timefurone
Authors: Hsi Richard S. P. , Gammill Ronald B. , Daniels Edward G.
Published: October 2006

Timefurone (1), a methyl thioether analogue of khellin (2), was labeled with tritium at the C‐2 position and with carbon‐14 at the C‐5 position for conducting in vivo biotransformation studies with 1. Tritium labeled 1 was prepared by lithiating and tritiating a silyllated derivative of khellinone (3) at C‐2, followed by converting the labeled khellinone into 1. Carbon‐14 labeled 1 was obtained by first dismantling the pyrone ring of khellin, followed by reconstruction of the ring with incorporation of carbon‐14 into the carbonyl position.
Synthesis of L‐[1‐13C]isoleucine via amidocarbonylation
Authors: Yuan Sun‐Shine , Ajami Alfred M.
Published: October 2006

Cobalt catalyzed amidocarbonylation of 2‐methylbutanal with [13C]carbon monoxide gave N‐acetyl‐D, L‐[1‐13C]alloisoleucine and N‐acetyl‐D, L‐[1‐13C]alloisoleucine and N‐acetyl‐D, L‐[1‐13C]isoleucine. The former was separated by crystallization from acetone and resolved by renal acylase I to give L‐[1‐13C]alloisoleucine (1) and N‐acetyl‐D‐[1‐13C]alloisoleucine (2). Then 2 was epimerized and resolved to produce L‐[1‐13C]isoleucine (3). The crystallization mother liquor was selectively resolved by Aspergillus acylase to yield 3.
Synthesis of α,β‐DI[3H]–2–fluoro–L–histidine
Authors: Takahashi Kazuyuki , Kirk Kenneth L. , Cohen Louis A.
Published: October 2006

The potent antimetabolite, 2‐fluoro‐L‐histidine, has been synthesized from 2‐fluoroimidazole with nonexchangeable 3H labeling in the side chain. 2‐Fluoro‐4‐iodoimidazole was N‐tritylated, was subjected to metal‐halogen exchange with n‐butyllithium, and the carbanion formylated with DMF. The imidazole‐4‐aldehyde was condensed with hippuric acid, the azlactone was solvolyzed with methanol, and the trityl group was removed by selective reduction with PtS2. The resultinq 2‐fluoro‐α‐benzamidoacrylic ester was reduced with tritium gas and the blocking groups were removed successively with base and with acylase I to produce the L‐enantiomer of the free amino acid analogue.
Synthesis of 2,4‐diphenyl‐5‐ethoxycarbonyl‐1‐heptadeuterated isopropyl‐2‐imidazoline
Authors: Bonnier M. , Marsura A. , Luu‐Duc C.
Published: October 2006

The synthesis of the title compound is described from heptadeuterated isopropyl alcohol in six steps. Overall yield obtained was 6%.
Syntheses of protoporphyrin‐IX regioselectively carbon‐13 labelled at the alpha‐vinyl carbons
Authors: Smith Kevin M. , Fujinari Eugene M.
Published: October 2006

A method for transformation of readily available beta‐vinyl 99% carbon‐13 enriched derivatives of protoporphyrin‐IX dimethyl ester (3‐5) into the less accessible alpha‐vinyl labelled isomers (6‐8) is described. The procedure involves thallium(III) promoted vinyl carbon rearrangement, and proceeds through 2,2‐dimethoxyethyl (e.g. 10), formylmethyl (e.g. 11), 2‐hydroxyethyl (e.g. 12) and 2‐chloroethyl (e.g. 13) porphyrins; the rearranged vinyl groups are regenerated from 2‐chloroethyl in the last step by treatment with base. No evidence of vinyl carbon scrambling in the sequence is observed, and spectroscopie data of the products are given.
Syntheses of 2‐(diacetoxymethyl‐14C)‐5‐nitrofuran and carbon‐14 labeled nitrofurazone
Authors: Duclos Richard I , Hoener Betty‐Ann
Published: October 2006

A new method for the microscale syntheses of carbon‐14 labeled 5‐nitrofuran derivatives of high specific activities was developed. Ethyl 2‐furancarboxylate‐carboxy‐14C (3) was prepared in an improved yield from Ba14CO3. 2‐Furancarboxaldehyde‐formyl‐14C (5) was prepared by reduction of the ester 3 followed by γ‐MnO2 oxidation of 2‐(hydroxymethyl‐14C)furan (4). 2‐(Diacetoxymethyl‐14C)‐5‐nitrofuran (7), an immediate precursor of many radiolabeled 5‐nitrofuran drugs, was prepared in a new two‐reaction one‐flask procedure from 2‐furancarboxaldehyde‐formyl‐14C (5) in 7.3% overall radiochemical yield from Ba14CO3. Carbon‐14 labeled nitrofurazone (8) was then prepared from 7.
Methodes Generales de Syntheses de Composes Lineaires ω‐Trideuteries
Authors: Bouloussa O. , Denhez J. P. , Dizabo P.
Published: October 2006

Nous proposons dans ce travail deux méthodes générales de synthése de composés trideutériés sur le méthyle terminal d'une chaine aliphatique. Dans les deux cas. l'hydrolyse de l'un des groupements esters constitue la premiére étape du schéa réactionnel. L'acide ester obtenu est transformé i) en aldéhyde ester; une réaction de Wittig conduit au vinyl ester. Le groupement ester est réduit d'abord en alcool 1‐2H2, puis par l'intermédiaire du mésylate en ω‐2H3 l‐alcene. L'oxydation de ce composé donne l'acide ω‐2H3. ii) en alcool ester. La fonction alcool est protégée par le dihydropyranne et le groupement ester est traité comme ci‐dessus. On obtient ainsi l'alcool ω‐2H3.
The synthesis of deuterium labelled metabolites of warfarin and phenprocoumon
Authors: Heimark L. D. , Toon S. , Low L. K. , Swinney D. C. , Trager W. F.
Published: October 2006

The synthesis of deuterium labelled 4′‐,6‐,7‐ and 8‐hydroxy metabolites of warfarin and phenprocoumon is described. The pentadeuterio labelled 6‐,7‐ and 8‐hydroxyphenprocoumons were prepared via alkylation of the respective 6‐, 7‐ and 8‐methoxy‐4‐hydroxycoumarins with 1‐(phenyl‐d5)‐1‐bromopropane and subaequent cleavage of the methyl protecting group with boron tribromide. The synthesis of 1‐(pentadeuteriophenyl)‐1‐bromopropane and the 6‐, 7‐ and 8‐methoxy‐4‐hydroxy‐coumarins are also presented. The pentadeuterio labelled 6‐, 7‐ and 8‐hydroxy‐warfarins were obtained by reaction of 4‐(phenyl‐d5)‐3‐buten‐2‐one with the respective 6‐, 7‐ and 8‐hydroxy‐4‐hydroxycoumarins in methanol followed by hydrolysis of the intermediate cyclic methyl ketals in aqueous acid. 4‐Hydroxycoumarin‐5,6,7,8‐d4, prepared from phenyl‐d6 and tetradeuteriomalonic acid, was reacted with 1‐(p‐hydroxyphenyl)‐1‐propanol and 4‐(p‐hydroxyphenyl)‐3‐buten‐2‐one to yield labelled 4′‐hydroxyphenprocoumon and 4′‐hydroxywarfarin respectively.
Synthesis of deuterium labelled ibuprofen
Authors: Capponi Vincent J. , Halstead Gordon W. , Theis Donald L.
Published: October 2006

The preparations of [ar‐2H4]‐ibuprofen and [ar, 3,3,3‐2H7]‐ibuprofen are described. The deuterium was incorporated into the aromatic ring of [ar‐2H4]‐ibuprofen which is a metabolically stable Position. [ar,3,3,3‐2H7]‐ibuprofen was synthesized by the same route using [2H3]‐CH3I instead of CH3I for use as a GC/MS internal standard in stable isotope labelled bioavailability studies.
Synthesis of deuterated eicosanoids
Authors: Meese Claus O.
Published: October 2006

Deuterated lipoxygenase and cyclooxygenase derivatives of eicosatetraenoic acid (arachidonic acid) and their metabolites are indispensable tools for organic trace analysis, biomedical studies, and mechanistic investigations on the corresponding endogenous (unlabelled) eicosanoids. Methods for the preparation of deuterated eicosanoids are reviewed.
Synthesis of 2,5‐dihydroxy[carboxy‐14C]benzoic acid for electrochemical protein modification
Authors: John Varghese , Vennerstrom Jonathan L. , Holmes Thomas J.
Published: October 2006

The synthesis of 2,5‐dihydroxy[carboxy‐14C]benzoic acid (gentisic acid) is described. The procedure utilized [carboxy‐14C]salicylic acid as a starting material. Salicylic acid was converted to gentisic acid using potassium persulfate hydroxylation. The mixture of hydroxylation products in this reaction was easily separated by UV‐visualized quartz column chromatography to obtain the desired isomer in high purity (overall yield of 38%). This procedure may be used for micro and semimicro preparation of the title compound.
Synthesis of carbon‐14‐labeled sodium palmoxirate and its coenzyme a ester
Authors: Weaner Larry E. , Hoerr David C.
Published: October 2006

Synthetic procedures for the preparation of carbon‐14‐labeled sodium palmoxirate (TDGA), labeled either in the carboxyl position or in the tetradecyl hydrocarbon chain, are described. In addition, the synthesis of the coenzyme A ester of TDGA‐14C with a specific activity of 51 mCi/mmol is reported. The coenzyme A ester was prepared by formation of the acyl chloride with oxalyl chloride followed by reaction with coenzyme A (CoA) in a borate‐buffered tetrahydrofuran solution. Purification methods and analytical and stability data are reported for the compounds.
Synthesis of tritium‐labelled cembrene‐A
Authors: Singh Ambarish K. , Prestwich Glenn D.
Published: October 2006

The synthesis of [16‐3H]‐cembrene‐A from unlabelled cembrene‐A is achieved in four steps via selective hydroboration‐oxidation of the isopropenyl double bond, borotritide reduction of the 16‐aldehyde, and o‐nitroselenoxide elimination to regenerate the labelled olefin. This sequence is of general utility in labelling polyisoprenoid hydrocarbons for metabolic studies. Cembrene‐A is a putative intermediate in the conversion of geranylgeranyl pyrophosphate to the polycyclic trinervitane and kempane diterpenes of nasute termite soldiers.
Synthesis of tritium labeled pramiracetam (CI‐879; N‐[2‐[bis(1‐methylethyl)amino]ethyl]‐2‐oxo‐1‐pyrrolidineacetamide)
Authors: Dodd J. H. , Hershenson F. M. , Hicks J. L. , Butler D. E. , Lewis E. P. , Huang C. C.
Published: October 2006

Pramiracetam (CI‐879; N‐[2[bis(1‐methylethyl)amino]ethyl]‐2‐oxo‐1‐pyrrolidineacetamide) was radiolabeled with tritium. Catalytic reduction of ethyl 2,5‐dihydro‐2‐oxo‐lH‐pyrrole‐1‐acetate in the presence of Pd/C gave ethyl 2‐oxo‐1‐[3,4‐3H]pyrrolidineacetate. Treatment of the tritiated ester with N,N‐bis(1‐methylethyl)‐1,2‐ethanediamine gave pramiracetam, which was subsequently converted to the corresponding sulfate salt.
Synthesis of 1,1,3,3‐(2h4)‐4‐hydroxydebrisoquine sulphate
Authors: Meese Claus O.
Published: October 2006

An efficient synthesis of the analytically useful title compound 2c (1,1,3,3‐(2H4)‐4‐hydroxydebrisoquine sulphate), utilizing a two‐step deuteration(1H/2H exchange of 3‐nitromethylphthalide,4, and LiAl2H4 reduction of 3,3‐(2H2)‐4‐hydroxy‐1,2,3,4‐tetrahydro‐isoquinolin‐1‐one, 6), is described.
Preparation of N.C.A. [17‐18F]‐fluoroheptadecanoic acid in high yields via aminopolyether supported, nucleophilic fluorination
Authors: Coenen Heinrich Hubert , Schüller Manfred , Stöcklin Gerhard , Klatte Bernd , Knöchel Arndt
Published: October 2006

A macrocyclic aminopolyether (Kryptofix®2.2.2.) supported labelling method for the preparation of n.c.a. [17‐18F]‐ fluoroheptadecanoic acid is described. The equimolar complex of potassium carbonate and the aminopolyether ([2.2.2./K]+2;CO32‐) is used to provide 18F‐fluoride of high nucleophilicity in a homogeneous solution of acetonitrile. Nucleophilic 18F‐for‐Br substitution in the methylester of 17‐bromoheptadecanoic acid is accomplished with radiochemical yields of 94 + 3%. Subsequent quantitative ester hydrolysis with KOH leads to a simple “one pot” procedure. Minimization of reagent concentrations allows a direct isolation of the product from the reaction mixture by means of reverse phase HPLC. The corrected radiochemical yield of high activity level routine production is 82 + 2% after 90 minutes of synthesis time. The specific activity is > 10,000 Ci/mmol.
Preparation of no‐carrier‐added 4‐[131i]iodoantipyrine using chloramine‐T
Authors: Boothe Thomas E. , Finn Ronald D. , Vora Manhar M. , Kothari J Paresh , Emran Ali M.
Published: October 2006

The blood flow reagent 4‐iodoantipyrine, labelled with 131I or 125I, was prepared by allowing aqueous antipyrine to react with either no‐carrier‐added 131I−I or 125I−I in the presence of chloramine‐T. Purification of 4‐[131I]iodoantipyrine was performed by reversed‐phase liquid chromatography and resulted in a 99 ± 1% radiochemically pure product in an overall 90% yield. The use of iodogen for oxidation of the radioiodine was also investigated.
Preparation of 18O‐bilabelled carboxylic acids: Cinnahic and phenylpropiolic acids via styrylisoxazoles
Authors: Baracchi A , Chimichi S , De Sio F. , Donati D , Nesi R , Sartifantoni P. , Torroba T
Published: October 2006

3‐Phenyl‐2‐propenoic (cinnamic) and 3‐ [2H5] ‐phenyl‐2‐ propenoic 80O‐bilabelled acids (2c,d) are prepared via alkaline hydrolysis of styrylisoxazoles (1a,b). The same reaction carried out on the vic‐dibromocompounds (3a,b) gave the 3‐phenyl‐2‐propynoic (phenylpropiolic) and 3‐[2H5]‐Phenyl‐2‐propynoic 18O‐bilabelled acids (4c,d), respectively.
Synthesis of tritiated functionalized congeners of 1.3‐dipropylxanthine having high affinity at adenosine receptors
Authors: Jacobson Kenneth A. , Ukena Dieter , Daly John W. , Kirk Kenneth L.
Published: October 2006

Two potent ligands for adenosine receptors have been synthesized with non‐exchangeable 3H labeling to high specific activity. Both are adenosine antagonists. one a carboxylic acid congener, 1, and the other an amino congener. 2. and are structurally related to 1,3‐dipropyl‐8‐phenylxanthine. The label was introduced at four positions in the n‐propyl groups through catalytic reduction of 1,3‐diallyl precursors. Due to favorable aqueous solubility. high potency and selectivity. these ligands are expected to be suitable for competitive binding assays and autoradiography.
Preparation of (10R,s‐[10‐3H]juvenile hormone III and (10R,S,11S,R)‐[10‐3H]juvenile hormone 0; conversion of [10‐3H] juvenile hormone III to methyl (2E,6E)[10‐3H]Farnesoate and (2E 6E)‐ [10‐3H] farnesol
Authors: Baker Fred. C. , Schooley David A.
Published: October 2006

Samples of racemic [10‐3H]juvenile hormone III (methyl (2E,6E)‐10,11‐epoxy‐ 3,7,11‐trimethyl‐2,6‐dodecadienoate) and [10‐3H]juvenile hormone 0 (methyl (2E,6E,10cis)‐3,7‐diethyl‐10,11‐epoxy‐11‐methyl‐2,6‐tridecadienoate) were prepared by NaB3H4 reduction of the corresponding 11‐chloro‐10‐oxo ( “chloroketone” ) precursors to their respective [10‐3H]chlorohydrins, followed by treatment of the latter with potassium carbonate in methanol. [10‐3H]Juvenile hormone III was converted to methyl [10‐3H]farnesoate (methyl (2E,6E)‐3,7,11‐trimethyl‐ 2,6,10‐dodecatrienoate) by reduction with sodium iodide and zinc in acetic acid‐sodium acetate. Further reduction of methyl [10‐3H]farnesoate with diisobutyl aluminum hydride afforded a sample of [10‐3H]farnesol ((2E,6E)‐3,7,11‐trimethyl‐2,6,10‐dodecatrien‐1‐ol).
Preparation of N.C.A. [18F]‐CH2BrF via aminopolyether supported nucleophilic substitution
Authors: Coenen Heinrich Hubert , Colosimo Marcello , Schüller Manfred , Stöcklin Gerhard
Published: October 2006

A complex of the macrocyclic aminopolyether Kryptofix® 2.2.2. and potassium carbonate was used to synthesize [18F]‐CH2BrF from dibromomethane. At the no‐carrier‐added level the nucleophilic 18F‐for‐Br exchange gives rise to a corrected radiochemical yield up to 62%.
Synthesis of 14C‐labelled leukotriene receptor antagonists: 5‐Substituted‐4,6‐dithianonanedioic acid derivatives
Authors: Kuot George Y. , Dewey Richard H. , Newton John F. , Perchonock Carl D. , McCarthy Mary E.
Published: October 2006

Two 14C‐labelled leukotriene receptor antagonists were prepared from two aryl bromides and potassium [14C]cyanide. Potassium cyanide was converted to copper(I) [14C]cyanide and was subsequently used to displace the bromine atom from two aryl bromides, 2‐dodecylbromobenzene and 2‐(8‐phenyloctyl)bromobenzene. The resulting nitriles were reduced to aldehydes with diisobutylaluminum hydride and the aldehydes were reacted with 3‐mercaptopropionic acid to give 5‐(2‐dodecylphenyl)‐4,6‐dithianonanedioic acid (14C‐SK&F 102081) and 5‐[2‐(8‐phenyloctyl)phenyl]‐4,6‐dithianonanedioic acid (14C‐SK&F 102922), respectively. These products were snythesized in about 30% overall yield with radiochemical purity of greater than 95%. Their structures were assigned based on the analytical data of the corresponding nonradiolabelled compounds obtained from the nonradioactive preparations.
Synthesis and biodistribution of radioiodinated nicotine analogs
Authors: Chan S. M. , Basmadjian G. P. , Sadek S. A. , Magarian R. A. , Grunder J. R. , Marten D. F.
Published: October 2006

Four 125I‐labelled nicotine analogs were synthesized: 3‐(methylpropylaminomethyl)‐, 3‐(diethylaminomethyl)‐, 3‐(isopropylaminomethyl)‐, and 3‐(diisopropylaminomethyl)‐5‐[125I]‐iodopyridines. 5‐Bromonicotinic acid was acylated with thionyl chloride and then reacted with the appropriate primary and secondary amines to give the corresponding amides which were reduced with diborane to the desirable amines. Radioiodination was done by halogen exchange. Biodistribution studies in rats, showed that all four labelled compounds were rapidly taken up by the brain and the adrenal gland. This was followed by rapid washout of the compounds from these orrans. The most promising of these compounds, 3‐(diisopropylaminomethyl)‐5‐[125I]‐iodopyridine, showed a brain‐to‐blood ratio of 6.0:1 and an adrenal‐to‐blood ratio of 35.9:1 at 2 minutes post administration. In vitro correlation studies showed that brain uptake of these compounds depends on both protein binding and lipophilicity, whereas adrenal uptake depends only on lipophilicity.
Synthesis of 2,6‐dimethyl‐l,2,3,4‐tetrahydronaphthalene‐4‐13C and 2,6‐dimethylnaphthalene‐413C
Authors: Bymaster D. L. , Pickering R. E. , Dobbs T. K. , Eisenbraun E. J.
Published: October 2006

The synthesis of specifically labeled β,4‐dimethyl‐benz‐enebutanoic acid‐1‐13C, 3,4‐dimethyl‐ 1,2,3,4‐tetrahydronaphthalene‐4‐13C and 2,6‐dimethylnaphthalene‐4‐13C from Diethyl 2‐(4‐methylphenyl)‐2‐methylpropanediate is described.
One pot synthesis of sodium 14C‐formate
Authors: Parnes Howard , Shelton Emma
Published: October 2006

A one pot synthesis of sodium 14C‐fonmate by reduction of 14CO2 with NaBH(OMe)3 in THF solution is described. This process is suitable for large scale, high specific activity preparations.
Synthesis of deuterium labelled thioridazine
Authors: Mohammad T. , Midha K. K. , Hawes E. M.
Published: October 2006

A seven step synthetic route to (±)‐10‐[2‐(1‐methyl‐2‐piperidinyl)ethyl]‐2‐methylthio‐10H‐phenothiazine (thioridazine) was developed starting from racemic ethyl 1‐methyl‐2‐piperidinecarboxylate. The lithium aluminum deuteride reduction of the starting and homologous esters allowed the incorporation of deuterium in the 1‐and/or 2‐position(s) of the ethyl side chain of thioridazine. The isotopic purity of the tetradeuterated and two dideuterated products was greater than 99%.
Syntheses of |6‐2h|‐indole, |6‐2h|‐gramine and |6‐3h|‐gramine
Authors: Ghini A. A. , Burton G. , Gros E. G.
Published: October 2006

The title compounds were obtained from the corresponding 6‐bromo derivatives by conversion to the 1,6‐dilithio‐compounds followed by treatment with deuteriated or tritiated water and exchange of the 1‐deuterium or tritium with water.
Synthesis of 7‐[α‐(2‐aminothiazol‐4‐yl)‐α‐(z)‐methoximinoacetamido]‐3‐(1‐[14C]methylpyrrolidinio)‐methyl‐3‐cephem‐4‐carboxylate sulfate
Authors: Swigor J. E. , Pittman K. K.
Published: October 2006

The synthesis of the title compound (6) is described. The reaction of sodium [14C] formate with acetyl chloride produced the mixed anhydride. Treatment with pyrrolidine gave the N‐formyl compound in a 4 to 1 ratio with the N‐acetyl compound.1 Separation and reduction with lithium aluminum hydride gave N‐[14C]methylpyrrolidine2. Reaction with 7‐[α‐(2‐triphenylmethylaminothiazol‐4‐yl)‐α‐(z)‐methoximinoacetamido]‐1‐oxo‐3‐iodomethyl‐3‐cephem‐4‐carboxylate diphenylmethyl ester introduced the label into the cephalosporin. Treatment with acetyl chloride converted the sulfoxide to the sulfide. Formic acid at 39°C removed the protecting groups and treatment with 4N sulfuric acid produced the title compound as a sulfate salt.
Synthesis of 1‐[14C]methyl‐1H‐tetrazole‐5‐thiol([14C]NMTT) and [NMTT‐[14C]]latamoxef
Authors: Nagasaki T. , Katsuyama Y. , Yoshioka M.
Published: October 2006

The title compounds were prepared for metabolic studies, with the 14C labelling being made at methyl of the 1‐methyl‐1H‐tetrazol‐5‐ylthio (NMTT) group in overall radiochemical yields of 26% and 22% based on barium [14C]carbonate, respectively.
Preparation of 2H‐ and 13C‐labelled precursors of 2‐hydroxy‐1,3‐butadiene
Authors: Tureček František
Published: October 2006

2‐exo‐Vinylbicyclo[2.2.1]hept‐5‐en‐2‐ols, specifically labeled with 2H at C‐3 and in the vinyl group were prepared from bicyclo [2.2.1]hept‐5‐en‐2‐one in several steps. [4‐13C]Oct‐1‐en‐3‐one was prepared in five steps from 13CO2. These compounds serve as precursors for the preparation of specifically labeled neutral and ionized 2‐hydroxy‐1,3‐butadienes.
Synthesis of carbon‐14 labeled 4‐bromo‐2,7‐dimethoxy‐3H‐phenothiazin‐3‐one
Authors: Prakash S. R. , Ellsworth R. L. , Mertel H. E.
Published: October 2006

Two different syntheses of (5), one labeled with carbon‐14 in the quinonoid ring and the other in the phenyl ring are described. Treatment of p‐[U‐14C]benzoquinone with 2‐amino‐5‐methoxy benzenethiol yielded (7), which was methoxylated to provide a mixture of isomers (4a) and (8). Separation of isomers followed by bromination of (4a) gave (5a). Thiocyanation of p‐[U‐14C]anisidine provided (10), which was hydrolysed to give labeled aminothiol (3b); the latter was condensed with 2‐bromo‐6‐methoxy‐p‐benzoquinone to afford (5b).
Synthesis of 14C‐labelled 2‐aminopyridine
Authors: Lenoir H. H. C. , Janssen C. C. M.
Published: October 2006

2‐Aminopyridine is a versatile building block in the preparation of certain heterocycles such as imidazo[1,2‐a]‐pyridines, pyrido[1,2‐a]‐pyrimidin‐ones and substituted derivatives there‐of. 14C‐labelled 2‐aminopyridine was synthesized as follows: potassium‐[14C]cyanide (I) was reacted with epichlorohydrin (II) to give 3‐hydroxy‐[1,5‐14C2]pyridine (IV) which was then reductively dehalogenated to the 2,6‐14C2‐labelled title compound (V) in 36 % overall chemical and radio‐chemical yield, based upon I. The product was radiochemically pure (99.1 %) according to high‐performance liquid chromatography and thin‐layer chromatography, and had a specific activity of 9.06 mCi/mmol.
Synthesis of 4‐[2‐(DI‐n‐propylamino)ethyl]‐[2‐14C]‐2(3H)‐indolone
Authors: Heys J. Richard
Published: October 2006

4‐[2‐(Di‐n‐propylamino)ethyl]‐2(3H)‐indolone (1) labeled with 14C at C2 was prepared by a simple and efficient procedure involving carbonation of a stabilized benzyllithium species, followed by ring closure under hydrolytic conditions.
Microscale synthesis of high specific activity 3H‐nitroglycerin
Authors: Kawamoto J. J. , Brien J. J. , Marks G. G. , Nakatsu K.
Published: October 2006

The synthesis and purification of 3H‐nitroglycerin (glyceryl trinitrate, GTN) from commercially available 3H‐glycerol of high specific activity are described. The optimum microscale reaction conditions were defined. Purification of the product by thin‐layer chromatography produced 3H‐GTN with an overall molar yield of 65% and a radiochemical purity of 99.0%.
Crown ether catalyzed deuterium exchange in the synthesis of benzyl cyanides
Authors: Davis Bruce
Published: October 2006

Nucleophilic substitution of benzyl‐type chlorides with cyanide ion in deuterochloroform, deuteroacetonitrile or deuterobenzene catalyzed by 18‐crown‐6 results in the introduction of deuterium onto the benzyl carbon. Benzyl cyanides are labelled by refluxing with cyanide ion and crown ether in deutero solvent. Two such exchanges in deuterochloroform produced greater than 90% incorporation. Side‐chain labelled phenyl‐ethylamine, tryptamine and m‐ and p‐tyramine were synthesized in this way.
Synthesis of 11C‐pindolol
Authors: Prenant C. , Sastre J. , Crouzel C. , Syrota A.
Published: October 2006

A method is described by which 100 mCi of pindolol may be obtained from about 1.5 Ci 11CO2 in 30 minutes. The product is chromatographically pure, sterile and apyrogenic with a specific activity between 600 and 1000 mCi/μmole at the time of use.

The synthesis involves the preparation of 11C‐acetone followed by fixation of the isopropyl group on the precursor : 2 hydroxy‐3 (4‐indolyoxy) propylamine by formation of an imine, the reduction of the latter by sodium cyanoborohydride.
Synthesis of S‐benzyl‐[18O3]phosphorothioate and adenosine 5prime;‐[18O3]phosphate
Authors: Bethell Richard C. , Lowe Gordon
Published: October 2006

Several synthetic routes to the two title compounds are presented. S‐Benzyl‐[18O3]phosphorothioate was synthesised in 68% yield from phosphorus trichloride. Adenosine 5′‐[18O3]phosphate was synthesised in two steps from adenosine in 44% yield.
Synthese des Isomeres (E) et (Z) de la Phenylhydrazone De L'hexanal (noyau 14C ‐ U)
Authors: Do‐Cao‐Thang  , Nguyen‐Hoang‐Nam  , Chopard C. , Galey J. B. , Chottard J. C.
Published: October 2006

Synthesis and chromatographic separation of (E) and (Z) isomers of (ring‐U‐14C) hexanal phenylhydrazone 2 : (ring‐U‐14C) phenylhydrazine hydrochloride 1 was synthesized from labelled aniline hydrochloride, and purification was accomplished by reverse phase low pressure liquid chromatrography. The crude free base of 1 was condensed with hexanal to give a mixture of (E) and (Z) isomers of 2. The conditions for their separation by reverse phase HPLC were optimized on an analytical column and then used for the preparative work which was the most effective and fastest method.

Structure and configuration of (E) and (Z) isomers of (ring‐U‐14C) hexanal phenylhydrazone (SA = 13.3 mCi/mmol) were proven by 1H‐NMR and mass spectroscopy.
A simple procedure for the preparation of tritiated homovanillic acid
Authors: Keenan Roy W.
Published: October 2006

Homovanillic acid (4‐hydroxy‐3‐methoxyphenylacetic acid) was labeled with tritium by exchange reaction in tritiated water catalyzed by sulfuric acid. The product was obtained in good yield and specific activities sufficient be utilized in metabolic experiments. Reactions carried out under identical conditions, but in the presence of deuterated water gave a product in which all the aromatic hydrogens and those α ‐ to the carboxyl group were replaced with deuterium indicating that the tritium‐labeled homovanillic acid was labeled in these positions.
Oxidation of cystine to cysteic acid by bromine in 18O‐labelled water, evidence for a cyclic carboxylic‐sulfenic anhydride
Authors: White Robert H.
Published: October 2006

Oxidation by bromine of L‐cystine dissolved in acidified 18O‐enriched water (95 atom % 18O) led to the production of cysteic acid which contained two 18O atoms in the carboxylic acid protion and two 18O atoms in the sulfonic acid portion of the molecule. It is postulated that the incorporation of a single 16O into the sulfonic acid results from an intramolecular transfer of a carboxyl oxygen via a cyclic carboxylic‐sulfenic anhydride intermediate which is formed during the oxidation. The remaining carboxyl oxygen is postulated to exchange from either the cyclic anhydride or the free carboxylic acid during the reaction.
Synthesis of U‐14C‐labelled 5‐hydroxymethyl‐2‐furaldehyde
Authors: Germond J. J. , Arnaud M. M.
Published: October 2006

Uniformally 14C‐labelled 5‐hydroxymethyl‐2‐furaldehyde was synthesized by dehydration of D‐[U‐14C]fructose on an H+ ion exchange resin and a water isobutylmethyl ketone biphasic liquid reaction medium. The optimal reaction time was 45min, and after HPLC purification the radiochemical yield was 50%. The whole process took 2 hours.
Synthesis of carbon‐14 labeled CI‐926 and CI‐927, new antihypertensives
Authors: Hays Sheryl J.
Published: October 2006

3‐[4‐]4‐(3‐Methylphenyl)‐1‐piperazinyl[butyl]‐2,4‐imidazolinedione, CI‐926 (1), and 3‐[4‐4‐(3‐ethoxyphenyl)‐1‐piperazinyl]butylamino‐5,5‐dimethyl‐2‐cyclohexen‐1‐one, CI‐927 (2) are new antihypertensive agents which have been carbon‐14 labeled in three steps starting from ethylene‐14C2 oxide (5). The overall radiochemical yields for 1 and 2 were 69% and 66% respectively. The specific activity for both compounds was initially 22.6 mCi/mmol before final dilution.
Synthesis of tritium labeled O‐ethyl‐D‐tyrosine and phenylalanine
Authors: Landvatter Scott W. , Heys J. Richard , Senderoff Stephen G.
Published: October 2006

Two amino acids, t‐BOC‐O‐ethyl‐D‐tyrosine and t‐BOC‐phenylalanine, have been synthesized in tritium labeled form via exchange with tritium gas over catalyst on an unlabeled precursor and dehydrohalogenation on an iodinated precursor respectively. The tyrosine derivative has been obtained in specific activities of 4 ‐ 7 Ci/mmol; tritium NMR indicates that at least 80% of the tritium resides in the benzylic position of the molecule. The phenylalanine has been synthesized with a specific activity of greater than 35 Ci/mmol. Tritium NMR confirms specific tritium/iodine replacement in the position.
Synthesis of [Imidazolidinone‐2‐14C]Go 10213 (satranidazole, cibemid®)
Authors: Anjaneyulu B. , Nagarajan K.
Published: October 2006

For additional pharmacokinetic and metabolism studies in laboratory animals and in humans, Go 10213 was labelled with carbon‐14 located on the carbonyl carbon atom of the ethyleneurea ring (Ring B) of the molecule. [imidazolidinone‐2‐14C]Go 10213 having a specific activity of 6.06 μCi/mg (1.75 mCi/mmol) was synthesised starting with [14C]ethyleneurea in two steps.
Synthesis of 7‐chloro‐1,3,‐dihydro‐3‐hydroxy‐1‐methyl‐5‐phenyl‐2h‐1,4‐benzodiazepin‐2‐one‐2‐14c (2‐14C‐temazepam)
Authors: Dain Jeremy G.
Published: October 2006

Temazepam‐2‐14C, 7‐Chloro‐1,3,‐dihydro‐3‐hydroxy‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one‐2‐14C, was prepared in a five‐step synthesis. Chloroacetic‐1‐14C acid was converted to the acid chloride with thionyl chloride. The acid chloride was allowed to react with 2‐methylamino‐5‐chloro‐benzophenone to form the amide. The amide was reacted with hydroxylamine and directly cyclized to the benzodiazepine N‐oxide which was converted to the acetate with acetic anhydride. The acetate was hydrolyzed with concentrated sulfuric acid to give the final product (3.8% radiochemical yield at 52. mCi/mmol). This procedure provides temazepam with the radiolabel in a metabolically stable position.
Synthesis of methanol tritiated in the methyl group only
Authors: Dass Desmond V. , Dempsey Victor J. , Martin R. Wayne , Odell Allan L.
Published: October 2006

Methanol has been labelled with tritium in the methyl group, and the position of the label confirmed using Tritium N.M.R. spectrometry. The methanol was prepared by reacting tritium, hydrogen and carbon dioxide over a copper/zinc/chromium catalyst at a total pressure of 500 psi. Water was removed by microdistillation followed by preparative G.L.C. These procedures also removed tritium from the hydroxyl group of the methanol.
Synthesis of 2‐amino‐1,5‐dihydro‐1‐(methyl‐13C)‐4H‐imidazol‐4‐one‐5‐13C (creatinine‐13C2)
Authors: Cohen A. , Hertz H. H. , Schaffer R. , Welch M. M. , White E.
Published: October 2006

2‐Amino‐1,5‐dihydro‐1‐(methyl‐13c)‐4h‐imidazol‐4‐one‐5‐13c (creatinine‐13C2) (8) is synthesized as follows. Glycine‐2‐13c (1) is tosylated; the product (2) is treated with iodomethane‐13C; and the resultant doubly‐labeled product (3) is detosylated to yield sarcosine‐13C2 (4). Creatine‐13C2 (7) is obtained by treating 4 with 2‐methylisothiourea monohydriodide (5) or cyanamide (6). Dehydration of 7 under vacuum sublimation conditions gives 8.
New realistic approach of the kinetics in fast labelling procedures
Authors: Mertens J. , Callaerts A. , Vanryckeghem W.
Published: October 2006

A real kinetic approach of fast labelling reactions is obtained by introducing a corrected reaction time τ which takes into account the temperature rise process of the reaction solution. τ is obtained by transformation of transient temperature data to isothermal conditions at a preset temperature. Experimental data obtained for 123I‐radioiodination of ortho‐iodohippuric acid fit completely with the theory.
The preparation and characterization of [3H] histamine.2HCl at high specific activity1
Authors: Filer Crist N. , Ahern David G.
Published: October 2006

[3H] Histamine.2HCl will continue to play a key role in establishing the neurotransmitter status of histamine.2HCl. To more consistently achieve high specific activity in the preparation of the radioligand and incorporate as much tritium into the stable side chain positions as possible, we explored the use of alternative tritiation precursors. Imidazole 4‐acetonitrile (5) and 2,5‐diiodoimidazole‐4‐acetonitrile (6) were catalytically reduced with tritium gas and the radiolabeling specificity of the resulting [3H] histamine.2HCl produced was confirmed by 3H NMR.
A new synthesis and NMR‐spectroscopy of [15N‐, 5,4‐13C]‐aminolevulinic acid
Authors: Nitsche Bernhard , Köst Hans‐Peter , Cmiel Edmund , Schneider Siegfried
Published: October 2006

A new synthesis of [15N‐, 5,4‐ 13C]‐aminolevulinic acid (ALA) starting from amorphous 13C is described. NMR‐spectroscopic data (1H, 13C, 15N) of the product are presented.
Possible drugs labelled with 14C.IV.1 synthesis of D‐pheylalaninyl‐prolyl‐arginine aldehyde labelled in the guanidino group
Authors: Koltai E. , Bajusz S. , Széll E. , Zólyomi G.
Published: October 2006

α‐tert‐Butyloxycarbonyl‐ω‐benzyloxycarbonyl‐[guanido‐14C]arginine was prepared by reacting α‐tert‐butyloxycarbonyl‐ornithine with N‐benzyloxy‐carbonyl‐S‐methyl‐[14C]isothiourea, and it was transformed to D‐phenylalaninyl‐prolyl‐[guanido‐14C]arginine aldehyde, via ω‐benzyloxycarbonyl‐[guanido‐14C]‐arginine lactam.
Preparation of [22,23‐3H2]‐dihydroavermectin B1a of high specific activity
Authors: Toth G. , Kardos J. , Fodor A. , Sirokman F.
Published: October 2006

[22,23‐3H2]‐Dihydroavermectin B1a of 2.13 TBq/mmo1 (57.7 Ci/mmol) specific activity was derived from avermectin B1a by selective tritiation using Wilkinson's homogeneous catalyst. Data on binding affinity and nematotoxic activity of the title compound are reported.
Synthesis of specifically labeled (S)‐nicotine‐5‐3H and (S)‐cotinine‐5‐3H BY carrier free tritiolysis of the corresponding 5‐bromo derivatives
Authors: Shigenaga Mark K. , Jacob Peyton , Trevor Anthony , Castagnoli Neal , Benowitz Neal
Published: October 2006

The synthesis of high specific activity tritium labeled (S)‐nicotine and (S)‐cotinine has been achieved. (S)‐5‐Bromonornicotine of high enantiomeric purity was converted to the corresponding (S)‐5‐bromonicotine by reductive amination with formaldehyde and sodium borohydride. Tritiolysis of this intermediate with carrier free tritium in the presence of triethylamine using 10% Pd/C catalyst provided (S)‐nicotine‐5‐ H with a specific activity of 32 Ci/mmol in ethanol solvent and 28 Ci/mmol in tetrahydrofuran solvent. Similarly, tritiation of (S)‐5‐bromocotinine, obtained by oxidation of (S)‐5‐bromocotinine, obtained by oxidation of (S)‐5‐bromonicotine with bromine followed by reduction of the intermediate (S)‐3′, 3′, 5‐tribromonicotine with zinc dust, yielded the corresponding (S)‐cotinine‐5‐ H (22.8 Ci/mmol). All reactions proceeded in good to excellent yields.
Catalytic tritiation and 3H NMR spectroscopy of complex organic mixtures ‐ application to engine oil basestocks
Authors: Carroll Leonor , Jones John R. , Shore Philip R.
Published: October 2006

Several catalytic hydrogen‐tritium exchange procedures have been investigated in order to accomplish uniform and random incorporation of tritium into the diverse organic components present in two engine oil basestocks. The most successful procedure involved the use of Raney nickel and tritiated water at elevated temperatures. Comparative proton and tritium nuclear magnetic resonance spectroscopy shows that the incorporated tritium was representative of the organic components present in the basestocks. Comparative gas‐ and radio‐gas chromatography studies provided supplementary information. These investigations demonstrate that engine oils can be satisfactorily labelled with tritium for studies of engine oil consumption.
Synthesis of 3H‐labelled levamisole
Authors: Thijssen J. J. A. , Knaeps A. A. , Verluyten W. W. M. , Heykants J. J. P. , Janssen C. C. M.
Published: October 2006

Levamisole, the levo isomer of tetramisole, is a potent anthelmintic also showing immunotropic properties. Renewed interest in the latter domain necessitated the synthesis of specifically 3H‐labelled levamisole of high specific activity.

Racemic 1‐(2‐bromophenyl)‐1,2‐ethane diamine dihydrochloride (V) was obtained via bromination of 1‐(2‐bromophenyl)ethanone (I), followed by reaction with 2,5‐pyrrolidinedione, Leuckart amination and hydrolysis. The racemate was then resolved by successive salt formation with (S)‐(‐) and (R)‐(+) tartaric acid. The liberated (S)‐(+)‐base of VI was dehalogerated with approximately 30 Ci of tritium gas and immediately ring‐closed with carbon disulfide to VIII. The HPLC‐purified material was finally cyclized with 1,2‐dibromo ethane to (S)‐(‐)‐2,3,5,6‐tetrahydro‐6‐[2‐T]phenyl‐imidazo‐(2,1‐b)‐thiazole IX and the isomerically ringclosed (S)‐2,3,5,6‐tetrahydro‐5‐[2‐T] phenyl‐imidazo‐(2,1‐b)‐thiazole X, of which levamisole IX was isolated via HPLC. The radiochemical yield over the cyclization steps was 28.2 %, the specific activity was 10.82 Ci/mmol, and the product was 99.9 % HPLC pure.
Synthesis of 14C‐labeled benzofurano[2,3‐b] benzopyran‐6‐one and its 4‐hydroxycoumarin derivative
Authors: Chubachi Mitsuo , Kawano Eiko
Published: October 2006

2‐Isopropyl‐8,9‐dimethoxy‐benzofurano [2,3‐b]furo[2,3‐h] [1] [11‐14C]benzopyran‐6‐one (IVb) and 3‐(2‐hydroxy‐4,5‐dimethoxyphenyl)‐4‐hydroxy‐5′‐isopropylfurano[2′,3′:7,8] [2‐14C]coumarin(Vb) were prepared from isorotenone (Ib) for use in metabolic and other studies. Deoxybenzoin derivative (IIb), obtained from isorotenone, was reacted with ethyl [14C] formate in the presence of sodium to give the corresponding [2‐14C]‐2′‐hydroxyisoflavone (IIIb), which was transformed into the 14C‐labeled benzofurano [2,3‐b]furo[2,3‐h]benzopyran‐6‐one compound (IVb) by the subsequent oxidative cyclization with selenium dioxide. Hydrolysis of compound IVb in alkaline media gave 14C‐labeled 4‐hydroxycoumarin (Vb).
Tritium labelled compounds of high specific activity III. Trifluoperazine
Authors: Zólyomi Gábor
Published: October 2006

Trifluoperazine labelled with tritium at a specific activity of 3.15 TBq/mmol was prepared by methylation of N‐desmethyltrifluoperazine with no‐carrier added [3H]methyl iodide. An improved method for preparation of the precursor is also described.
Synthesis of 7‐(4′‐fluoro‐3,3′,5‐trimethyl[1,1′‐biphenyl]‐2‐YL)‐3‐hydroxy‐5‐OXO‐5‐13C‐heptanoic acid and trans‐6‐[2‐(4′‐fluoro −3,3′,5‐trimethyl[1,1′‐biphenyl]‐2‐YL)ethyl]‐3,4,5,6‐tetrahydro‐6‐13C‐4‐hydroxy‐2H‐pyran‐2‐one
Authors: Stokker Gerald E.
Published: October 2006

The title compounds are potent HMG‐CoA reductase inhibitors. A 13C‐label was introduced into these compounds to permit probing of their interaction with HMG‐CoA reductase by 13C NMR techniques in the presence and absence of added NADPH.