bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthese De Phospholipides Marques Au Carbone 14 A l'aide Du “pyrophosphate D'Enediol Cyclique”
Authors: Danan J.‐L. , Pichat L.
Published: October 2006

14C labelled phospholipid synthesis through the use of “cyclic enediolpyrophosphate”.

Ramirez's phrophosphate 1 was used in a one pot convenient synthesis of a few [1‐14C]‐acyl phospholipids. Reagent 1 was condensed with 1,2‐[1‐14C] dipalmitoyl Sn‐glycerol to the cyclic triester phosphate 4 which without isolation, was reacted with N‐tritylethanolamine, 3‐0‐benzyl Sn‐glycerol and glycerol leading to intermediates 5, 6, 7 which were deprotected by triethylamine hydrolysis and other appropriate treatments.
A convenient synthesis of 13C‐bromoform and 13C‐tetrabromomethane from 13C‐iodomethane labelling through 13:CBr2
Authors: Siegel Herbert , Seebach Dieter
Published: October 2006

Phenyldithiane 3 is methylated with 13CH3I to give, through the thioacetal 4, labelled acetophenone (5). NaOBr‐cleavage to the title compounds 1 and 2 (65 % and 76 %, respectively) and their use in the preparation of the dibromocyclopropane 6 and the dibromoolefin 7 are described.
Syntheses De γ, γ‐Dimethyl α‐Methylene‐γ‐ Butyrolactone Et d'oxa‐1 Spiro [4,5] Methylene‐3 Decanone‐2 Marquees Au Carbone‐14
Authors: Schlewer Gilbert , Stampf Jean‐Luc , Benezra Claude
Published: October 2006

14C‐labelled γ, γ‐dimethyl‐α‐methylene‐γ‐butyrolactone 1 and 1‐oxa‐Spiro [4.5]‐3‐methylene‐2‐decanone 2 have been synthesized from acetone and cyclohexanone respectively and 14C‐labelled ethyl bromomethacrylate (Réformatsky reaction). The synthesis of this last compound is also described.
Preparation of 17β‐hydroxy‐[1ξ,2ξ‐3H2]4,6‐Androstadien‐3‐one
Authors: Taylor Clinton A. , Danzo Benjamin J. , Smith Howard E.
Published: October 2006

17β‐Hydroxy‐[1ξ,2ξ‐3H2]4,6‐androstadien‐3‐one was prepared by the selective reduction of 17β‐hydroxy‐1,4,6‐androstatrien‐3‐one in benzene with tritium over 5% palladium on carbon. After purification by thin layer chromatography and high pressure liquid chromatography, the specific activity was at least 37 Ci/mmol, and the radiochemical purity was greater than 96%.
Reactions of metal carbonyl complexes. XII. Synthesis of 13C‐labelled (η6‐benzene)chromium(O) chalcocarbonyl complexes: (η6‐C6H6)Cr(13CO)3 and (η6‐C6H6)Cr(13CO)2(CX) (X = S, Se)
Authors: English Ann M. , Plowman Keith R. , Butler Ian S.
Published: October 2006

13C‐Labelled (η6‐benzene)tricarbonylchromium(0), BzCr(13CO)3 (Bz = η6‐C6H6), has been prepared in about 50% yield with greater than 90 atom% 13C‐enrichment by a multistep, photochemically‐induced exchange of the three carbonyl groups in BzCr(CO)3 with 13CO. The syntheses of the closely related, 13CO‐labelled, thiocarbonyl and selenocarbonyl derivatives, BzCr(13CO)2(CX) (X = S, Se), from BzCr(13CO)3 are also described.
Marquage Par 14C Du[(Chloro‐2‐Ethyl)‐3 Nitroso‐3 Ureido]‐1′ Tri‐O‐Acetyl‐2′,3′,4′ α,β D‐Ribopyrannose Ou R.P.C.N.U.
Authors: Moreau M. F. , Madelmont J. C. , Godeneche D.
Published: October 2006

RPCNU was labelled with 14C on three positions:

‐ On the carboxyl of the acetyl groups

‐ On the carboxyl of the acetyl groups

‐ On the urea carbonyl
Production of 13N‐labelled molecular nitrogen for pulmonary function studies
Authors: Vaalburg W. , Steenhoek A. , Paans A. M. J. , Peset R. , Reiffers S. , Woldring M. G.
Published: October 2006

A method for the production of 13NN either as a gas or as an injectable solution is described. The method is based on the 16O(p,α)13N reaction and water as target material. Following irradiation, the 13NO and 13NO are reduced to 13NH3, followed by NaOBr oxidation to 13NN. With a beam current of 1 μA and 20 min irradiation time the injectable solution contained 148 MBq (4 mCi) per ml.
The preparation of tritium and deuterium‐labelled camptothecin
Authors: Ronman Peter E. , Wani Mansukh C. , Wall Monroe E.
Published: October 2006

The synthesis of d, l, ‐12‐bromocamptothecin (2d) from camptothecin (1) is described. Reduction of the bromo derivative 2d with tritium gas in the presence of palladium on carbon afforded d, l‐camptothecin 12‐3H having a specific activity of 29 Ci/mmol. A simpler labelling procedure was subsequently discovered whereby deuterium in the presence of palladium on carbon reduced ring B of camptothecin and also exchanged the C‐5 hydrogen with deuterium. The reduced camptothecin aromatized to camptothecin in the presence of air to give deuterium incorporation in the C‐5 and C‐7 positions.
A versatile procedure for the preparation of palmitic acid‐d2 and stearic acid‐d6
Authors: Adlof R. O. , Emken E. A.
Published: October 2006

Syntheses of palmitic acid‐d2 and stearic acid‐d6 are described, the latter route also having the capability of producing methyl oleate and elaidate‐13,13,14,14‐d4 from the same synthetic sequence. Overall yields are in the range of 40 to 60%. These syntheses use tris (triphenylphosphine) ‐ chlororhodium(I) for the incorporation of deuterium. Atomic absorption spectroscopy is used to confirm that less than 70 ppb rhodium catalyst remained in the final products.
Synthesis of 14C and 3H specifically labelled 1‐benzyl‐4‐ ‐picolinoyl‐piperazine
Authors: Zólyomi G. , Budai Z.
Published: October 2006

Specifically labelled 1‐benzyl‐4‐picolinoyl‐piperazine (4) was synthetized for use in metabolism studies. Carbon‐14 was introduced both in benzyl and picolinoyl groups, and tritium in the benzyl group. By using commercial n‐butyllithium in n‐hexane, the yield of picolinic acid was improved.
A rapid and convenient method for specific 11C‐labelling of synthetic polypeptides containing methionine
Authors: Långström B. , Sjöberg S. , Ragnarsson U.
Published: October 2006

11C‐labelling of methionine residues in a synthetic peptide via the preparation of the corresponding protected, pure homocysteine peptide has been investigated. Complete deprotection of the peptide and specific methylation of the homocysteine residue can be performed in one step in liquid ammonia. As a first application of this method the synthesis of the tripeptide, Z‐Gly‐L‐Hcy (Bzl)‐Gly‐O‐Bzl, and its conversion to Gly‐Met‐Gly and the corresponding labelled Gly‐([11C]‐methyl) ‐ Met‐Gly, is reported. Starting with the protected peptide the labelling was performed in 20 ± 5 min (starting with 11CO2), yielding the labelled peptide in 92 ± 5 % radiochemical yield. Analyses and preparative LC can be performed within 6 min.
The preparation of aromatic astatine compounds through aromatic mercury compounds part II: Astatination of pyrimidines and steroids
Authors: Visser Gerard W. M. , Diemer Eduard L. , Kaspersen Frans M.
Published: October 2006

Several 211At‐astatopyrimidines (5‐At‐uracil, 5‐At‐cytosine and their nucleosides and nucleotides including DNA and RNA) have been synthesized in high radiochemical yields by reaction of 211At/I2 and the corresponding chloromercury compounds. Also some astato‐steroids (6‐At‐cholesterol and 2‐ and 4‐astatoestradiol) have been prepared by this method. The stability in vitro was determined under different conditions in comparison with the analogous iodo compounds.
3‐[11C]‐methyl‐D‐glucose, a potential agent for regional cerebral glucose utilization studies: Synthesis, chromatography and tissue distribution in mice
Authors: Kloster G. , Müller‐Platz C. , Laufer P.
Published: October 2006

3‐[11C]‐Methyl‐D‐glucose was synthetized by methylation via 11CH3I of the potassium salt of diacetone‐D‐glucose; hydrolysis of the ketal groups with HCl yields 3‐[11C]‐methyl‐D‐glucose. The radiochemical yield is 35% at a specific activity of 1.9 mCi/μmole. Synthesis time including purification by hplc is about 30 min. Up to 12.0 mCi have been obtained in injectable solution.

The tissue distribution of 3‐[11C]‐methyl‐D‐glucose was determined in mice at different times after an i.v. injection. All well‐perfused organs like lung, heart, liver, kidney and brain rapidly accumulate 3‐[11C]‐methyl‐D‐glucose. The accumulation in brain is significant: at 15 min after application it reaches 6.2% dose/g organ.
Synthesis of 1,5,9‐cyclododecatriene‐x‐14C6
Authors: Susán Alexander B. , Duncan William P.
Published: October 2006

A small‐scale synthesis of 1,5,9‐cyclododecatriene‐x‐14C6 is described. 1,3‐Butadiene‐1,4‐14C2, specific activity of 1.15 mCi/mmole, was prepared via the thermal decomposition of tetramethylene‐1,4‐14C2‐bis‐(trimethylammonium hydroxide) and immediately converted to a mixture of stereoisomers of 1,5,9‐cyclododecatriene‐x‐14C6 using a Ziegler catalyst prepared in situ. The overall radiochemical yield was 15% (based on K14CN).
3H‐labelled bilirubin and biliverdin
Authors: Hutchinson David W. , Wilkes Nicola M. , Au Hilary Y. N.
Published: October 2006

A simple method is described for the preparation of [3H]bilirubin IX‐α by the reduction of biliverdin IX‐α using sodium boro[3H]hydride. The [3H]bilirubin is obtained with a high specific radioactivity and the tritium is located at the methylene bridge (C‐10). Oxidation of the [3H]bilirubin with chloranil results in some loss of tritium from C‐10 and [3H]biliverdin is obtained.
Tritium labeled prostacyclin sodium salt
Authors: Hsi Richard S. P. , Stolle Wayne T. , McGrath James P. , Morton Douglas R.
Published: October 2006

Crystalline [11β‐3H]prostacyclin (PGI2) sodium salt (5) was prepared from prostaglandin D2 (PGD2) methyl ester (1). Reduction of PGD2 methyl ester with sodium borotritide afforded [11β‐3H]prostaglandin F2α (PGF2α) methyl ester (2a) in 57% radiochemical yield. [11β‐3H]PGF2α methyl ester was converted via (5R, 6R)‐ and (5S, 6S)‐5‐iodo‐[11β‐3H]prostaglandin I1 methyl ester (3) to [11β‐3H]‐prostacyclin methyl ester (4). Carefully controlled hydrolysis of 4 produced crystalline [11β‐3H]PGI2 sodium salt which was shown to be >95% pure by means of high performance liquid chromatographic (HPLC) analysis. The overall yield from [11β‐3H]PGF2α methyl ester to [11β‐3H]PGI2 sodium salt was 53%. [11β‐3H]PGI2 sodium salt with a specific activity of 502 μCi/mg has only limited radiochemical stability. Its radiochemical purity declined 15% after three weeks of storage at −20°C in the crystalline state.
Synthesis of 6‐substituted benzo[a]pyrene‐α‐14C derivatives
Authors: Hicks James L. , Heys J. Richard
Published: October 2006

6‐Lithiobenzo[a]pyrene was carbonated to produce benzo[a]pyrene‐6‐carboxylic‐14C acid, which was in turn used in the preparation of several derivatives. Methylation to the ester was followed by LiAlH4 reduction to 6‐hydroxymethyl‐14C‐benzo[a]pyrene. An efficient oxidation using DDQ produced the corresponding aldehyde. Direct reduction of the ester using LiAlH4 and AlCl3 produced 6‐methyl‐14C‐benzo[a]‐pyrene.
Synthesis of [16,16,17α‐2H3] estradiol and [14α,15,15–2H3] estrone of high isotopic purity
Authors: Massey Ian J. , Tökés Laszlo
Published: October 2006

The title compounds, each of high isotopic purity, were synthesized as internal standards for the mass spectral quantitation of estradiol and estrone. The [2H3] estradiol 3 was obtained from estrone (1) by alkaline H/2H exchange of the C‐16 protons and LiAl2LH4 reduction of the C‐17 keto function. The [2H3] estrone 16 was synthesized by a multistep sequence using deuterioboration of a C‐14 double bond and a three step reductive deuteration of a C‐15 keto function as the key steps for deuterium incorporation.
Synthesis of 14C‐labeled inhibitors of monoamine oxidase
Authors: Williams C. H.
Published: October 2006

The monoamine oxidase inhibitors pargyline and clorgyline have been synthesized by methylation of the appropriate secondary propargylamines, using [14C]dimethyl sulphate. This simple method should be generally applicable to other compounds of this class.
Synthesis of radioactive 11C molecules for medical research on a microscale : A theoretical and practical approach
Authors: Berger Gérard , Mazière Mariannick , Godot Jean‐Marie
Published: October 2006

It is often necessary to obtain certain 11C radiopharmaceuticals with a high specific activity (> 1000 Ci/mmole), especially when these are intended for medical purposes and are either toxic or used for “in vivo” specific receptor binding studies. The amounts of labelling agent must be very small (concentrations often below to 10−3 M) and some synthesis are difficult or impossible under these conditions.

This article shows how the specific activitry of the labelling agent A affects the synthesis yield of the radiopharmaceutical A′ in the reaction:

A specific activity increase can improve, reduce or have no effect on the yield according to the respective valuse of V1, V2, V′1, V′2.

Different ways to shift an epuilibrium unfavourabel to labelling are also given : reaction temperature, concentrations, addition of starting products, removal of final products.

The reaction kinetics are important since the half‐life of carbon 11 is 20 mn, but this parameter is a complex function of concentrations which can only be detemined by experiment. It seems however that in special cases the percentage of radioactivity incorporated in a given times is imdependent of specific activity.

The effect of impurities, which can be present in concentration of the same order of magnitude as those of the labelling agent is also discussed.

Each thereticl development is illustrated by concrete examples studied in the laboratory.

The conclusion is that theoretically it should not be impossible to synthesize strictly carrier‐free 11C radiopharmaceuticals in certain favourable cases (if it were known how to prepare such carrier‐free labelling agents).
O‐deuterio‐butanoic acid
Authors: Maskill H
Published: October 2006

A literature procedure for the preparation of O‐deuterioacetic acid from the anhydride gives substantial deuterium incorporation at C‐2 when used to prepare deuteriobutanoic acid. The enol form of butanoic anhydride is implicated as the intermediate which causes the isotopic scrambling. The required title compound was obtained by the reaction of butanoyl chloride and deuterium oxide.
An efficient synthesis of 5‐(phenyl‐13C6)‐5‐phenylhydantoin
Authors: Poupaert Jacques H. , Winand Martial , Dumont P.
Published: October 2006

A procedure is described to convert benzene‐ 13C6 into 5‐(phenyl‐ 13C6)‐5‐phenylhydantoin in 80% overall yield.
Enzymatic synthesis of 11C‐labelled S‐adenosylmethionine
Authors: Gueguen Paul , Morgat Jean‐Louis , Maziere Mariannick , Berger Gérard , Comar Dominique , Maman Michel
Published: October 2006

This article describes the radiosynthesis of 11C‐labelled S‐adenosylmethionine by an enzymatic process. This methyl donor was prepared by condensation of L‐(methyl‐11C) methionine with ATP. The synthesis and purification could be carried out in 20 minutes with a final yield of 80 %. The specific radioactivity obtained was close to 200 Ci/mmole. 6 mCi of 11C‐labelled S‐adenosylmethionine was injected in a rabbit, and its repartition followed by an opticamera.
The synthesis of disodium‐3‐amino‐1‐hydroxypropane‐1, 1‐diphosphonate‐1‐14C. (APD· 2Na)
Authors: Magnien Ernest , Shaikh Mujahid , Suh John T. , Jones Howard
Published: October 2006

Disodium‐3‐amino‐1‐hydroxy‐1, 1‐diphosphonate‐1‐14C (APD 2Na), a powerful calcium binding agent and potential drug for the treatment of Paget's Disease was synthesized. The reaction was carried out by reacting β‐alanine (1‐14C) with phosphorus acid and phosphorus trichloride in chlorobenzene. Treatment of the resultant APD with two equivalents of sodium hydroxide gave the title compound.
Synthesis and characterization of 14C polyvinylphosphonic acid
Authors: Stringer Orum D. , Charig Andrew
Published: October 2006

Ten mCi of 14C ethylene was converted to 1.16 mCi of 14C PVPA by oxidative phosphonation with phosphorus trichloride and molecular oxygen, dehydrohalogenation with triethylamine in ether, polymerization, and hydrolysis. The polymer had a specific activity of 12 uCi/mg and a radiochemical purity over 99%.
A new and efficient synthesis of monotritiomethyl iodide
Authors: Saljoughian Manouchehr , Morimoto Hiromi , Dorsky Albert M. , Rapoport Henry , Andres Hendrik
Published: October 2006

A new and efficient synthesis of high specific activity TCH2I containing one atom of tritium per molecule is reported. The precursors for this reagent, chloromethyl p‐phenylbenzoate or bis‐chloromethyl terephthalate, were prepared by the condensation of the corresponding acid chlorides with paraformaldehyde in the presence of zinc chloride. Tritiodehalogenation of the precursors with tritium gas and Pd‐C (10%) in dimethylformamide afforded the desired tritioesters. Cleavage of the esters by lithium iodide at 180°C (SN2 type reaction), or by HI at 140°C gave mono tritium labeled methyl iodide in more than 95% yield. The reaction of the latter with a number of amines yielded tritium labeled N‐methylated products readily as was shown by Radio‐HPLC. The specificity of the labeling in the final products was confirmed by tritium nmr spectroscopy.
The synthesis of 2‐14C‐N‐nitrosothiazolidine
Authors: Cragin David W. , Shibamoto Takayuki
Published: October 2006

2‐14C‐N‐Nitrosothiazolidine was synthesized with a chemical purity of 99.6%, a radio chemical purity of 99.4%, and an overall yield of 30.7%. Unlabelled N‐nitroso‐thiazolidine, synthesized using the same method, resulted in a purity of 99.85% by capillary GC and 99.7% by HPLC. Analysis of N‐nitrosothiazolidine by GC was found to require a low injection port temperature of 160°C to prevent denitrosation in the injection port. During the nitrosation of thiazolidine, if the pH was reduced below 4 with hydrochloric acid, ring hydrolysis occurred, and chlorinated disulfide compounds formed.
Synthesis of 1‐benzyl‐4‐[(5,6‐dimethoxy[2‐14C]‐1‐indanon)‐2‐yl]‐methylpiperidine hydrochloride (E2020‐14C)
Authors: Iimura Youichi , Mishima Mannen , Sugimoto Hachiro
Published: October 2006

1‐Benzyl‐4‐[(5,6‐dimethoxy[2‐14C]‐1‐indanon)‐2‐yl]‐methylpiperidine hydrochloride (1) (E2020‐14C), an acetylcholinesterase inhibitor for studying the pharmacokinetic profiles of E2020, was synthesized from 5,6‐dimethoxy[2‐14C]‐1‐indanone (2) as the labelled starting material.
Preparation of sodium 2‐mercapto‐[14C]ethanesulfonate
Authors: Jarý J. , Grossmann V. , Doležal S. , Labsk´ J.
Published: October 2006

Starting from [1‐14C]ethanol 1,2‐dibrom‐[14C]‐ethane was prepared by an usual method through [14C]‐ethylene. Sodium sulfite was alkylated by 1,2‐dibrom–[14C]ethane and the formed sodium 2‐brom‐[14C]ethane sulfonate was transferred without isolation to a labelled 2‐[(aminoiminomethyl)thio]‐[14C]ethanesulfonic acid. After purification by crystallization of the acid 2‐mercapto‐[14C]ethanesulfonic acid was prepared through guanidinium salt. After the neutralization of 2‐mercapto‐[14C]ethanesulfonic acid by sodium hydroxide the corresponding sodium salt with specific activity 0.083 μCi/mmol (0.31 MBq/mmol) was prepared.
Catalytic tritiation of splenopentine and diacetylsplenopentine via the di‐iodo‐tyrosine derivatives
Authors: Oehlke J. , Mittag E. , Klebsch H.‐J. , Niedrich H.
Published: October 2006

Tritium labelled splenopentine (Arg‐Lys‐Glu‐Val‐Tyr‐OH) and diacetylsplenopentine (Nα‐ac‐Arg‐Nα‐ac‐Arg‐Nε‐ac‐Lys‐Glu‐Val‐Tyr‐OH) were prepared by the catalytic dehalotritiation of the corresponding diiodopeptides obtained by ICl‐iodination. Under conditious which proved to be optimal in foregoing model deuterations, a specific radioactivity of about 90% of the theoretical one was achieved. The labelling result was influenced noticeably by a transfer of solvent hydrogen directly to the substrate analogously as found in the dehalodeuterations of simple amino acid derivatives.
Positron labeled phorbol ester: Synthesis method for “non‐carrier added” phorbol 13‐[1‐11C] butyrate using ketene reaction
Authors: Imahori Yoshio , Fujii Ryou , Ido Tatsuo , Hirakawa Kimiyoshi , Nakahashi Hisamitsu
Published: October 2006

A new method was developed to synthesize positron labeled phorbol esters for second messenger imaging based on a receptor binding to protein kinase C. [1‐11C]propyl ketene was produced by the pyrolytic decomposition of [1‐11C]butyric acid. This new method was made possible by the reaction of [1‐11C]propyl ketene to the hydroxyl group of phorbol under the non‐carrier added conditions. The precursor protected in the 20‐hydroxyl group of phorbol was acylated by [1‐11C]propyl ketene to the 13‐hydroxyl group producing phorbol 13‐[11C]butyrate ([11C]P13Bu). Total synthesis time was about 60 minutes and the specific activity was greater than 67 GBq/μmol (1800 mCi/μmol). [11C] P13Bu will prove to be useful ligand for PET studies due to the simple procedures required for synthesis.
Preparation of 2H‐ and 3H‐labelled carvone
Authors: Banthorpe Derek V. , Brown Geoffrey D.
Published: October 2006

(‐)‐Carvone labelled with 2H or 3H at C‐10 was prepared by two methods. The first, involving a reversible ene reaction yielded 10‐deuteriocarvone with some substitution at other reactive centres. An improvement to this route involved the decomposition of an organozinc reagent of 10‐chloro‐carvone which gave a better yield of product substituted only at C‐10. As a preliminary to a possible radioimmunoassay with the above material, four derivatives of carvone linked to bovine serum albumin were prepared.
Synthesis of 15N labelled nylon 6
Authors: Glans J. H. , Hatfield G. R.
Published: October 2006

The synthesis of 15N labelled nylon 6 by anionic polymerization of ϵ‐caprolactam is described. Labelling of this commercially important polymer should greatly enhance investigations of its morphology by techniques such as NMR, IR, and Raman spectroscopies.
High specific activity tritiated prostaglandin analogs I: Synthesis of enprostil‐[13, 14‐3H]
Authors: Parnes Howard
Published: October 2006

Partial reduction of the acetylenic precursor 1 with carrier‐free tritium gas in the presence of Lindlar catalyst gave the highly labelled cis‐allylic alcohol 2. Tritium was thus contained in the metabolically stable 13,14‐position of the lower side chain. Elaboration of 2 via a fourteen step, microscale sequence gave enprostil‐[13,14‐3H] 19 having a specific activity of 41 Ci/mmol.
Synthesis of methyl arachidonate‐17, 17, 18, 18‐d4
Authors: Adlof Richard
Published: October 2006

Methyl arachidonate (5c, 8c, 11c, 14c‐20: 4) 17, 17, 18, 18‐d4 was prepared for use in both in vivo and in vitro metabolism studies. The deuterium atoms were incorporated by deuterium gas and Wilkinson's catalyst. The tetraacetylenic acid precursor (5a, 8a, 11a, 14a‐20: 4) 17, 17, 18, 18‐d4 was synthesized by a series of Grignard coupling reactions and reduced by Lindlar catalyst and hydrogen gas to arachidonic acid‐d4. The methyl ester was prepared by diazomethane and purified by a combination of reverse phase and silver resin chromatography. The deuterated methyl arachidonate was prepared in an overall yield of ca. 11% and with an isotopic purity of ≥91%. The deuterium‐labelled tetracetylenic acid precursor and the methyl arachidonate‐d4 were characterized by 13C‐NMR.
Labelled compounds of interest as antitumour agents. Part III (1). Synthesis of 2H and 3H isotopomers of etanidazole (SR 2508)
Authors: Webb Paul , Threadgill Michael D.
Published: October 2006

Chemically and radiochemically efficient syntheses of N‐(2‐hydroxy‐2‐[2H]ethyl)‐2‐(2‐nitroimidazol‐l‐yl)acetamide and N‐(2‐hydroxy‐2‐[3H]ethyl)‐2‐(2‐nitroimidazol‐1‐yl)acetamide, isotopomers of the hypoxic cell radiosensitiser etanidazole (SR 2508), have been achieved by reduction of the corresponding aldehyde with isotopically labelled sodium borohydride. The primary kinetic deuterium isotope effect for the process is 1.5.
C‐29 tritiated β‐amyrin: Chemical synthesis aiming at the study of aromatization processes in sediments
Authors: Lohmann Françoise , Trendel Jean‐michel , Hetru Charles , Albrecht Pierre
Published: October 2006

Tritiated β‐amyrin (olean‐12‐en‐3β‐ol, 2) was synthesized in six steps, from epikatonic acid (3), with a specific activity of 550 GBq/mmole. The protracted incubation of this triterpene in a pond mud led by biodegradation to labelled aromatic tetracyclic hydrocarbons, identical with known sedimentary biomarkers.
Effects of catalyst pretreatment and additives on the hydrogen incorporation during the catalytic deuteration of N‐acetyl‐di‐iodotyrosineamide
Authors: Oehlke J. , Niedrich H. , Zöpfl H.‐J. , Franke P.
Published: October 2006

The influence of the mode of presaturating the catalyst and of different inhibiting agents on the catalytic deuteration of N‐acetyl‐3,5‐di‐iodo‐L‐tyrosineamide was investigated in order to derive conclusions for optimizing peptide tritiations. Reactions of the activated catalyst with solvent and substrate can be inhibited independently. The exchange of the catalyst‐bound deuterium against hydrogen from solvent is inhibited by the substrate itself and by addition of 1,3‐di‐chlorobenzene. The dehalogenation reaction and the unspecific exchange of carbon‐bound hydrogen of the substrate are inhibited preferably by thioglycolic acid, iodide and by the triethyl‐ammonium ion.
A convenient preparation of 2‐[15N]‐amino‐4,6‐dimethoxypyrimidine
Authors: Spencer Thomas K. , Georg Gunda I. , Aubé Jeffrey
Published: October 2006

A convenient preparation of 2‐[15N]‐amino‐4,6‐dimethoxypyrimidine using 15N‐ammonium chloride as the source of 15N is described.
Synthesis of racemic, S(+)‐ and R(‐)‐N‐[methyl‐3H]3,4‐methylenedioxymethamphetamine
Authors: Hashimoto Kenji , Hirai Katsumi , Goromaru Tsuyoshi
Published: October 2006

The synthesis of 3,4‐methylenedioxymethamphetamine(MDMA), a serotonergic neurotoxin, labeled with tritium is described. Labeling was accomplished by N‐alkylation of the free base of the corresponding desmethyl compound using [3H]methyl iodide. The compound was purified by preparative HPLC. The radiochemical yield was about 60% based on [3H]methyl iodide. The radiochemical purity was more than 95% from HPLC and TLC. Furthermore, S(+)‐ and R(‐)‐[3H]MDMA were completely separated by analytical HPLC with chiral column.
Complexes of technetium III and IV with pyrophosphate: Preparation, analysis and metabolic breakdown studies
Authors: Shafiq Y. F. , Al‐Janabi M. A. A. , Abdel‐Azeez M. A. M.
Published: October 2006

The oxidation state of technetium‐pyrophosphate (99m‐Tc PYP) reduced by SnCl2.2H2 O was determined by radiochromatography. Two different complexes were formed (complex I and complex II). The oxidation states of Tc to be III or IV or both in complex II or hydrated technetium dioxide in complex I were investigated. Formation of Tc (III)/Tc(IV)‐PYP and hydrated technetium dioxide‐PYP complexes were studied by radiochromatography and by biodistribution in mice. Experiments in animals helped to clarify the behaviour of these complexes. Thus urine obtained from one group of mice injected with 99m‐Tc‐PYP complexes wase reinjected to another group of mice. It was found that complex II excreted in the urine was not broken down while cleavage and deposition of 99m‐Tc‐species were found with complex I excreted in urine.
Synthesis of [18O]thionyl chloride
Authors: Hepburn Timothy W. , Lowe Gordon
Published: October 2006

A new synthesis of [18O]thionyl chloride has been developed which, for the first time, allows the product to be isolated in pure form.
Facile and economical preparation of [14C]‐labelled shikimic acid
Authors: Krüper Annette , Gehrke Peter , Amrhein Nikolaus
Published: October 2006

A convenient and inexpensive method for the preparation of [14C]‐labelled shikimic acid based on the photoassimilation of 14CO2 by henbane (Hyoscyamus niger L.) leaves in the presence of the herbicide glyphosate is described.

Methanolic extracts were purified by successive anion exchange, paper and thin‐layer chromatography to yield [14C]‐labelled shikimic acid of 99.5% radiochemical purity, as shown by analytical HPLC. Under the conditions employed, the rate of incorporation of 14CO2 into shikimic acid (0.7 – 17.6%) showed a positive correlation with the size of the leaf used in the incubation (3.6 ‐ 146 mg fresh weight), while the specific activity of the acid (6 ‐ 12.7 GBq/mmol) was an inverse function of the leaf size.
Regio‐ and stereo‐selective deuterium labelling of β‐cyclodextrin
Authors: Djedaïni Florence , Desalos Jacques , Perly Bruno
Published: October 2006

Reliable methods for the selective deuteration of β‐cyclodextrin are described. Kinetic studies of the proton‐deuterium exchange catalysed by Raney nickel in deuterium oxide show dramatically different behaviours of positions 2, 6 and 3 and allow selective labelling. Deuteration of protons at position 2 can be achieved by performing the exchange procedure at room temperature or preferably at 310 K. Under these conditions, no other positions are affected. At refluxing temperature, protons of the methylene group rapidly exchange and, at longer reaction times, deuteration at C3 takes place. A combination of direct and back exchange cycles affords cyclodextrins labelled on any of the sensitive positions. “Organic shift reagents” are used to assist the NMR analysis of labelled samples and have shown some stereoselectivity for deuteration of the C6 methylene group protons.
Synthesis of sodium 3‐ethyl‐7‐isopropyl‐[2‐14C]‐azulene‐1‐sulfonate
Authors: Suzaka Hiroaki , Tomiyama Tsuyoshi , Ikegami Shiro
Published: October 2006

Sodium 3‐ethyl‐7‐isopropylazulene‐1‐sulfonate1, which has been found to be a potent and chemically stable agent having anti‐inflammatory and anti‐ulcerous activity, was synthesized in14C‐labelled form by using potassium [14C]‐cyanide.14C‐Labelled1with a specific activity of 9.02 mCi/mmol was prepared in eight steps in 21.9% overall chemical yield from 3‐(t‐butyldiphenylsilyloxy)propyl tosylate10.
Synthesis of [2′‐13C]biotin
Authors: Etzel W. A. , Berger S.
Published: October 2006

[2′‐13C]Biotin was synthesized in 51% yield by reaction of the hydrolysis product of biotin, 3,4‐diaminotetrahydro‐2‐thiophenvalerianic acid, with [13C]phosgene.
Synthesis of mitomycin C labeled with mono‐tritium at the C6 ‐ methyl position
Authors: Kanda Yutaka , Akinaga Shiro , Kasai Masaji
Published: October 2006

A first preparation of mitomycin C specifically labeled with mono‐tritium at the C6‐methyl position is described. The key intermediate in the synthesis, 7,7‐ethylenedioxy‐6‐methylenemitosane (5) was made by treating 7,7‐ethylenedioxy‐6‐phenylselenomitosane (4) with meta‐chloroperbenzoic acid. Subsequent 1,4‐addition of [3H]hydride gave 7,7‐ethylenedioxymitosane labeled with tritium (6). Amination at C7 position and deacetylation of 1a‐aziridine nitrogen of 6 gave [C6‐CH3‐3H1] mitomycin C (2) with an overall yield of 15%. The specific activity of the final compound was 16.2 mCi/mmol with 13% tritium incorporation.
Preparation of 15N labeled tetranitromethane C(15NO2)4
Authors: Skawinski William , Flisak Joseph , Chung Alex C. , Jordan Frank , Mendelsohn Richard
Published: October 2006

15N labeled tetranitromethane, C(15NO2)4, was prepared from anhydrous nitric acid and acetic anhydride. A procedure for the preparation of the nitric acid from Na15NO3 is described. Tyrosine was nitrated with H15NO3 and its 15N NMR spectrum compared well with that of tyrosine nitrated with C(15NO2)4.
Synthesis of 3‐[D7]isopropylbenzo‐2‐thia‐1,3‐diazinon‐(4)‐2,2‐dioxide ([D7]‐bentazone)
Authors: Jacquemijns Marjorie , Stavenuiter Johannes F. C. , Zomer Gijsbert
Published: October 2006

[D7]bentazone (95 atom% D) was synthesized from methyl antranilate and [D7]isopropylsulfamoyl chloride. [D7]isopropylsulfamoyl chloride was prepared by treatment of [D7]isopropyl amine with chlorosulfonic acid and phosphorous pentachloride. The overall yield from [D7]isopropyl amine was 7%.
Synthese radioactive de sels d'ammonium quaternaires d'hydroxy imino methyl‐2 OU ‐4 pyridinyle par l'intermediaire de la N‐methyl formanilide‐14C. II. Marquage par 14C de l'iodure d'[hydroxyimino methyl‐2 methyl‐1 pyridinyle ou 2‐PAM Iodure et du diodure de trimethylène dioxy‐3,3′ bis [hydroxy imino methyl‐2 methyl‐1, pyridinyle] ou R‐665
Authors: Madelmont J. C. , Nicolas C. , Maurizis J. C. , Dupuy J. M. , Garrigue H. , Meyniel J. M. , Demerseman P. , Sentenac‐Roumanou H. , Veyre Et A.
Published: October 2006

The two compounds were labelled by 14C on the hydroxyimino methyl group substituted on the 2 positions of the pyridinium ring.

The convenient pyridinium lithiated intermediates were formylated with N‐methyl 14C‐formanilide. The hydroxyimino methyl groups were synthezised by reaction of the 14C‐formyl compound with hydroxylamine. For the two species alkylation of pyridine was performed with methyliodide. Radiochemical yields were 50% and 20%.
Synthesis of [119mSn]‐mesoporphyrin IX dichloride
Authors: Denissen Jon F.
Published: October 2006

Tin mesoporphyrin IX dichloride (Sn‐MPCl2) is a heme oxygenase inhibitor of current clinical interest for the treatment of neonatal hyperbilirubinemia. The synthesis of [119mSn]‐MPCl2 for drug metabolism and disposition studies is reported. [119mSn]‐MPCl2 was prepared in 60% radiochemical yield by metalation of the porphyrin nucleus of mesoporphyrin IX dihydrochloride with tin(II)‐119m acetate. The product had a specific activity of 43.4 mCi/mmol and a radiochemical purity of 99%, as determined by radio‐HPLC analysis.
Facile [14C]methane preparation using the reduction of [14C]methyl iodide by sodium borohydride
Authors: Elbert Thomas , Matucha Miroslav
Published: October 2006

[14C]Methane (440 mCi) was prepared using the reduction of [14C]methyl iodide by sodium borohydride in diglyme in quantitative yield. The diborane formed was trapped as nonvolatile 9‐BBN. [14C]Methane free of any accompanying gases was conveniently distributed into calibrated glass ampules by the aid of capillary vacuum manifold and freezing out by liquid nitrogen.
Syntheses of 14C‐labelled monoacidic metabolites of dithiopyr
Authors: Mehrsheikh Mohammad E. , Clizbe Lane A. , Singh Harbhajan , Purdum Wr
Published: October 2006

Convenient methods for the selective hydrolysis of the thioester groups of dithiopyr to the corresponding carboxylic acid are described. 2‐(Difluoromethyl)‐4‐(2‐methylpropyl)‐5‐[(methylthio)carbonyl]‐6‐(trifluoromethyl)‐3‐pyridine‐4‐14C‐carboxylic acid (2) was obtained by simple potassium hydroxide hydrolysis of 14C‐labelled dithiopyr. A more involve strategy was necessary for the preparation of the isomeric carboxylic acid 6‐(difluoromethyl)‐4‐(2‐methylpropyl)‐5‐[(methylthio) carbonyl]‐2‐(trifluoromethyl)‐3‐pyridine‐4‐14C‐carboxylic acid (3)
Regiospecific synthesis of polychlorinated dibenzofurans with chlorine‐37 excess
Authors: Chang Yoon‐Seok , Deinzer Max L.
Published: October 2006

The synthesis of regiospecifically chlorine‐37 labeled di‐ and trichlorodibenzofurans is described. The strategy for introducing a chlorine‐37 label regiospecifically has been to reduce the nitro derivative to the corresponding amine. The amine is converted to the diazonium salt with t‐butyl nitrite, and this product is converted to the final product via the Sandmeyer reaction with chlorine‐37 labeled cuprous chloride.
Radioiododestannylation. Convenient synthesis of a high affinity thromboxane A2/prostaglandin H2 receptor antagonist
Authors: Mais Dale E. , Halushka Perry V. , Naka Masao , Morinelli Thomas A. , Oatis John E. , Hamanaka Nobuyuki
Published: October 2006

Radioiodination of methyl‐7‐[(2R, 2S, 3S, 5R)‐6,6‐dimethyl‐3‐(4‐trimethylstannylbenzenesulfonylamino) bicyclo[3.1.1]hept‐2‐yl]‐5(Z)‐heptenoate with [125I] Na using a modification of the chloramine‐T method in organic solvent is simple with high yields and site specific. The product, following hydrolysis of the ester, 7‐[(2R, 2S, 3S, 5R)‐6,6‐dimethyl‐3‐(4‐[125I]‐iodobenzenesulfonylamino) bicyclo[3.1.1]hept‐2‐yl]‐5(Z)‐heptenoic acid ([125I]‐ISAP), was purified by HPLC. The high specific activity and specific binding will make the ligand a useful tool for the characterization of thromboxane A2/prostaglandin H2 receptors.
Syntheses of 18F‐labeled reduced haloperidol and 11C‐labeled reduced 3‐N‐methylspiperone
Authors: Ravert Hayden T. , Dannals Robert F. , Wilson Alan A. , Wong Dean F. , Wagner Henry N.
Published: October 2006

18F‐Labeled reduced haloperidol and 11C‐labeled reduced 3‐N‐methylspiperone were synthesized in a convenient and quantitative one step reduction from 18F‐labeled haloperidol and 11C‐labeled N‐methylspiperone, respectively. Both products were purified by semipreparative HPLC and were obtained at high specific activity and radiochemical purity.
Preparation of [123I]‐ and [125I]epidepride: A dopamine D‐2 receptor antagonist radioligand
Authors: Clanton J. A. , de Paulis T. , Schmidt D. E. , Ansari M. S. , Manning R. G. , Baldwin R. M. , Kessler R. M.
Published: October 2006

(S)‐(−)‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐[123I]iodo‐2,3‐dimethoxybenzamide (TDP 517) (proposed generic name, [123I]epidepride) is the iodine‐123 substituted analogue of isoremoxipride (FLB 457), both of which are very potent dopamine D‐2 antagonists (epidepride KD 0.024 nM). [123I]Epidepride was radioiodinated in 60–70% radiochemical yields in 35 min from the corresponding 5‐(tributyltin) derivative using Na123I with a specific radioactivity of 3000 Ci/mmol, and oxidized in situ with chloramine‐T. The aryltin precursor was prepared from non‐labelled epidepride by palladium‐catalyzed stannylation using bis(tri‐n‐butyltin) in triethylamine. Alternatively, using no carrier‐added Na125I as the radioisotope, [125I]epidepride at 2000 Ci/mmol specific radioactivity was prepared in 86% radiochemical yield and 99% radiochemical purity after purification by reverse phase HPLC in ethanolic phosphate buffer.
Synthesis of [20,21‐13C2]‐progesterone
Authors: Caballero Gerardo M. , Gros Eduardo G.
Published: October 2006

The synthesis of, [20,21‐13C2]‐progesterone (9) from androst‐4‐ene‐3,17‐dione (1) is described. Labels were introduced by two procedures, namely, condensation of 1 with K13CN and Grignard reaction of nitrile derivative 7 with [13C]‐methylmagnesium iodide. Location of labels was confirmed by 13C‐NMR spectroscopy.
Synthesis of [C6‐CH3‐14C] and [C6‐CH3‐3H3]mitomycin C
Authors: Arai Hitoshi , Kasai Masaji
Published: October 2006

A facile synthesis of the title compounds 2 and 3 is described. The key intermediate in the synthesis, 6‐demethyl‐7,7‐(ethylenedioxy)‐6‐(phenylselenenyl)mitosane (4) was synthesized in five steps from mitomycin A. Treatment of 4 with [14C]methyl iodide in the presence of K2CO3 afforded the [14C]‐labelled mitosane (5). The removal of the phenylselenenyl group of 5 and subsequent treatment of the resultant mitosane 7 with ammonia led to the desired [14C]mitomycin C (MMC) (2) with specific activity of 50 mCi/mmol. Similarly, [3H]‐labelled MMC (3) with highly specific activity of 78.4 Ci/mmol was obtained.
Synthesis of multiply deuterium‐labelled prednisone and prednisolone
Authors: Shibasaki Hiromi , Furuta Takashi , Kasuya Yasuji
Published: October 2006

We have synthesised prednisone and prednisolone labelled with four deuterium atoms at chemically stable sites ([1,19,19,19‐2H4]prednisone and [1,19,19,19‐2H4]prednisolone), starting from [1,1,19,19,19‐2H5]cortisone. The isotopic purities were demonstrated to be > 98 atom%. There were no indications of deuterium loss from the C‐19 and C‐1 positions during the synthetic sequence involving an oxidation reaction step using selenium dioxide in tert‐butanol.
Syntheses of 3H‐ and 2H‐labeled (16S)‐15‐deoxy‐16‐hydroxy‐16‐methyl‐5‐thiaprostaglandin E1 methyl esters
Authors: Sugiura Satoshi , Tanaka Toshio , Bannai Kiyoshi , Kurozumi Seizi
Published: October 2006

The syntheses of [7‐2H]‐, [7‐3H]‐, and [2,2,3,3,4,4‐2H6]‐(16S)‐15‐deoxy‐16‐ hydroxy‐16‐methyl‐5‐thiaprostaglandin E1 methyl ester (2, 3, and 4) are described. Both 7‐labeled compounds, 2 and 3, were prepared from the Δ7‐precursor (11) by treatment with in‐situ generated tributyltin deuteride and [3H]hydride, respectively. The hexa‐deuterated compound 4 was prepared starting from tetrahydrofuran‐d8
Synthesis of 14C‐labelled (S)‐(+)‐6‐(2‐chlorophenyl)‐3‐cyclopropanecarbonyl‐8,11‐ dimethyl‐2,3,4,5‐tetrahydro‐8H‐pyrido[4′,3′:4,5]thieno[3,2‐f][1,2,4]triazolo[4,3‐a][1,4]diazepine (14C‐E6123)
Authors: Miyazawa Shuhei , Okano Kazuo , Kusano Kazutomi , Tadano Kyoichi , Tanaka Shigeru , Yuzuriha Teruaki , Machida Yoshimasa , Yamatsu Lsao
Published: October 2006

14C‐Labelled (S)‐(+)‐6‐(2‐chlorophenyl)‐3‐cyclopropanecarbonyl‐8,11‐dimethyl‐2,3,4,5‐ tetrahydro‐8H‐pyrido[4′,3′:4,5]thieno[3,2‐f][1,2,4]triazolo[4,3‐a][1,4] diazepine (14C‐E6123), a platelet activating factor receptor antagonist for studying the pharmacokinetic profile of E6123, was synthesized in three steps using [1‐14C] acetyl hydrazine fumarate as the labelled starting material. The final product has high chemical and radiochemical purity with a specific activity of 53.2mCi per mmol (1.97GBq per mmol). The overall radiochemical yield is 6.0%.
Enzymatic synthesis of isotopically labelled pyrimidine deoxyribonucleotides
Authors: Frank‐Kamenetskaya  , Myasoedov N. F.
Published: October 2006

An enzymatic method is described which makes it possible to synthesize labelled pyrimidine deoxyribonucleotides from corresponding labelled ribonucleotides using the RDP‐reductase system of ether‐treated E. coli E125 cells. Ether‐treated cells have been used for the first time for preparative enzymatic synthesis of labelled biologically active compounds.
Synthesis of 1,3,5,5–tetranitrohexahydropyrimidine–2,2,4,4,6,6–d6 (DNNC–d6) and its adiol–d4 precursor using paraformaldehyde–d2 and unlabeled reaction ingredients
Authors: Shackelford Scott A.
Published: October 2006

Using commercially available paraformaldehyde–d2, the subject compounds were synthesized with unlabeled reactants and ordinary solvents. The 2,2–dinitropropane–1,3‐diol–1,1,3,3–d4 (ADIOL–d4) precursor was produced in greater than 99% isotopic purity with aqueous depolymerized paraformaldehyde–d2 and CH3NO2 in alkaline solution followed by oxidative AgNO3/NaNO2 nitration; then, ADIOL–d4 and depolymerized paraformaldehyde–d2 with t‐butylamine in methanol afforded cyclic 1,3–di–t‐butyl–5,5–dinitrohexahydropyrimidine–2,2,4,4,6,6–dδ (DBNP–d6). The 97% isotopically pure DNNC–d6 product resulted in 71% yield from an anhydrous HNO3 nitration of DBNP–d6.
Stereoselective synthesis of stable isotope‐labeled L‐α‐amino acids: Chemomicrobiological synthesis of L‐[β‐13C]‐, L‐[2′‐13C]‐, and L‐[1′15N]tryptophan
Authors: Unkefer Clifford J. , Lodwig Siegfried N. , Silks Louis A. , Hanners John L. , Ehler Deborah S. , Gibson Rowena
Published: October 2006

We have developed a stereospecific chemomicrobiological synthesis of labeled tryptophan. L‐[3‐13C]Serine, [1‐15N]‐ and [2‐13C]indole were used as precursors for the synthesis of L‐[β‐13C]‐, L‐[1′‐15N]‐, and L‐[2′‐13C]tryptophan, respectively. The labeled precursors were incorporated quantitatively into tryptophan using a strain of E. coli engineered to overproduce tryptophan synthase. Labeled indoles were prepared by the base‐promoted cyclization of appropriately labeled N‐formyl‐o‐toluide; serine was prepared biosynthetically as described previously.
Syntheses of [2‐14C] 2,5′‐anhydro‐3′‐azido‐3′‐deoxythymidine and [2‐14C] 2,5′‐anhydro‐3′‐azido‐2′,3′‐dideoxy‐5‐iodouridine: Inhibitors of human immunodeficiency virus (HIV‐1)
Authors: Lin Tai‐Shun , Liu Mao‐Chin , August E. Michael , Birks Evelyn M. , Prusoff William H.
Published: October 2006

The syntheses of [2‐14C] 2,5′‐anhydro‐3′‐azido‐3′‐deoxythymidine and [2‐14C] 2,5′‐anhydro‐3′‐azido‐2′,3′‐dideoxy‐5‐iodouridine in a one pot operation under mild conditions are described.
Use of tritiated methylborane in the synthesis of labelled primary amines
Authors: Burgos Alain , Kamenka Jean‐Marc , Rousseau Bernard
Published: October 2006

Tritiated methylborane prepared from tritium gas and methaneboronic acid was used to prepare [2‐H3]‐trans‐2‐phenylcyclopentylamine from 1‐phenylcyclopentene with a high specific activity (26Ci/mmol) in 20–40% yield.
Synthesis of [14C]‐ and [3H]‐labelled (+)‐[1R‐[1α,2α(Z),3β,4α]]‐7‐[3‐[(Phenylsulfonyl)AMINO]BICYCLO[2.2.1]HEPT‐2‐YL]‐5‐HEPTENOIC ACID, ((+)‐S‐145) AND ITS CALCIUM SALT (S‐1452)
Authors: Nagasaki T. , Watanabe F. , Katsuyama Y. , Hamada Y. , Ohtani M. , Narisada M.
Published: October 2006

(+)‐S‐145 and S‐1452, thromboxane A2 receptor antagonists, were labelled with 3H and 14C for studies on the metabolic fate and characterization of receptor binding. 3H and 14C were incorporated into the benzene ring in the phenysulfonylamide side chain with specific radioactivities of 26.4 Ci/mmol and 8.73 mCi/mmol, respectively. The common key intermediate, amine 12a was synthesized in eight steps from 4a for facile labelling.
Synthesis of a Radiotracer for Studying k‐Subtype Opiate Receptors: N‐[11C‐methyl]‐N‐(trans‐2‐pyrrolidinyl‐cyclohexyl)‐3,4‐dichlorophenylacetamide ([11C](±)U‐50488H)
Authors: Noble Glen D. , Dannals Robert F. , Ravert Hayden T. , Wilson Alan A. , Wagner Henry N.
Published: October 2006

The radiochemical synthesis of a κ‐subtype opiate receptor ligand, [11C](±)U‐50488H, was accomplished either in two steps or by direct methylation with [11C]iodomethane. The radiotracer was purified using reversed phase semipreparative HPLC. The average specific activity was 1830 mCi/μmole (calculated at the end‐of‐synthesis; EOS) for the direct methylation and 2140 mCi/μmole EOS for the two‐step one‐pot synthesis. The average time of synthesis including formulation was approximately 22 minutes for the direct methylation and 27 minutes for the two‐step one‐pot synthesis.
Enzymatic synthesis of isotopically labelled purine deoxyribonucleotides
Authors: Frank‐Kamenetskaya  , Myasoedov N. F.
Published: October 2006

An enzymatic method is described which makes it possible to synthesize labelled purine deoxyribonucleotides from corresponding labelled purine ribonucleotides using the RDP‐reductase system of ether‐treated E. coli E125 cells.
Further investigation on the radiosynthesis of α‐[11C]methyl‐tryptophan
Authors: Suehiro Makiko , Ravert Hayden T. , Wilson Alan A. , Scheffel Ursula , Dannals Robert F. , Wagner Henry N.
Published: October 2006

Improved procedures for the radiosynthesis of α‐[11C]methyltryptophan and α‐[11C]methyl‐tryptophan methyl ester were studied. Following α‐deprotonation of tryptophan methyl ester benzaldimine with LDA, 60 – 80% of no carrier added [11C]iodomethane was incorporated in 5 minutes at 27 – 30°C. After HPLC purification, radiochemically pure α‐[11C]methyl‐tryptophan or its methyl ester was produced with minimum chemical contamination from tryptophan. The [11C]methyl‐tryptophan synthesized, however, was found to be a racemate.
Improved synthesis of [11C]methylaminobenzovesamicol
Authors: Keith Mulholland G. , Jung Young‐Woon
Published: October 2006

An efficient two‐step synthesis of the potential cholinergic neuronal mapping tracer [11C]methylaminobenzovesamicol (MABV) is described. A tert‐butoxycarbonyl protecting group was used to activate the aniline nitrogen of aminobenzovesamicol toward [11C]methyl iodide methylation under basic conditions. Following labeling, the protecting group was removed by brief acid treatment and the final product was purified by normal phase HPLC. The decay corrected yields of MABV are in the range of 30‐70 %, based on 11CO2, with a specific activity of 0.5‐1.5 Ci/ μmol and synthesis time of less than 45 minutes. This new route makes clinical scale doses of this interesting compound available for human positron emission tomography studies.
HPLC isotope effects and macrocycles: The case of echinocandin B
Authors: Jones Allen N. , Simpson Robert E. , Jenkins Herbert J.
Published: October 2006

Echinocandin B was catalytically reduced with hydrogen, deuterium, or tritium. HPLC analysis of the products showed that the labeled analogs exhibited a significant isotope effect relative to the unlabeled parent, with the elution order tritiated < deuterated < hydrogenated. Mass spectral data and specific activity measurements indicated label incorporation exceeded saturation of the double bonds. Proton nmr of the deuterated compound indicated labeling was confined to the aliphatic side chain. A model compound, anilinosteareamide, prepared from the linoleic precursor by reduction with hydrogen or deuterium, incorporated the label only in the aliphatic chain, and also exhibited an isotope effect. This helped confirm that label incorporation in only the fatty acid portion of tetrahydroechinocandin B was sufficient to cause the observed isotope effect.