bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorine‐18 labelling of lower fatty acid esters by heterogeneous exchange on gas chromatographic columns
Authors: Karim H. M. A. , Stöcklin G.
Published: October 2006

Fluorine‐18 produced via the reaction chain 6Li(n,α)t, 16O(t,n) 18F by reactor irradiation of Li2CO3 was directly recovered in carrier‐free form with a 90% yield by repeated extractions with water. A simple apparatus was used for simultaneous extraction and fast loading of an exchange resin with 18F. Dowex 1×4 in the acetate form was found to be best suited for a gas phase 18F‐for‐Br exchange in α‐bromofatty acid esters. The 18F‐loaded exchange resin was brought into a gas chromatographic column followed by an analytical column for the separation of the 18F‐labelled product from the unchanged bromine compound. The dynamic technique combines synthesis and purification and allows a fast and carrier‐free production of 18F‐α‐fluorofatty acid esters with boiling points up to about 300 °C. α‐fluoroacetic acid ethyl ester and α‐fluorovaleric acid methyl ester have been labelled carrier‐free with yields of 64% (at 170 °C) and 39% (at 190 °C), respectively. Kinetic studies on the yield determining factors have also been carried out.
Preparation De Thiazolidines Deuteriees En Positions 2,3,4 et 5
Authors: Guiliano Michel , Mille Gilbert , Chouteau Jacques , Larice Jean‐Louis , Roggero Jean‐Pierre
Published: October 2006

Two methods of synthesis of thiazolidinic cycle without substituent have been tested. For the classic cysteamine‐formaldehyde reaction we have shown that it was possible to obtain thiazolidine without passing through a chlorydrate intermediate (yield 50–60%). For Bestian's method (ethyleneimine‐formaldehyde reaction followed by H2S saturation), we have generalized a mode of operation which was applied up to now to obtain thiazolidine substituted in position‐2 only.

It's with the last method that we have prepared the 2,2 d2 thiazolidine, the 4,4,5,5 d4 thiazolidine and the 2,2,4,4,5,5 d6 thiazolidine. (Rating of deuteration upper than 95%).

By exchange with with D2O in acid medium we have prepared the 2,2,3 d3 thiazolidine. (Rating of deuteration on nitrogen atom: 97%).
Tritiation of low molecular weight alkanes and alkenes by self‐radiation induced exchange with HTO
Authors: Long Mervyn A. , Garnett John L. , Meakin Christopher P.
Published: October 2006

The tritiation of a range of low molecular weight alkanes and alkenes has been investigated by self‐radiation induced exchange with HTO at room temperature and 115°. By comparison with the Wilzbach T2 gas exposure procedure, the HTO method yields less byproducts and radiochemical purification of the parent compound is facilitated. With alkenes, saturation of the double bond is a competing process in the HTO procedure, however the significance of this side reaction decreases with increasing temperature of exchange. The HTO technique is shown to be suitable for tritiating a wide range of hydrocarbons to medium levels of specific activity.
Synthesis of daunorubicin‐14‐14C and adriamycin‐14‐14C
Authors: Chen C. Rolland , Fon Mary Tan , Fujiwara Alan N. , Henry David W. , Leaffer Morris A. , Lee William W. , Smith Thomas H.
Published: October 2006

Reaction of adriamycinone with excess14CH3Mgl and periodate cleavage of the resulting glycol (5) affords daunomycinone‐14‐14C (6). Bromination and hydrolysis of 6 gives adriamycinone‐14‐14C (8). Coupling of 6 and the 14‐0‐p‐anisyldiphenyl‐methyl derivative (9) with 1‐chloro‐3‐N‐trifluoroacetyl‐4‐0‐p‐nitrobenzoyldau‐nosamine (10) affords daunorubicin‐14‐14C (1) and adriamycin‐14‐14C (2), respectively, after deprotection.
Tritium labelling of Thaumatin I, a sweet‐tasting protein from Thaumatococcus daniellii benth, by reductive methylation
Authors: van Der Wel H. , Wiersma A. , Brouwer J. N.
Published: October 2006

Thaumatin I has been labelled by reductive methylation of four of the ε‐amino groups of the lysine residues in the protein with tritiated sodium borohydride. Methylation with unlabelled sodium borohydride showed that up to seven amino groups can be methylated without loss of sweet‐ness intensity.

The yield of the tritium‐labelled methylated Thaumatin I was 31% with a tritium incorporation of 4.7%. Its specific radioactivity was 12.8 Ci/mmol.
Synthesis of diethyl 1‐[(13C)methyl]‐3‐phenyl(1,3‐13C2)bicyclo[1.1.0]‐butane‐exo,exo‐2,4‐dicarboxylate
Authors: Pomerantz Martin , Fink Rina
Published: October 2006

The synthesis of the triply13C labeled molecule, diethyl 1‐[(13C)methyl]‐3‐Phenyl(1,3‐13C2)bicyclo[1.1.0]butane‐exo,exo‐2,4‐dicarboxylate is described. The unique feature of the synthesis is that in three instances we employed13CO2(from Ba13CO3) without using a high vacuum line. We found that excellent yields were obtained in two Grignard reagent carbonations and in a CO2reduction using a mechanical pump which produced a vacuum of 0.05 torr. The synthetic sequence involved carbonation of phenylmagnesium bromide to give (α‐13C)benzoic acid, reduction with LiAlH4, conversion to the corresponding benzyl chloride followed by preparation of the Grignard reagent and carbonation to produce phenyl (1,2,‐13C2)acetic acid. Reaction with13CH3Li provided 1‐Phenyl‐2‐(1,2,3‐13C3)‐propanone which, after conversion to its hydrazone and reaction with mercurous trifluoroacetate, yielded 1‐phenyl‐1‐(1,2,3‐13C3)propyne. Reaction twice with carboethoxycarbene (from ethyl diazoacetate) gave the desired triply13C labeled bicyclobutane.
Synthese De La Para‐aminoclonidine Tritiee : Un puissant alpha adrenomimetique
Authors: Rouot B. , Ehrhardt J. D. , Leclerc G. , Schwartz J.
Published: October 2006

The preparation of a tritium labelled alpha‐adrenergic agonist, 2‐(4‐amino‐2,6‐dichloro 3,5‐ditritio‐phenylimino)‐imidazolidine, suitable for alpha‐adrenergic receptor membrane binding studies, is described.
The synthesis of 123m Te‐labeled 17β ‐hydroxy‐2‐tellura‐A‐nor‐5α‐androstane
Authors: Knapp F. F.
Published: October 2006

A microscale synthesis has been developed for the preparation of 17β‐hydroxy‐2‐tellura‐A‐nor‐5α‐androstane. Reactorproduced 123mTe has been used to prepare the 123mTe labeled steroid. The radiochemical synthesis and purification of this potential prostate imaging agent are described in detail.
Mit γ‐Emittern Markierte Steroide ‐ Ester des östradiols und cholestenols mit [103 Ru]‐ruthenocencarbon‐säure
Authors: Hoffmann K. , Rießelmann B. , Wenzel M.
Published: October 2006

Radioactive esters of estradiol and cholestenol with ruthenocene‐carboxylic acid were prepared. In case of the estradiol esters there had been exchange of Fe in the corresponding ferrocene compounds with 103RuCl3 resulting in poor yield only. Good radiochemical yields were obtained by exchanging 103Ru for Fe in (2‐chlorobenzoyl)ferrocene and synthesis of the esters by reaction of estradiol with [103Ru] ruthenocenecarboxylic acid chloride generated from (2‐chlorobenzoyl)ruthenocene. High specific activities of estradiol esters for biochemical studies were achieved after separation of the ferrocene and ruthenocene esters by HPLC.
A study on the electrophilic iodination of chloroquine
Authors: Bakker C. N. M. , Kaspersen F. M. , van Langevelde A. , Oosterhuis J. A. , Pauwels E. K. J.
Published: October 2006

Chloroquine can be iodinated with radioactive iodine in radiochemical yields 60‐75% with chloramine‐T or H2O2/lactoperoxidase. With both methods a rather complex mixture of labelled products is formed. The yield and ratios of the labelled products depend upon the chloroquine‐concentration, the amount of carrier iodide present and in the case of the chloramine‐T method, the chloramine‐T concentration. With the chloramine‐T method the main product is 3‐iodochloroquine, with H2O2/lactoperoxidase an unidentified iodinated chloroquine‐derivative, probably a dimer, is the main labelled product. With chloramine‐T products such as 3‐chlorochloroquine and deethylchloroquine are formed in mass amounts.
Synthesis and characterization of 5‐methyl‐1‐phenyl‐3,4,5,6‐tetrahydro‐1H‐2,5‐benzoxazocine‐1,3,4,6‐13C hydrochloride (Nefopam‐13C hydrochloride)
Authors: Bunker James E. , Newmark Richard A.
Published: October 2006

Nefopam hydrochloride (I), an analgesic agent, was labelled with carbon‐13 at C‐1,3,4 and 6 positions for metabolic studies. The starting materials for the synthesis included commercially available phthalic acid‐carboxyl‐13C1 (II) and 2‐methylaminoethyl‐1,2‐13C2 alcohol. The extent of isotope enrichment was determined by nuclear magnetic resonance and mass spectroscopy. The overall yield of I was 34% from phthalic acid‐carboxyl‐13C.
Synthesis of 3‐indolyl(1‐14C)acetic, 3‐indolyl(2‐14C) acetic and 3‐indolyl(1,2‐14C2)acetic acids
Authors: Viswanathan K. V. , Ramaamurthy T. V.
Published: October 2006

The synthesis of 3‐indolylacetic acid labelled with 14C in side chain carbon atoms has been effected using (1‐14C)glycolic acid, (1,2‐14C2)glycolic acid and (2‐14C)glycolic acid in an yield of 40‐60%. Some of the parameters that affect the synthesis have been studied and the results are reported in this paper.
Synthesis of trans‐[13,14‐14C2]‐retinoic acid
Authors: Kaegi Heinz , Chew Edward , Chien Ping‐Lu
Published: October 2006

Trans‐[13,14‐14C2]‐Retinoic acid has been synthesized by condensation of β‐ionylideneacetaldehyde and 14C‐labeled methyl senecioate in the presence of potassium amide in ether. A convenient synthesis of the key intermediate, methyl (diethoxyphosphinyl)‐[2‐14C]acetate, is also described.
The synthesis of pyrrole derivatives labelled with 13C in selected positions: Improved procedures
Authors: D'alessandro Giuliana. , Sleiter Giancarlo
Published: October 2006

Starting from sodium acetate‐1‐13C or ‐2‐13C improved procedures for the preparation of ethyl acetoacetate‐2,4‐13C2, ethyl acetoacetate‐1,3‐13C2, ethyl acetoacetate‐2‐13C, and ethyl acetoacetate‐2,3‐13C2 are described. A method was also worked out which allows, using the labelled ethyl acetoacetates, to obtain Knorr's pyrrole (diethyl 3,5‐dimethyl pyrrole‐2,4‐dicarboxylate) carrying the label in well‐defined positions in excellent yields. An example is given of further transformation of Knorr's pyrrole.
Synthesis of indium‐111 mesoprotoporphyrin IX
Authors: Lee K. M. , Marshall A. G.
Published: October 2006

Indium‐111 mesoprotoporphyrin IX has been prepared by refluxing suitable proportions of InCl3, sodium acetate, and mesoprotoporphyrin IX in glacial acetic acid. The labeled metalloporphyrin is sufficiently water‐soluble for use as a scanning agent, and can also be incorporated into heme apoproteins for perturbed gamma‐gamma angular correlation measurements.
14C‐labelling of optically active fenvalerate, α‐cyano‐3‐phenoxy‐benzyl (S)‐2‐(4‐chlorophenyl)‐3‐methylbutyrate (I)
Authors: Yoshitake Akira , Kanamaru Hiroshi , Shono Fumiaki , Nakatsuka Iwao
Published: October 2006

(S)‐Fenvalerate (α‐cyano‐3‐phenoxybenzyl) (S)‐2‐(4‐chlorophenyl)‐3‐methylbutyrate, a novel insecticide, was labelled with carbon‐14 individually at the carbonyl (1a), the cyano (1b) and the alcoholic methyne (1c) carbons for use in metabolic studies. Isopropylation of 4‐chlorophenylacetonitrile‐14C with isopropyl bromide followed by hydrolysis gave racemic 2‐(4‐chlorophenyl)‐3‐methylbutyric‐1‐14C acid, which on optical resolution with (−)‐1‐phenylethylamine gave the (S)‐acid. Esterification of the (S)‐acid with α‐cyano‐3‐phenoxybenzyl bromide gave 1a in 18% yield from potassium cyanide‐14C. Esterification of α‐cyano‐14C‐3‐phenoxybenzyl alcohol with (S)‐2‐4‐chlorophenyl‐3‐methyl‐butanoyl chloride (9) gave 1b in 65% yield. Condensation of 3‐phenoxybenzaldehyde‐(carbonyl‐14C), prepared from 3‐phenoxybenzoic‐14 C acid, with 9 and sodium cyanide gave 1c in 54% yield from barium carbonate‐14C.
Synthesis of [1‐14C]n‐heptane
Authors: David G. G. , Morris D. F. C. , Short E. L.
Published: October 2006

Synthesis of n‐heptane labelled with carbon‐14 in the 1‐position is described. The precedure involves five steps starting with reaction of [14C]carbon dioxide with n‐hexyl magnesium bromide and finishing with reduction of [1‐14C]n‐heptyl bromide. The purity of the final product was more than 97% and the overall yield was 36%.
The synthesis of aliphatic and aromatic hydrocarbons containing methyl groups labelled with 11C
Authors: Långstro̊m B. , Sjöberg S.
Published: October 2006

The synthesis of [1‐11C]pentane, [1‐11C]nonane, [1‐11C]‐ undecane, 2‐[11 C]methyl‐naphthalene and [11C]methyl‐benzene (toluene) are reported. The hydrocarbons were prepared by the coupling reaction between [11C]methyl iodide and the appropriate lithium organocuprate. Toluene was also labelled by the coupling reaction between phenyllithium and [11C]methyl iodide. The reactions were carried out in ether giving the 11C‐labelled hydrocarbons in radiochemical yields < 90% with short reaction times (3‐13 min). The overall synthetic time from [11C]carbon dioxide was 9–19 min.
Synthese biologique des acides ferulique et sinapique marques AU 14C
Authors: Marigo G. , Boudet D. Riviere
Published: October 2006

14CH3 labelled ferulic and sinapic acids have been synthesized through an enzymic methylation of caffeic and 5‐hydroxyferulic acids using labelled S‐adenosyl methionine as 14CH3 donor. The methyltransferases involved which were extracted from stems of Poplar catalyse these reactions with a good efficiency. A purification procedure of 14C S‐adenosyl methionine is described which allows the recycling of 14CH3 donor. The yield of the overall process is therefore greatly improved. This method allows the synthesis of products with high specific radioactivity.

Les acides férulique et sinapique marqués au 14C sur le groupement méthyle ont été synthétisés par voie enzymatique à partir des acides caféique et 5‐hydroxyférulique en utilisant la S‐adénosyl méthionine radioactive comme donneur de 14CH3. Le biocatalyseur utilisé, la O‐méthyltransférase, est issu de tiges de Peuplier. Dans les conditions optimales de la réaction, cette enzyme est capable d'assurer la formation des deux acides phénoliques avec un rendement intéressant. La mise au point d'un protocole de purification du donneur de 14CH3 permettant sa réutilisation, améliore la rentabilité de ce mode de synthèse dont l'intérět consiste en l'obtention de produits d'activité spécifique élevée.
Yellow mustrad oil as a latent quinone methide: A conventient preparation of p‐hydroxybenzyl [14C]cyanide
Authors: Jaroszewski Jerzy W. , Szancer Joseph , Ettlinger Martin G.
Published: October 2006

Naturally derived p‐hydroxybenzyl isothiocyanate, a hitherto unconsidered example of the rare class of stable p‐hydroxybenzylating agents, was used for preparation of labelled p‐hydroxybenzyl cyanide.
Synthesis of 77Br‐labelled 2‐(4‐bromo‐2,5‐dimethoxyphenyl)‐isopropylamine with high specific activity
Authors: Coenen H. H.
Published: October 2006

The tagging of 2,5‐dimethoxyphenylisopropylamine (DPIA) with bromine‐77 (T1/2 = 56 hrs) was reinvestigated in order to achieve high specific activities which are necessary for in‐vivo application of this centrally acting drug. A fast one‐pot synthesis was developed using N‐chlorotetrafluorosuccinimide (NCTFS) and practically carrier‐free bromide to introduce radiobromide into the aromatic ring. Trifluoroacetic anhydride (TFA) was applied both as solvent and as a reversible blocking agent of the free amino group. TFA was also shown to suppress chlorinating sidereactions. Rapid separation of 4‐77Br‐2,5‐dimethoxyphenylisopropylamine was achieved by reverse phase high pressure liquid chromatography. The total labelling and separation procedure takes about two hours, and 4‐77Br‐DOB is obtained with an overall radiochemical yield of 25% and a specific activity of <8 Ci/μmole.
Synthesis of 6,7‐dihydro‐10‐trideuteromethyl‐6, 8, 8‐trimethyl‐8H‐pyrano[3,2‐g]chromone‐2‐carboxylic acid
Authors: Minami Norio
Published: October 2006

Synthesis of 6,7‐dihydro‐10‐trideuteromethyl‐6,8,8‐trimethyl‐8H‐pyrano[3,2‐g] chromone‐2‐carboxylic acid (10) in high isotopic purity is described. The trideuteromethylation was achieved by sodium borodeuteride reduction of the ethoxycarbonyl derivative (5) of 7‐hydroxy‐2,2,4‐trimethylchroman‐8‐carboxylic acid (4). This labelled compound (10) is required for use as mass spectrometric stable isotope internal standard for the study of metabolic fate of 6,7‐dihydro‐6,8,8,10‐tetramethyl‐8H‐pyrano[3,2‐g] chromone‐2‐carboxylic acid (9), which is an orally active antiallergic agent.
Biosynthetic methods for incorporating positron‐emitting radionuclides into compounds of biomedical interest
Authors: Gelbard Alan S.
Published: October 2006

The progress that has been made in incorporating the short‐lived, positron‐emitting isotopes N‐13 and C‐11, into biologically active compounds by biosynthetic means is reviewed. These methods include the use of whole cells or plant leaves to carry out a sequence of metabolic reactions, such as nitrogen fixation or photosynthesis, and the use of purified enzymes to catalyze specific chemical reactions, to form the labeled compounds.
Synthesis of (2S, 5R) ‐ [5‐2H] Proline
Authors: Gramatica Paola , Manitto Paolo , Manzocchi Ada , Santaniello Enzo
Published: October 2006

The title compound was obtained by preferential crystallisation of (2RS,5R)‐[5‐2H]proline. The labelled racemic amino acid was synthesized in five steps from (5R)‐[5‐2H]‐2‐pyrrolidone, which was prepared by cyclisation of (4R)‐[4‐2H] GABA. The stereospecific label was introduced into GABA enzymatically decarboxylating in 2H2O (2S)‐glutamic acid, in the presence of glutamate decarboxy lase from E. coli.
Synthese de la pentamethylmelamine (noyau 14C‐4,6), un nouvel agent antitumoral
Authors: Do‐cao‐thang  , Nguyen‐hoang‐nam  , Hoellinger H. , Pichat L.
Published: October 2006

(ring‐4,6‐14C) Pentamethylmelamine (14C‐PMM), a new antitumor agent, was prepared from barium (14C) carbonate by a 6 step synthesis. (14CN) Dimethylcyanamide, prepared from sodium (14C) cyanide with 71% yield and treated with phosgene in the presence of hydrogen chloride, was cyclized to (ring‐4,6‐14C)‐2‐chloro‐4,6‐bis (dimethylamino)‐s‐triazine. The latter was purified by silicagel low pressure liquid chromatography (15% yield based on nitrile) and condensed with monomethylamine to give 14C‐PMM. After purification 14C‐PMM was obtained with 91% yield, specific activity = 38 mCi/mMole. The mechanism of the reaction of nitrile with phosgene was discussed.
A simple synthesis of L‐[35S]cysteine sulfinic acid
Authors: Spears Ronald M. , Martin David L.
Published: October 2006

The synthesis of L‐[35S]cysteine sulfinic acid (L‐2‐amino‐3‐[35S] sulfino‐propanoic acid) in 65% yield from S‐[35S]cystine is described. The procedure was designed for use with milligram quantities of starting material and requires no purification of intermediates. L‐[35S]Cystine was converted first to its thiosulfonate. Subsequent reaction of the thiosulfonate with ammonium hydroxide generated L‐[35S]cysteine sulfinic acid and L‐[35S]cystine as the major products. The L‐[35S]cystine was recovered and reprocessed thereby increasing the yield.
Synthesis of 14C‐labeled N‐nitrosobis (2‐oxopropyl) amine
Authors: Nagel D. , Kupper R.
Published: October 2006

N‐Nitrosobis (2‐oxopropyl) amine (BOP), a potent and selective pancreatic carcinogen in the Syrian golden hamster was synthesized with a 14C label in the alpha carbon. Oxidation of 2‐hydroxypropyl‐2‐hydroxypropyl‐1‐14C‐amine followed by nitrosation with sodium nitrite and hydrochloric acid gave radiolabeled BOP in 60% yield.
Potential drugs labelled with 14C. II. Synthesis of 1‐cyano‐3‐imino‐8, 9‐dimethoxy‐3, 4,5,6‐ ‐tetrahydro‐thiazolo[4, 3‐a]isoquinoline hydrochloride
Authors: Koltai E. , Zólyomi G. , Komáromy P. , Bánfi D. , Szüts T. , Takács K.
Published: October 2006

The synthesis of 1‐cyano‐3‐imino‐8,9‐dimethoxy‐ ‐3,4, 5,6‐tetrahydro‐thiazolo [4,3‐a]isoquinoline hydrochloride labelled with 14C in five different positions: in position 3 (1a), in the cyano group at position 1 (1b), in position 5 (1c), in position 10b (1d) and in the methoxy groups at position 8 and 9 (1e) was carried out.
Synthesis of specifically‐deuterated procaine and tetracaine
Authors: Boulanger Yvan , Leitcht Leonard C.
Published: October 2006

Local anesthetics procaine and tetracaine have been specifically‐deuterated in two and three positions, respectively, for use in deuterium nuclear magnetic resonance experiments. The experimental procedure is either new or an adaptation of early synthetic methods.
Adaptation de methodes classiques a la synthese de glycerophospholipides marques au carbone 14
Authors: Dana J. L. , Pichat L.
Published: October 2006

Classical phospholipids syntheses were selected and adapted to the preparation of natural glycerophospholipids labelled with carbon 14 in the acyl moiety. 1,2‐(14C) diacyl‐3‐bromo sn‐glycerol was the starting material.

Saturated 14C‐phosphatidyl‐ethanolamine, choline and serine were obtained in 30 %, 25 % and 11 % yields relative to the 14C‐fatty acid, by condensation of a suitably protected amino‐alcohol with a (14C‐diacyl) phosphatidic acid in presence of triisopropyl‐benzenesulfonyl‐chloride followed by deprotection of the amino group.

The synthesis of unsaturated (or mixed) 14C phosphatidyl ethanolamine was achieved, with a 28 % yield, by condensation of the 14C‐diacyl‐bromoglycerol with the silver salt of the N‐trityl aminoethyl and benzyl diester of phosphoric acid and subsequent deprotections.
Tritium labelled compounds of high specific activity I. Tofizopam
Authors: Zólyomi G. , Horváth Gy. , Láng T. , Kórösi J.
Published: October 2006

The possibilities of tritium labelling of tofizopam (1) at high specific activity were investigated. Two methods, one by isotopic exchange, and one by catalysed halogen‐tritium replacement were developed. The latter was found to be more rational, and 1 specifically labelled with tritium at a specific activity of 12 Ci/mmole was prepared by applying this route. An attempted labelling by catalysed multiple bond reduction with tritium is also described.
Preparation of selectively side‐chain deuteriated pyridines via pyrylium salts
Authors: Balaban Alexandru T.
Published: October 2006

Isotopic exchange of benzylic hydrogens in α‐ and β‐alkyl side‐chains of pyrylium salts occurs readily by heating in deuterium oxide at normal pressure. As β‐hydrogens exchange faster than α‐hydrogens, one may obtain selective (about 90 % isotopic purity) β‐ or α‐deuteriation of side‐chains by direct or reverse isotope exchange. The deuteriated pyrylium salts are converted by aqueous ammonia into the corresponding pyridines without loss of deuterium. Examples presented are : 2,4,6‐tri‐(d3‐methyl)‐, 2,6‐di‐(d3‐methyl)‐4‐methyl‐, 2,6‐dimethyl‐4‐(d3‐methyl)‐, 2,6,‐di‐(d3‐methyl)‐3,5‐dimethyl‐, 2,4,6‐tri‐(d3‐methyl)‐3,5‐di‐methyl‐, 2,6‐di‐(α‐d2‐ethyl)‐4‐(d3‐methyl)‐, 2,6‐diethyl‐4‐(d3‐methyl)‐, and 2,6‐di‐(α‐d2‐ethyl)‐4‐methyl‐pyrylium perchlorates and ‐pyridines.
The use of the acetonide derivative in the preparation of D‐threo‐chloramphenicol‐1‐3H and its nitroso derivative
Authors: Heys J. Richard
Published: October 2006

An efficient synthesis of millimolar quantities of high specific activity D‐threo‐chloramphenicol‐1‐3H is described. The key step is the chromatographic separation of the compound from its 1‐epimer, produced in the Ca(B3H4)2 reduction of chloramphenicol ketone (D‐α‐dichloroacetyl‐amino‐β‐hydroxy‐p‐nitropropiophenone), by use of the acetonide derivative. Stereochemical aspects of the N‐bromosuccinimide oxidation of chloramphenicol to chloramphenicol ketone have been investigated, and the previously reported [1] specific rotation of chloramphenicol ketone has been corrected. The synthesis of nitrosochloramphenicol‐1‐3H is described.
Synthesis of 14C‐labeled 4‐acetyl‐5,6‐bis(4‐chlorophenyl)‐2‐(2‐hydroxyethyl)‐2H‐pyridazin‐3‐one
Authors: Buchman Russell , Evans T. R.
Published: October 2006

A simple and convenient synthesis of a radiolabeled antihypertensive pyridazinone was developed. The product was purified chromatographically, and the chemical and radiochemical purities of the sample were determined.
Synthesis of carbon‐14‐labelled antibacterial agent. Synthesis of 1‐ethyl‐ [1‐14C]‐6‐fluoro‐1, 4‐dihydro‐4‐oxo‐7‐ (1‐piperazinyl)‐3‐quinolinecarboxylic acid (14C‐AM‐715)
Authors: Nagatsu Y. , Irikura T.
Published: October 2006

1‐Ethyl‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐7‐(1‐piperazinyl)‐ 3‐quinolinecarboxylic acid (I, AM‐715), a new potent antibacterial agent, was labelled with carbon‐14 at the C‐1 position of the N‐ethyl group for metabolic studies. The synthesis was achieved according to two reaction routes. The overall radiochemical yields of 14C‐AM‐715 based on ethyl iodide‐1‐14C from route A and route B, were 29.4% and 9.4%, respectively.
Synthesis of methionines specifically labelled with 2H or 13C
Authors: Billington David C. , Golding Bernard T. , Kebbell Michael J. , Nassereddin Ishaq K.
Published: October 2006

Efficient methods for synthesising L‐[methy‐ 13C]methionine from [13C]iodomethane and L‐methionine, and L‐[3,4‐13C2] methionine from [13C2]ethene, are described; the preparation of [3,3‐2H2]methionine and [2,3,3‐2H3]methionine from methionine by an exchange method is detailed.
A simple, one‐step synthesis of 1‐14C‐acetylhydrazine
Authors: Mathiaparanam P. , Wong L. T. , Thomas B. H.
Published: October 2006

A synthesis of 1‐14C‐acetylhydrazine by acetylation of hydrazine using 1‐ 14C‐ethyl acetate and a catalytic amount of activated alumina is described.
A novel synthesis of ethanolamine‐2‐14C
Authors: Koltai E. , Horváth B. , Bánfi D.
Published: October 2006

Ethanolamine‐2‐14C was prepared by the reduction of benzyloxycarbonyl‐glycine‐1‐14C methyl ester. The reduction was carried out with calcium borohydride and the protecting group was removed by hydrogenolysis.
Decay synthesis of carrier‐free 3‐methyl‐ [3H] ‐furan and 2‐methyl‐[3H] ‐furan
Authors: Speranza Maurizio , Angelini Giancarlo , Sparapani Cinzia
Published: October 2006

Nuclear decay of C3H4 in the presence of gaseous furan represents a simple and convenient synthetic route to carrier‐free multitritiated 3‐methyl‐ and 2‐methyl‐furan. Their application for biological studies appears particularly promising, on account of the favourable characteristics of the followed synthetic approach.
Rapid catalytic synthesis of 11C‐labelled aromatics
Authors: Speranza Maurizio , Ferrieri Richard A. , Wolf Alfred P. , Cacace Fulvio
Published: October 2006

11C‐Labelled benzene derivatives were prepared catalytically by trimerizing acetylene‐11C with acetylene and propyne carriers over 1.5 grams of silica‐alumina support activated by potassium chromate (0.2% by weight). Optimized yields of the 11C‐labelled aromatics were obtained when the reactants were exposed to the catalyst for 10 minutes at 24°C. A minimum addition of 50 μmole of alkyne carrier was necessary before the trimerization proceeded to give appreciable yields of 11C‐labelled aromatics. In the competitive trimerization of acetylene‐11C with acetylene and propyne carriers, three 11C‐labelled aromatic products were generated: benzene, toluene, and xylene. From these studies acetylene was observed to be 1.6 times more reactive than propyne. In addition, the observed distribution of 11C‐labelled xylenes (3.4% ortho, 10.6% meta, and 86% para) indicates an apparent regiospecificity in the trimerization of 11C‐acetylene with propyne.
Synthesis of [2‐13C, 2‐14C]2‐aminoethanol, [1‐13C, 1‐14C]2‐chloroethylamine, N,N′‐bis([1‐13C, 1‐14C]2‐chloroethyl)‐N‐nitrosourea(BCNU) and N‐([1‐13C, 1‐14C]2‐chloroethyl)‐N‐nitrosourea(CNU)
Authors: Narayan Ramani , Chang Ching‐Jer
Published: October 2006

[2‐13C, 2‐14C]2‐Aminoethanol hydrochloride was prepared in good yield from Na*CN in a two step sequence by first converting the Na*CN to OHCH2*CN and then reducing the nitrile directly with a solution of borane‐tetrahydrofuran complex. The reaction procedure was simple and the pure product could be obtained readily. Using this specifically labelled precursor, the synthesis of [1‐13C, 1‐14C]2‐chloroethylamine hydrochloride, N‐([1‐13C, 1‐14C]2‐chloroethyl)‐N‐nitrosourea(CNU) and N,N′‐bis([1‐13C, 1‐14C]2‐chloroethyl)‐N‐nitrosourea(BCNU) in good yield without isotope scrambling was also reported.
Tritium labelling of psychopharmacologic agents
Authors: Buchman Ouri , Shimoni Michael
Published: October 2006

Attempts to reach phenothiazine derivatives labelled with tritium at high specific activity, are described. All the syntheses are based on catalysed dehalogenation procedures. The most encouraging results are those obtained by halogenation of the desired compound followed by catalytic dehalogenation with Pd/C. The specific activities are in the range of 10,000‐40,000 mCi/mmol.
Synthese du dimethindene (indenyl‐14C‐1)
Authors: Mestre P. , Noel J. P. , Pichat L. , Benakis A.
Published: October 2006

Synthesis of (1‐14C‐indenyl) dimethindene (7‐14C) benzyl chloride prepared from (14C) barium carbonate is condensed with diethyl sodio malonate to give diethyl (7‐14C) benzyl malonate : 4 in a yield of 78 %. 4 is then alkylated with 2‐dimethylamino 1‐chloroethane to give the diethyl dialkylmalonate : 12. 12 is saponified with sodium hydroxide, decarboxylited by treatment with hot hydrochloric acid and cyclised with polyposphoric acid into 2‐(2‐dimethyl aminoethyl) 3‐(1‐ C) indanone : 8. This indanone is condensed with 2‐(2‐lithioethyl) pyridine, the intermediate is dehydrated into (1‐ C indenyl) Dimethindene which is isolated and purified as its maleate salt. Specific activity is 54 mCi/mMole. Radiochemical purity checked by TLC is better than 99%. The overall yield is 15.8 % based on barium carbonate.
The preparation of carbon‐14 and tritium labelled 1‐[4‐(2‐dimethylaminoethoxy)phenyl]‐1, 2‐diphenyl‐1‐butene [ICI 46,474, tamoxifen (‘nolvadex’)] and the separation of cis‐trans isomers I. The synthesis of carbon‐14 labelled tamoxifen (‘nolvadex’)
Authors: Burns J , Rutter D
Published: October 2006

The preparation of [14C]tamoxifen from [U‐14C]bromobenzene is described. Several preparations of the compound have been made with overall radiochemical yields of 12% ‐ 14%, and specific activities 1.3 to 10.1 mCi/mmol have been obtained.

The purification procedures used, including the separation of the cis‐trans isomers by preparative thin layer chromatoqraphy, are also described.
Synthesis of triamcinolone acetonide‐4‐14C
Authors: Rao Pemmaraju Narasimha , Cessac James W. , Hill Kenneth A.
Published: October 2006

The free hydroxyl groups in triamcinolone acetonide (1) were protected as silyl ethers to give the bis‐silyloxy derivative 4. Compound 4 was then hydrogenated over 5% palladium on carbon to give the Δ4‐3‐oxo steroid 5 which was then converted to the enol‐lactone 7 under selective reaction conditions. The enol‐lactone 7 was subjected to Grignard reaction with 14C‐methylmagnesium iodide to give an adduct 8a which on subsequent treatment with lithium 2,6‐di‐t‐butylphenoxide gave 4‐14C‐Δ4‐3‐oxo derivative 9. Compound 9. was heated with selenium dioxide in t‐butanol containing pyridine to give the Δ1,4‐3‐oxo derivative 10. Removal of the silyl protecting groups was readily accomplished by heating 10 with hydrochloric acid in methanol‐tetrahydrofuran solution to give the title compound 11.
Syntheses of some di‐, tetra‐, and hexadeuterio‐octadecenoates
Authors: Dejarlais W. J. , Emken E. A. , Miller W. R.
Published: October 2006

(E&Z)‐10‐Octadecenoic‐13,14‐d2, −14,15‐d2, and −14,14,15,15‐d4 acids were prepared by Wittig synthesis. (E&Z)‐11‐Octadecenoic‐14,14,15,15,17,18‐d6 acids were prepared by Wittig synthesis and by synthesis and reduction of 11‐octadecynoic‐14,14,15,15,17,18‐d6 acid. Overall yield in 11‐octadecenoate‐d6 synthesis was better by the Wittig procedure (25% vs. 15%). The Wittig‐produced 11‐octadecenoates had higher hexadeuterio contents than the acetylenic sequence products (85% vs. 70%) but the average isotopic purity was similar (5.9 D/mole). The Wittig method appears better for deuterium‐labelled octadecenoate synthesis.
Synthesis of dexamethasone‐4‐14C
Authors: Rao Pemmaraju Narasimha , Cessac James W. , Hill Kenneth A.
Published: October 2006

The bismethylenedioxy (BMD) derivative of dexamethasone 2 was silylated with trimethylchlorosilane and imidazole in dimethylformamide to give the 11β‐trimethylsilyloxy BMD derivative 3. The Δ1 ‐double bond in 3 was hydrogenated over 5% palladium on carbon to give the Δ4‐3‐oxo steroid 4. Oxidation of 4 with potassium permanganate‐sodium metaperiodate gave the seco‐acid 5 which on subsequent treatment with acetic anhydride; sodium acetate and triethylamine gave the enol‐lactone 6. The enol‐lactone 6 was reacted with 14C‐methylmagnesium iodide to give an adduct 7a which on heating at reflux with lithium 2,6‐di‐t‐butylphenoxide in dioxane gave the Δ4‐3‐oxo derivative 8. Compound 8 was heated at reflux with m‐iodylbenzoic acid and diphenyl diselenide in toluene to give the Δ1,4‐3‐oxo steroid 9. The protecting BMD and silyl groups were removed in a single step by reaction with aqueous trifluoroacetic acid containing 2N hydrochloric acid at room temperature to give dexamethasone‐4‐14C 10.
Synthesis of [4a‐13C]‐6‐methyltetrahydropterin
Authors: Lazarus Robert A. , Sulewski Michael A. , Benkovic Stephen J.
Published: October 2006

The synthesis of [4a‐13C]‐6‐methyltetrahydropterin, a synthetic cofactor for phenylalanine hydroxylase, is described. [2‐13C]‐ethyl bromoacetate was converted in four steps to [5‐13C]‐2,4‐diamino‐6‐hydroxypyrimidine in 86% yield. The latter was nitrosated, reduced, condensed with pyruvic aldehyde, and reduced to afford pure [4a‐13C]‐6‐methyltetrahydropterin in a net overall yield of 16%.
Synthesis and evaluation of 82Br and 77Br labeled (17α, 20E)‐21‐bromo‐19‐norpregna‐1,3,5(10),20‐tetraene‐3,17β ‐diol
Authors: Hanson Robert N. , El‐Wakil Hoda , Murphy Francis , Scott Wilbur D.
Published: October 2006

17α ‐E‐Bromovinylestradiol and its radiobrominated analogs were prepared by halodestannylation. The synthesis was achieved by bromination of the tri‐n‐butylstannylvinyl intermediate to give a 90% isolated yield. The reaction of the intermediate with ammonium [82Br] bromide or sodium [17Br] bromide in the presence of an oxidant give the corresponding radiolabeled bromovinylestradiol in 80–90% yields after isolation by HPLC. The radiochemical purity was greater than 98% and no other UV‐active compounds could be detected by HPLC. An in vivo comparison of this compound with the previously prepared 17α ‐E‐[125I]iodovinyl estradiol indicated that the two compounds had similar uterine uptake and specific receptor binding properties. The results suggest that radiobromodestannylation may be the method of choice for the preparation of this and other structurally similar compounds.
Synthesis of [14C] labelled N‐nitro methylamine and N‐nitro dimethylamine
Authors: Braun H. , Plesch W. , Frei E. , Hassel M. , Wiessler M.
Published: October 2006

N‐nitro [14C]methylamine was synthesized by the alkaline cleavage of N‐nitro[methyl‐14C] methylurethane obtained by nitration of [N ‐ methyl‐14C] methylurethane. N‐nitro[N‐methyl‐14C]dimethylamine could be obtained by methylation of monomethylnitramine with [14C] diazomethane.
Synthesis of 13C warfarin labelled at the hemiketal carbon, and its resolution
Authors: Savell Van Henry , Valente Edward J. , Eggleston D. S.
Published: October 2006

Warfarin (cyclic hemiketal form: 2‐hydroxy‐2‐methyl‐4‐phenyl‐3,4‐dihydro‐2H,5H‐pyrano[3,2‐c][1]benzopyran‐5‐one) is labeled with 98+% 13C at the anomeric carbon (C2) and resolved into its enantiomers. Acetone‐2‐13C(98.6%) condenses with benzaldehyde in aqueous base to produce 4‐phenyl‐3‐buten‐2‐one‐2‐13C(98+%). Michael‐type addition of this to 4‐hydroxycoumarin in methanol produces the labeled diastereomeric warfarin methyl ketals which on deprotection form racemic warfarin‐2‐13C(98+%). Classical resolution of labeled warfarin with quinidine produces partly resolved (S)‐(–)‐warfarin‐2‐13C(98+%). Labeled warfarin is a suitable probe for warfarin configuration for which three distinct isomeric forms are known.
Synthesis of Some 3H labeled 2′, 3′‐dideoxynucleosides of pharmacological interest
Authors: Taylor George F. , Kepler John A.
Published: October 2006

[Pyrimidine‐5‐3H]2′, 3′‐dideoxycytidine and [ribose 2,3‐3H]2′, 3′‐dideoxyinosine are prepared by catalytic reduction with tritium gas. [Adenine‐8‐3H]2′3′‐dideoxyadenosine is prepared by catalytic exchange with tritium gas. [Hypoxanthine‐8‐3H]2′,3′‐dideoxyinosine is prepared by the action of adenosine deaminase on [adenine‐8‐3H]2′,3′‐dideoxy‐adenosine.
Peracetic acid as a superior oxidant for preparation of [123I]IBZM: A potential dopamine D‐2 receptor imaging agent
Authors: Kung Mei‐Ping , Kung Hank F.
Published: October 2006

Various oxidizing agents: chloramine‐T, hydrogen peroxide, sodium persulfate, m‐chloroperoxybenzoic acid and peracetic acid were examined as the oxidant for preparing radioiodinated IBZM ((S)‐(–)‐3‐ iodo‐2‐hydroxy‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide), which is a useful dopamine D‐2 receptor imaging agent. Of all the oxidizing agents tested, peracetic acid appears to be the best agent for no‐carrier added radioiodination. The advantages of using peracetic acid as the oxidant for the preparation of [125I] or [123I] IBZM include: high radiochemical yield, high radiochemical purity, and short reaction time at room temperature.
A general synthetic method suitable for the introduction of deuterium or tritium in buspirone type anxiolytic agents
Authors: Welch Willard M. , Viverios D. M.
Published: October 2006

In recent years, a number of putative non‐benzodiazepine anxiolytic agents incorporating the 4‐ aminobutylimide or sulfonamide‐imide linkage have been reported and at least two of these, buspirone and gepirone, have been shown to have anxiolytic activity in man. In order to study the metabolism, body distribution and binding affinities of this class of compound, it was of interest to devise a precursor which could be specifically labelled with tritium to high specific activity. We have devised a synthetic route to the corresponding but‐2‐ynyl and but‐2‐enyl analogs of gepirone and have converted the latter to dideuterogepirone as an example of the methodology. Thus the method chosen has been found to be practical and is believed to be of sufficient generality to enable the synthesis of a variety of derivatives of this type containing either two or four atoms of label. Furthermore by appropriate choice of reagents, incorporation of 14C into these compounds may be achieved.
Synthesis and evaluation of biological activity of two novel tritium‐labeled derivatives of riodipine
Authors: Shevchenko V. P. , Myasoedov N. F. , Soldatov N. M. , Duburs G. J. , Kastron V. V. , Skrastinš I. P.
Published: October 2006

2, 6‐Dimethyl‐3‐methoxycarbonyl‐5–([2, 3‐3H2] ‐n‐propoxy‐carbonyl)‐4‐(2′ ‐difluoromethoxyphenyl)‐1, 4‐dihydropyridine and 2, 6‐dimethyl‐3, 5‐di([2, 3‐3H2] ‐n‐propoxycarbonyl)‐4‐(2′‐difluoromethoxyphenyl)‐1, 4‐dihydropyridine were prepared by catalytic tritiation of the respective 3‐allyloxy‐carbonyl and 3,5‐di (allyloxycarbonyl) derivatives of riodipine. The two novel radioactively labeled 1,4‐dihydropy‐ridine derivatives obtained were shown to be suitable molecular tools for the identification of membrane‐bound and solubilized dihydropyridine receptors associated with calcium channels in rabbit skeletal muscle.
Synthesis of carbon‐14 and tritium labeled dopamine beta‐hydroxylase inhibitors of the imidazolinethione type
Authors: Senderoff S. G. , Shilcrat S. C. , Levinson S. H. , Heys J. R.
Published: October 2006

1‐[(3,5‐Difluoro‐4‐hydroxyphenyl)methyl]‐1,3‐dihydro‐2H‐imidazole‐2‐thione, 1‐[(3,5‐difluoro‐4‐methoxyphenyl)methyl]‐1,3‐dihydro‐2H‐imidazole‐2‐thione, and 1‐[(3,5‐difluorophenyl)methyl]‐1,3‐dihydro‐2H‐imidazole‐2‐thione (SK&F 102048, SK&F 102055 and SK&F 102698, respectively) were synthesized in carbon‐14 and tritium labeled forms. Carbon‐14 from potassium [14 C]thiocyanate was incorporated into the imidazolethione ring of SK&F 102055 and SK&F 102698 at C‐2 by condensation with N‐(2,2‐dimethoxyethyl)‐3,5‐difluoro‐4‐methoxybenzenemethanamine or N‐(2,2‐dimeth‐oxyethyl)‐3,5‐difluorobenzenemethanamine. Treatment of SK&F [2‐14 C] 102055 with boron tribromide gave SK&F [2‐14 C] 102048. Tritiated SK&F 102048 was synthesized by sodium [3H]borohydride reduction of N‐(3,5‐difluoro‐4‐methoxyphenylmethylene)‐2,2‐dimethoxy‐ethanamine, followed by condensation with potassium thiocyanate and demethylation with boron tribromide.
Structure biodistribution relationship of radiolabeled ergolines: Search for brain imaging radiopharmaceuticals
Authors: Basmadjian G. P. , Sadek S. A. , Mikhail E. A. , Parikh A. , Weaver A. , Mills S. L.
Published: October 2006

A series of ergoline derivatives, analogues of Pergolide 1 and Lysergol 6, were synthesized, radiolabeled with 125I or 75Se, and evaluated for their ability to cross the Blood Brain Barrier of rats, for potential use as radiopharmaceuticals for imaging the brain. Introduction of the radiolabel was either at the 17‐ position (attached to the 8β‐methylene) or at the 2‐ position of the indole portion of the ergoline moiety. Of the 8 radiolabeled compounds tested, two pergolide analogues, 8β‐(methyl‐75Seseleno)‐methyl‐6‐propyl ergoline 5 and 8β−[125I]‐iodomethyl‐6‐propyl ergoline 2f showed the highest uptake in the brain, adrenal and heart with good organ to blood ratios. This work has shown that analogues of pergolide, a dopamine agonist, if labeled with 123I may yield a clinically useful brain imaging radiopharmaceutical.
Synthesis of 7‐benzyl‐7‐aza‐3‐thiabicyclo[3.3.1]nonane hydroperchlorate‐6,8,10‐14C3
Authors: Zisman Stan A. , Darrell Berlin K. , Alavi Fereidon K. , Sangiah Subbiah , Clarke Cyril R. , Scherlag Benjamin J.
Published: October 2006

A synthesis of 7‐benzyl‐7‐aza‐3‐thiabicyclo[3.3.1]nonane hydroperchlorate‐6,8,10‐14C3 (2) is described via a Mannich type of condensation. 4‐Thianone (3) was treated with 14C‐labelled benzylamine (14CH2) and paraformaldehyde [(H214C=O)n] in a solution of acetic acid with a small amount of concentrated HCl added for a period of six hours at reflux under nitrogen. Workup with aqueous sodium hydroxide followed by treatment with a high vacuum technique provided 7‐benzyl‐7‐aza‐3‐thiabicyclo[3.3.1]nonan‐9‐one‐6,8,10‐14C3 (4). Reduction of 4 under Wolff‐Kishner conditions with hydrazine/KOH in triethylene glycol at the boiling point of o‐xylene provided the corresponding crude amine after workup. Treatment with 60% perchloric acid (below 5°C) resulted in the formation of the title compound 2 which could be recrystallized (95% ethanol). The melting point and spectral data confirmed the structure which had a specific activity of 0.64 μCi/mg.
The synthesis of [3H] ‐ indole‐3‐carbinol, a natural anti‐carcinogen from cruciferous vegetables
Authors: Dashwood Roderick H. , Uyetake Lyle , Fong Arthur T. , Hendricks Jerry D. , Bailey George S.
Published: October 2006

Indole‐3‐carbinol is a natural anti‐carcinogen found as a glucosinolate in cruciferous vegetables such as cabbage, cauliflower and broccoli. A complete understanding of the mechanisms of anti‐carcinogenesis by this dietary inhibitor requires improved insight into the disposition and metabolic fate of indole‐3‐carbinol in vivo. Such metabolic studies have been hampered by the lack of a commercial source of radiolabelled compound. This provided the main impetus for the work reported here, the synthesis of 5‐[3H]‐indole‐3‐carbinol from 5‐bromoindole.
Synthesis of [21‐14C]‐fusarin C by enzymic demethylation and remethylation with [14C]‐diazomethane
Authors: Lu S‐J. , Li M. H. , Jeffrey A. M.
Published: October 2006

Fusarin C, a potent mutagen isolated from Fusarium moniliforme culture extracts, has been prepared radiolabeled in two steps by enzymic hydrolysis of the 21‐methyl ester group, using phenobarbital induced microsomal preparations, followed by remethylation using [14C]‐diazomethane. Yields, based upon fusarin C, were essentially quantitative and approximately 10% of the [14C]‐methyl‐nitrosourea, converted to diazomethane, reacted to yield [14C]‐fusarin C.
Synthesis of [methine‐3H]ddt and its nitro‐analog, and isotope effects in their enzyme‐catalyzed dehydrochlorination
Authors: Kurihara N. , Ikemoto Y. , Okutani S. , Clark A. G.
Published: October 2006

[methine‐3H]1,1‐Di‐(4‐chlorophenyl)‐2,2,2‐trichloroethane ([methine‐3H]DDT) and its di‐(4‐nitrophenyl) analog, both of high purity with a moderately high specific activity were prepared. Chlorobenzene was condensed with [1‐3H]1‐(4‐chlorophenyl)‐2,2,2‐trichloro‐ethanol, which had been synthesized by sodium boro[3H]hydride reduction of 4‐chlorophenyl trichloromethyl ketone. The purified [3H]DDT had a specific activity of 0.77 Ci/mmol (28.49 GBq/mmo 1). [methine‐3H]1, 1‐Diphenyl‐2,2,2‐trichloroethane was similarly synthesized and was nitrated to give [methine‐3H]1,1‐di‐(4‐nitrophenyl)‐2,2,2‐trichloroethane of 1.63 Ci/mmol (60.31 GBq/mmol). Dehydrochlorination with housefly enzyme (glutathione‐dependent DDT dehydrochlorinase) showed a remarkable isotope effect. For DDT, the observed tritium isotope effect on Vmax/Km was 11.51±0.52. For the nitro‐analog, the value was 11.3±1.2. We measured deuterium isotope effect on Vmax/Km for DDT in a competitive mode and obtained the value 4.19±0.34. Based on these values, the magnitude of intrinsic isotope effect values on DDT‐dehydrochlorination reaction was discussed.
Synthesis of [3H]‐1‐[1‐(3‐isothiocyanatophenyl) cyclohexyl]piperidine (METAPHIT), an acylating agent for phencyclidine receptors
Authors: De Costa Brian R. , Lessor Ralph A. , Thurkauf Andrew , Highet Robert J. , Jacobson Arthur E. , Rice Kenner C.
Published: October 2006

The preparation of [3H]‐labelled 1‐[1‐(3‐isothiocyanatophenyl) cyclohexyl]piperidine (METAPHIT), an electrophilic acylating agent for the phencyclidine (PCP) site is described. Synthesis of [3H]METAPHIT was accomplished in three steps starting from 1‐[1‐(3‐nitrophenyl)cyclohexyl]piperidine. Introduction of the tritium‐label in 20.6% radiochemical yield was achieved in the penultimate step.
Synthesis of (R,S)‐6H‐6‐[2‐(dimethylamino)ethoxycarbonyl]‐[6‐14C]dibenzob[b,d]pyran.HCL ([14C] FCE 20696)
Authors: Fontana Erminia , Vicario Gian Piero , Melloni Piero
Published: October 2006

A seven steps synthesis of (R,S)‐6H‐6‐[2‐(dimethylamino) ethoxycarbonyl]‐[6‐14C]dibenzo[b,d]pyran.HCl [14C]FCE 20696 employing 9‐[9‐14C]fluorenone as labelled starting material is reported. The final product [14C] FCE 20696 was obtained in an overall radiochemical yield of 31%, 97% radiochemically pure and with a specific radioactivity of 115 MBq/mmol.
Synthesis of deuterium and tritium labelled m‐aminolevamisole and levamisole
Authors: Sangster Nicholas C. , Lacey Ernest , Than Chit , Long Mervyn A.
Published: October 2006

Levamisole (LEV) is a widely used anti‐parasitic agent. In order to characterise the biochemical pharmacology of LEV in parasitic nematodes, [3H]LEV and a more active analogue [3H]m‐aminolevamisole (MAL) have been prepared. Labelling was accomplished by tritiated water exchange of MAL under acid conditions. Multiple site labelling was achieved in the positions ortho and para to the amino group of MAL. Tritiation of MAL HCl in [3H]2O was achieved at 103°C for 23 h. Crude [3H]MAL was diazotised (hydrochloric acid and sodium nitrite) and deaminated (hypophosphorous acid) to effect the synthesis of [3H]LEV. Products of both reactions were purified by preparative h.p.l.c. and characterised by h.p.l.c., t.l.c. and mass spectrometry. (Radiochemical yield was about 15% and purity >90%.) Specific activities of 39 Ci/mmol for [3H]MAL and 37 Ci/mmol for [3H]LEV were obtained.
Synthesis and NMR characterization of (15N)taurine [2‐(15N)aminoethanesulfonic acid]
Authors: Philippossian G. , Welti D. H. , Fumeaux R. , Richli U. , Anantharaman K.
Published: October 2006

The title compound was prepared in three steps with 55% overall yield starting from potassium (15N)phthalimide. The synthetic route involved reaction with 1,2‐dibromoethane, hydrolysis of the resulting N‐(2‐bromoethyl)(15N)phthalimide with HBr and treatment of the 2‐bromoethyl(15N)amine thus formed with sodium sulphite. The product was characterized by 13C, 1H and 15N NMR spectroscopy. The absolute coupling constants of 15N with the 13C nuclei and the non‐exchanging protons were determined and an unambiguous assignment of the proton signals obtained.