bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of carbon‐14 labeled 1,4‐benzodiazepines. IV. Carbon‐13 and carbon‐14 labeled 8‐chloro‐1‐(2‐dimethylamino)ethyl‐6‐phenyl‐4H‐s‐triazolo[4,3‐a][1,4]‐benzodiazepine tosylate
Authors: Hsi Richard S. P. , Stolle Wayne T.
Published: October 2006

Carbon‐13 and carbon‐14 labeled forms of the title compound have been prepared from the correspondingly labeled forms of 8‐chloro‐1‐methyl‐6‐phenyl‐4H‐s‐triazolo[4,3‐a][1,4]benzodiazepine (3)

Alprazolam is the generic USAN name for this compound.

. A modified and more convenient version of the previously reported procedure for preparing 3 is described.
Preparation of biphenyl‐2,2′,3,3′,5,5′,6,6′‐2H8
Authors: Clark Alice M. , Davis Patrick J. , Smith Robert V.
Published: October 2006

Biphenyl‐2,2′,3,3′,5,5′,6,6′‐2H8 was prepared from biphenyl‐d10. Initial bromination of biphenyl‐d10 followed by hydrogenolysis of the 4,4′‐dibromobiphenyl‐d8 with lithium aluminum hydride gave the desired product in 40% overall yield.
A novel synthesis of α‐N‐methyl‐14C‐DL‐asparagine by generation of methylamine‐14C insitu
Authors: Tsou Hwei‐Ru
Published: October 2006

A method is described by which methylamine‐14C is qenerated from its hydrochloride by N,N‐diisopropylethylamine in the presence of maleamic acid to produce the title compound in high yield.
Synthesis of 4‐amino‐3,2′ ‐dimethylbiphenyl‐3‐methyl‐14C and 4‐amino‐2′‐methylbiphenyl‐2′‐methyl‐14C
Authors: El‐Bayoumy Karam , Hecht Stephen S.
Published: October 2006

The syntheses of 4‐amino‐3,2′‐dimethyl‐biphenyl‐3‐methyl‐14C, a potent carcinogen and mutagen, and 4‐amino‐2′‐methylbiphenyl‐2′‐methyl‐14C, an analogue having weaker activity, are described. In both cases, label was introduced with Cu14 CN.
Application of spin labeling to drug assays. I. Synthesis of 2,2,6,6‐tetramethylpiperidin‐4‐one‐1‐oxyl‐15N‐d16
Authors: Yost Yul , Polnaszek Carl F. , Mason Ronald P. , Holtzman Jordan L.
Published: October 2006

Spin labeled drugs can be utilized for immunoassays and determining the fraction of free drug in serum. To improve the sensitivity we have synthesized triacetonamine‐15N‐d17 by cyclization of phorone‐d14 with 15ND3. Phorone‐d14 was obtained by condensation of acetone‐d6. Triacetonamine‐15N‐d17 gave Tempone‐15N‐d16, a nitroxide with just two absorption peaks on the ESR spectrum, whereas Tempone gives 3 peaks. The contribution to line width of methylene and methy1 hydrogens of Tempone is evaluated by appropriate substitution of protium with deuterium.
Synthesis of 14C‐labelled metoprolol
Authors: Chaudhuri Naba K. , Ball Thomas J.
Published: October 2006

The synthesis of 14C‐labelled metoprolol, a new antihypertensive drug is described. Starting from p‐bromoanisole and 14CO2, 14C‐labelled p‐methoxyphenylethyl alcohol was prepared by the following sequence of reactions: MeO‐C6H4‐Br→ MeO‐C6H4‐14COOH→ MeO‐C6H4‐14CH2OH→ MeO‐C6H4‐14CH2Cl→ MeO‐C6H4‐14CH2‐CN→ MeO‐C6H4‐14CH2‐COOH → MeO‐C6H4‐14CH2‐CH2OH. Heating with 47% HBr gave [14C]‐p‐hydroxyphenylethyl bromide which on treatment with methanol under alkaline condition was converted into [14C]‐p‐hydroxyphenylethyl methyl ether. Reaction with epichlorhydrin followed by isopropylamine gave [14C]‐metoprolol.
14C‐labelling of optically active fenvalerate, (S)‐α‐cyano‐3‐phenoxybenzyl (s)‐2‐(4‐chlorophenyl)‐3‐methylbutyrate (II)
Authors: Kanamaru Hiroshi , Kamada Takeshi , Nakatsuka Iwao , Mohri Zen‐Ichi , Okamura Taeko , Yoshitake Akira
Published: October 2006

(S)‐α‐Cyano‐3‐phenoxybenzyl (S)‐2‐(4‐chlorophenyl)‐3‐methylbutyrate (fenvalerate Aα), an optically active insecticide, was labelled with carbon‐14 individually at the benzyl ring (1a) and the chlorophenyl ring (1b) for use in metabolic studies. Ullmann reaction of 3‐methylphenol‐14C6 (2) with bromobenzene followed by oxygen oxidation gave 3‐phenoxybenzoic‐14C6 acid (4). Reduction of 4 followed by potassium dichromate oxidation of the alcohol (5) gave 3‐phenoxybenzaldehyde‐14C6 (6). Condensation of 6 with (S)‐2‐(4‐chlorophenyl)‐3‐methylbutanoyl chloride and sodium cyanide afforded fenvalerate A‐(benzyl‐14C6), which on optical resolution gave 1a in 29% yield from 2. Isopropylation of 4‐chlorophenyl‐14C6‐acetonitrile (9) followed by hydrolysis gave 2‐(4‐chlorophenyl‐14C6)‐3‐methylbutyric acid which on optical resolution gave the (S)‐acid (12). Esterification of the acid with α‐cyano‐3‐phenoxybenzyl bromide yielded fenvalerate A‐(phenyl‐14C6), which was resolved to give 1b in 9% yield from 9.
High specific activity [phenyl‐3h]benzylpenicillin N‐ethylpiperidine salt
Authors: Rosegay Avery
Published: October 2006

The N‐ethylpiperidine salt of [3H]penicillin G (31 Ci/mmole) was prepared and stored in acetone solution at −15°. The radiochemical purity, as determined by reverse isotope dilution assay, decreased about 12% over a period of one month, less than that expected for an aqueous solution.
Deuteration of the racemate and the (2S)‐(+)‐enantiomer of the antiarrhythmic agent disopyramide, 4‐diisopropylamino‐2‐(2‐pyridyl)‐2‐phenylbutyramide
Authors: Nelson Wendel L. , Rees Janine A. , Hulinek Sandra J.
Published: October 2006

Deuteration of disopyramide, 4‐diisopropylamino‐2‐(2‐pyridyl)‐2‐phenylbutyramide, was accomplished in an excess of 2H2SO4 at 125–135°C. Incorporation of 2‐4 atoms of deuterium occurs with 65% recovery of disopyramide. At higher temperatures (150°C) greater incorporation of deuterium occurs, but substantial decomposition reduces the recovery of disopyramide to 25%.
Synthesis of adenylyl imidodiphosphate‐β,γ‐15N
Authors: Reynolds Mark A. , Oppenheimer Norman J. , Kenyon George L.
Published: October 2006

Adenylyl imidodiphosphate, specifically 15N labelled in the β,γ‐bridging nitrogen position, was synthesized in 5% overall yield from 15NH3.
Synthesis of 1‐pyrenyloxirane‐3,6,8‐3H1
Authors: McCaustland Daniel J. , Susàn Alexander B. , Wiley James C.
Published: October 2006

The syntheses of 1‐pyrenyloxirane‐3,6,8‐3H1, 7, and its precursor, pyrene‐1,3,6,8‐3H1, 4, are described. The synthesis pathway includes a novel preparation of 4 from 1‐pyrenyllithium and tritiated water in theoretical yield.
Preparation of 2‐iodomorphine for use in radioimmunoassay
Authors: Mason P A , Law B , Ardrey R E
Published: October 2006

A method is described for the preparation of 125iodomorphine. The structure of this compound was confirmed by synthesis of 127iodomorphine and subsequent mass spectral studies. 125Iodomorphine has proved to be chemically very stable and has been shown to be bound avidly by a morphine antiserum. It should, therefore, prove to be very useful for the development of a morphine radioimmunoassay.
The synthesis of four specifically deuterated trans‐4‐octenes
Authors: Shaw G. John
Published: October 2006

trans‐4‐Octene‐1,1,1‐2H3; −2,2‐2H2; −3,3‐2H2 and −4‐2H1 have been synthesized. The electron impact mass spectra and isotopic enrichment of these compounds have been measured and are reported.
Tritium isotope effect in birch keductions
Authors: Egli Peter
Published: October 2006

D‐2‐Aminophenylacetic acid (1) (phenylglycine, PG) was subjected to a Birch reduction in the presence of tritiumion. A substantial, but relatively low isotope effect, kH/kT = 3.51, was found for the reduction reaction. The resulting D‐2‐amino‐[3,6‐3H](1,4‐cyclohexadien‐1‐yl)acetic acid (2) (dihydrophenylglycine, DHPG) aromatized rapidly by a secondary radio‐decomposition to afford mainly P[3H]G, resulting in the predicted loss of half the tritium. When a carbon‐14 label was used, the DHP[14C]G aromatized about seven times faster than DH[3H]PG normalized to the same specific activity, when stored as a solid. This difference is in good agreement with the ratio predicted based on the difference in decay energies for the two isotopes.
Synthesis of deuterium labeled C19‐Δ16 steroids
Authors: Thompson R. H. , Pearson A. M.
Published: October 2006

Deuterium labeled forms of 5α‐androst‐16‐en‐3‐one, 3α‐hydroxy‐5α‐androst‐16‐ene, 3β‐hydroxy‐5α‐androst‐16‐ene, 3β‐hydroxy‐5, 16‐androstadiene and 4, 16‐androstadien‐3‐one were prepared to serve as internal standards in quantitative analysis of C19‐Δ16 steroids by mass spectrometric reverse isotope dilution. In general, the methods used employed deuterium exchange of activated hydrogens adjacent to carbonyl carbons followed by reaction steps which isolated the newly incorporated deuterium. Removal of any remaining exchangeable deuteriums was the final step in each reaction sequence.
Synthesis of optically active deuterium labelled serine and glycylserine derivatives
Authors: Kovacs J. , Jham G. , Hui K. Y.
Published: October 2006

Optically active α‐deuterated serine dipeptide active ester derivatives were prepared to study the racemization mechanism. N‐Acetyl‐O‐benzyl‐DL‐serine, 1, was converted to 5(4H)‐oxazolone 2 and deuterated with CH3‐COOD in α‐position. 5(42H)‐Oxazolone 3 was converted to Z‐(α2H)‐L‐Ser(Bzl)‐OH

The following abbreviations are used: benzyloxycarbonyl = Z; tert‐butyloxycarbonyl = Boc; benzyl = Bzl; pentachlorophenyl = Pcp; dicyclohexylcarbodiimide = DCC; dicyclohexylurea = DCU, tetrahydrofuran = PHF; thin layer chromatography = TLC

7, after opening the 5(42H)‐oxazolone ring with D2O, removal of the N‐acetyl group, treatment with carbobenzoxy chloride and resolution with (+)‐α‐phenylethylamine. Pentachlorophenyl ester 8 of 7 was converted to Z‐Gly‐(α2H)‐L‐Ser(Bzl)‐OPcp, 10, after removal of carbobenzoxy group by catalytic hydrogenation. The deuterium content of the intermediates was determined by mass spectrometry.
Isolation of (−)‐menthol‐14C and (+)‐neomenthol‐14C
Authors: Haut Stephen A , Core Margaret T.
Published: October 2006

Uniformly labelled (−)‐menthol‐14C and (+)‐neomenthol‐14C were isolated and purified from the oil of peppermint plants grown in a 14CO2 chamber by preparative high performance liquid chromatography. This procedure is much simplier than previous methods and allows for large amounts of labelled oil to be processed.
The synthesis of 7‐chloro‐1‐methyl‐5‐phenyl‐1, 3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one‐5‐14C and 7‐nitro‐1‐methyl‐5‐(2′‐fluorophenyl)‐1, 3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one‐5‐14C
Authors: Kaegi H. H. , Burger W. , Bader C. J.
Published: October 2006

Two benzodiazepines, Diazepam and Flunitrazepam, labeled with carbon‐14 in position 5 of the diazepine ring have been synthesized. Use of a condensation between iminochlorides and 14C‐benzonitriles, followed by exhaustive methylation of the resulting quinazolines and hydrolyses is described. This sequence of reactions allows the preparation of the intermediate o‐methylamino‐benzophenones in good yields.
An investigation of the kinetics of formamidine sulfinic acid (FSA) degradation in the preparation of technetium‐99m radiopharmaceuticals
Authors: Jette D. C. , Scott J. R. , Sitarz W.
Published: October 2006

Technetium‐99m glucoheptonate complex was prepared using formamidine sulfinic acid (FSA) as a reducing agent. The fraction of technetium which was complexed to glucoheptonate remained at less than 20 percent for the first 10 minutes. After 20 minutes, the complexed fraction was greater than 95 percent and remained at this level after 24 hours. The lag phase was attributed to the kinetics of the base catalyzed degradation of FSA to urea and bisulfite. The overall rate of FSA degradation was determined and found to be dependent on the concentration of base and the initial concentration of FSA. The rate of production of one of the degradation products, urea, was also measured and found to be dependent on the concentration of base, but independent of the initial FSA concentration. A reaction scheme for the degradation of FSA was proposed and the reaction rate constants for the products of this reaction were determined.
Preparation of [15‐3h] gibberellin‐A3
Authors: Lischewski Manfred , Adam G.
Published: October 2006

The cyclobutane compounds 2, 3, 4 or 5, which represent in position‐15 functionalized gibberellin derivatives, reacted with 3H2O under mild alkaline conditions in a retroaldol‐like cleavage to give diacetyl[15‐3H]gibberllin‐A3‐7‐aldehyde (6) and the isomeric compound 7.

In respect of a second possibility of 15‐tritiation, diacetyl‐GA3‐7‐aldehyde (1) was irradiated with UV‐light in benzene/3H2O to form diacetyl [15 α‐3H] GA3‐7‐aldehyde (6a).

Oxidation and deacetylation of 6 afforded [15‐3H]gibberellin‐A3(8).
Synthesis and purification of carbon‐14 labelled 1, 1‐hexamethylene‐bis [5‐(4‐chlorophenyl)biguanide] (chlorhexidine), ‘Hibitane’
Authors: Burns J.
Published: October 2006

Two syntheses of [14C] chlorhexidine (‘Hibitane’) with the label specifically incorporated in two separate molecular positions are described. Ring labelled chlorhexidine prepared from p‐chloro[U‐14C]aniline was obtained with a molar specific activity of 27.9 mCi/mmol. Chain labelled material, where the 14C label was incorporated in the 1 and 6 positions of the hexamethylene bridge, was prepared from [1, 6 14C]‐adiponitrile, with a molar specific activity of 11.5 mCi/mmol. Several methods of purification are described.
Synthetic heparinoids labelled with 125I and 35S
Authors: Sederel L. C. , Kolar Z. , Van Der Does L. , Bantjes A.
Published: October 2006

The labelling of a water‐soluble synthetic polyelectrolyte, having anticoagulant activity, has been studied. The polyelectrolyte is derived from cis‐1,4‐polyisoprene and contains N‐sulfate and carboxylate groups. [125I]‐Iodination of the polyelectrolyte, using the Chloramine‐T method and an electrolytic method, resulted in a [125I]‐labelled polyelectrolyte from which release of the label occurred. Resulfation of a partially desulfated polyelectrolyte with a [35S]‐sulfur trioxide trimethylamine complex resulted in a [35S]‐labelled polyelectrolyte which showed no release of the label.
Deuterium exchange in sesamol
Authors: Hill Richard K. , Vaidya Niteen A. , Morton Gerald H.
Published: October 2006

Trifluoroacetic acid‐catalyzed exchange of sesamol in 2H2O results in rapid exchange of H‐6 and slower exchange of H‐2. The deuterium atoms introduced are retained during conversion to the methyl and allyl ethers.
75Se‐labelled bile acid analogues
Authors: Monks R. , Thomas I. L.
Published: October 2006

The synthesis of several 75Se‐labelled bile acid analogues* is described in which selenium‐75 replaces a carbon methylene group at different positions in the C‐17 side‐chain. Procedures for the synthesis of necessary nonradioactive intermediates are included. Some results for the organ distribution of the compounds in rats are given. 23‐[75Se] selena‐25‐homocholic acid and its glycine and taurine conjugates show particularly good properties for the study of the enterohepatic circulation of bile acids.
Direct incorporation of [11C]carbon dioxide for labeling bioactive molecules. An application to [11C] labeled tamoxifen
Authors: Ram Siya , Spicer Leonard D.
Published: October 2006

A one‐pot synthesis of [11C] labeled tamoxifen has been developed via reductive carboxylation. In this approach, [11C]CO2 is reacted with the N‐trimethylsilyl derivative of desmethyltamoxifen, followed by in situ sodium bis (2‐methoxyethoxy)aluminum hydride reduction, to afford impure [11C] labeled tamoxifen, which, on purification over a basic alumina‐silica gel column, provided pure [11C] tamoxifen in excellent radiochemical yield (65% to 84%) and radiochemical purity (>99%). The specific activity of [11C]tamoxifen was 250–400 Ci/mmol at the end of bombardment.
Synthesis and labelling with 18F of an MK 801 analogue: [18F]5‐(β‐fluoruethyl)‐10,11‐dihydro‐5H‐dibenzocycloheptene‐5,10‐imine
Authors: Denis A. , Crouzel C.
Published: October 2006

The 5‐(β‐fluoro)ethyl analogue 1 of MK 801 2 was synthesized and labelled with 18F in order to visualize the NMDA receptors by positron emission tomography. A tosyloxy precursor 3 was synthesized in 8 steps from dibromodibenzosuberone; the nucleophilic substitution of the tosyl group of 3 by the K18F/Krytofix 2,2,2 complex in CH3CN gave [18F] 1 in 25% radiochemical yield with a specific activity of 40 GBq/μmol (1 Ci/μmol).

The major excitatory amino acids in mammalian brain CNS, L.glutamate and L. aspartate, have a neurotoxic activity mediated through excitatory synaptic receptors such as N‐Methyl‐D‐Aspartate (NMDA) receptor subtype. These excitotoxic amino acids have been implicated in several brain damages associated with epilepsy, anoxia‐ischemia and hypoglycemia (1). MK 801 [(+)5‐methyl‐10,11‐dihydro‐5H‐dibenzo‐cycloheptene‐5,10‐imine] 2 is a potent and non‐competitive antagonist of NMDA (2). MK 801 was shown, in animal models, to protect against hypoxic‐ischemic damage and NMDA neurotoxicity (3, 4). These results may have important implications for the treatment in man of stroke and neurodegenerative disorders. In order to visualize the NMDA receptors by positron emission tomography, the synthesis and the labelling with fluorine 18 (β+, t½ = 110 min) of the 5‐(β fluoro(ethyl 1 analogue of MK 801 2 was undertaken (Scheme I).
The synthesis of isotopically labeled retinoids
Authors: Liebman Arnold A. , Burger Walter , Malarek David H. , Serico Lucia , Muccino Richard R. , Perry Clark W. , Choudhry Satish C.
Published: October 2006

Retinyl acetate (4a) has been prepared with a tritium label at the C‐11 and C‐12 positions by partial reduction of oxenin (1) with tritium gas followed by acetylation and rearrangement. Specific activities of up to 40 curies/mmole have been attained. By alkaline hydrolysis, retinol (5) has been obtained and derivatized as one of several retinyl esters or has been oxidized to all‐trans retinoic acid (6) having equally high specific tritium activities. From beta ionone (12), 13‐cis retinoic acid (10) has been elaborated in a variety of isotopically labeled forms. A key reaction in the sequence, the Wittig coupling of the triphenylphosphonium derivative of vinyl beta ionol (15a‐c) and the butenolide, 5‐hydroxy‐4‐methyl‐2(5H)‐furanone (8), provides access to 13‐cis retinoic acid and its 4‐oxo metabolite labeled with either isotopic hydrogen or carbon.
Studies on hindered phenols. III. Synthesis of (±)‐5‐[4‐(6‐hydroxy‐2, 5, 7, 8‐tetramethylchroman‐2‐yl‐methoxy) benzyl]‐5‐14C‐thiazolidine‐2, 4‐dione (14C‐labelled CS‐045)
Authors: Yoshioka T. , Aizawa Y. , Kanai T. , Fujita T. , Kawai K.
Published: October 2006

A synthetic procedure for producing (±)‐5‐[4‐(6‐hydroxy‐2, 5, 7, 8‐tetramethylchroman‐2‐ylmethoxy) benzyl]‐5‐14C‐thiazolidine‐2, 4‐dione (14C‐labelled CS‐045) is described. The radiolabel is introduced using [5‐14C] thiazolidine‐2, 4‐dione, as shown in the scheme.
Synthesis of α‐ and γ‐tocopherols selectively labelled with deuterium
Authors: Hughes L. , Slaby M. , Burton G. W. , Ingold K. U.
Published: October 2006

Four deuterium‐substituted α‐tocopherols (dideutero‐RRR, nonadeutero‐ambo, nonadeutero‐all‐rac and undecadeutero‐all‐rac) and a dideutero‐RRR‐γ‐tocopherol have been synthesized for use in studies of the biokinetics, bioavailability and metabolism of vitamin E.
Synthesis of L‐6‐[123I]iodo‐m‐tyrosine a potential spect brain imaging agent
Authors: Adam Michael J. , Ponce Yolanda Zea , Berry Joffre M.
Published: October 2006

L‐6‐[123I]Iodo‐m‐tyrosine was synthesized by the direct iodination of L‐m‐tyrosine with [123I]‐NaI and Chloramine‐T. The product was purified by reverse phase HPLC to give the final product in 57% radiochemical yield with a radiochemical purity of greater than 97%.
The radiosynthesis of nca [O‐methyl‐11C]viqualine, through an N‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites
Authors: Pascali Claudio , Pike Victor W. , Turton David R.
Published: October 2006

Viqualine, {4‐[3‐[3(R)‐ethenyl‐4(R)‐piperidinyl]propyl]‐6‐methoxyquinoline}, has been labelled in the O‐methyl position with no‐carrier‐added (nca) carbon‐11 (t1/2 = 20.4 min; β+ = 99.8%) to provide a potential radioligand for PET studies of 5HT re‐uptake sites. Direct treatment of desmethyl‐viqualine with nca [11C]iodomethane gave [O‐methyl‐11C]viqualine as only a minor product. NMR data suggested that the dominant product is that from the [11C]alkylation of the competing piperidino‐nitrogen. Protection of this nitrogen with the trityl group, followed by treatment with nca [11C]iodomethane in dimethyl sulphoxide with sodium hydroxide as base, and then rapid deprotection by mild acid hydrolysis gave nca [O‐methyl‐11C]viqualine as the main crude product (27% radiochemical yield, decay‐corrected from [11C]iodomethane). Radiochemically and chemically pure nca [O‐methyl‐11C]viqualine was obtained by work up on C18 Sep‐pak followed by reverse phase HPLC. The radiosynthesis, including final formulation for i.v. administration, takes 56 min after producing the carbon‐11 as [11C]carbon dioxide by the 14N(p,α)11C reaction. This radiosynthesis illustrates the potential utility of the trityl group for the protection of nitrogen in rapid carbon‐11 radiochemistry.
Synthesis of deuterium labelled lorazepam
Authors: Köves G. J.
Published: October 2006

Synthesis of 2H3‐lorazepam was achieved by modification of literature procedures for the unlabelled drug. The key step in the seven step procedure was the initial one where upon selective exchange of 2‐amino‐5,2′‐dichloro‐benzophenone was obtained in deuterated acids. Purifications were carried out by preparative HPLC. The 2H3‐lorazepam is suitable for use as an internal standard in GC‐MS‐NICI‐SIM quantitative analysis in forensic case work.
Preparation of bromine‐77 labelled monoclonal anti‐hPLAP antibody using chloramine‐T
Authors: Lambert Fabienne , Slegers Guido , Goethals Patrick
Published: October 2006

A tumor‐associated monoclonal antibody, named 7E8 and raised against human placental alkaline phosphatase (hPLAP), is labelled with bromine‐77 by means of chloramine‐T. The paper describes optimum radiobromination conditions resulting in 34% radiochemical yield of labelled antibody with more than 90% immunoreactivity.
Asymmetric hydroboration‐oxidation of alkenes by means of deuterium or tritium labelled asymmetric monoalkylboranes
Authors: Burgos Alain , Kamenka Jean‐Marc , Moustier Anne‐Marie , Rousseau Bernard
Published: October 2006

(2‐(1,3‐Dithianyl))myrtanylborane (MDBH2), a stable asymmetric monoalkylborane, was converted into deuterated or tritiated analogues used to prepare enantiomeric labelled alcohols from 1‐phenylcyclopentene with a high isotopic enrichment (90–95% for deuterium; 86–89% for tritium) and a high asymmetric induction (80% ee for deuterium; 75% ee for tritium).
High specific activity steroids I: 17α‐ethynylestradiol‐[9,11‐3H] and norethindrone‐[9,11‐3H]
Authors: Parnes Howard , Shelton Emma J.
Published: October 2006

We report herein the first high specific activity tritium labelled synthesis of the widely used oral antifertility agents ethynylestradiol (5) and norethindrone (9). These substances were prepared at a specific activity of 54 Ci/mmol, a figure which is 48 and 377 times greater than any previously described preparations of (5) and (9) respectively. Microscale conditions were developed for all the steps in the sequence, including the Birch reduction (1), so that the initially high level of enrichment usually achieved in the reduction of Δ9(11)‐estradiol 3‐methyl ether was retained in the final products.
Synthesis and separation of 3‐O‐Methyl‐2‐ and 6‐[18F]‐fluorodopa
Authors: Adam Michael J. , Jivan Salma
Published: October 2006

3‐O‐Methyl‐2‐ and 6‐[18F]‐fluorodopa were synthesized in 8% radiochemical yield by the direct fluorination of a protected L‐dopa derivative with [18F]‐acetyl hypofluorite. The 2‐ and 6‐fluoro isomers were separated and purified by reverse phase HPLC.
Synthesis of [3H]pinoline, an endogenous tetrahydro‐ß‐carboline
Authors: Callaway J. C. , Morimoto H. , Gynther J. , Airaksinen M. M. , Williams P. G.
Published: October 2006

Pinoline (6‐methoxy‐1,2,3,4‐tetrahyro‐9H‐pyrido[3,4‐b]indole) is an endogenous ß‐carboline thought to be synthesized in the pineal gland from serotonin. It is a strong inhibitor of MAO‐A and can displace [3H]citalopram from the 5‐HT uptake site on human platelets in nM concentrations. The hydrochloride salt of 6‐MeO‐DHßC (6‐methoxy‐1,2‐dihydro‐9H‐pyrido[3,4‐b]indole), also a new compound, was synthesized as the immediate precursor to the title compound.
Synthesis of a radiotracer for studying serotonin uptake sites with positron emission tomography: [11C]McN‐5652‐Z
Authors: Suehiro Makiko , Ravert Hayden T. , Dannals Robert F. , Scheffel Ursula , Wagner Henry N.
Published: October 2006

The highly potent serotonin (5‐HT) uptake blocker, McN‐5652‐Z (trans‐1,2,3,5,6,10b ‐ hexahydro ‐ 6 ‐ [4 ‐ (methylthio)phenyl] pyrrolo ‐ [2,1‐a]‐isoquinoline) was labeled with 11C for studying serotonin uptake sites using positron emission tomography (PET). [11C]McN‐5652‐Z was synthesized by S‐methylation of the normethyl precursor with [11C]iodomethane in DMF at 30 ‐ 35° C. The radiosyntheses including purification by HPLC and formulation for injection were completed in an average of 16 minutes following the end of bombardment (E.O.B.) with an overall radiochemical yield of 12%. The average specific activity determined at the end of synthesis (E.O.S.) was approximately 4250 mCi/μmole; this corresponds to approximately 7350 mCi/μmole at E.O.B. [11C]McN‐5655‐Z, a less potent blocker, was also prepared by the same procedure.
Synthesis of [N‐C3H3]‐racemic‐trans‐1‐phenyl‐3‐dimethylamino‐6‐chloro‐7‐hydroxy‐1,2,3,4‐tetrahydronaphthalene (PAT‐6)
Authors: Wyrick Steven D. , Booth Raymond G. , Myers Andrew M. , Kula Nora S. , Baldessarini Ross J.
Published: October 2006

The biological function of the sigma receptor in the central nervous system is not well understood at the present time. Once thought to be an opiate receptor, the sigma receptor has now been shown to have a neuromodulatory effect upon the synthesis of dopamine in the striatal nerve terminal. A novel sigma agonist, racemic‐trans‐1‐phenyl‐3‐dimethylamino‐6‐chloro‐7‐hydroxy‐1,2,3,4‐tetrahydronaphthalene, PAT‐6, has demonstrated the greatest potency of any compound tested to date as a sigma agonist in stimulating the synthesis of dopamine in vitro and may be functioning at a novel sigma receptor subtype. The synthesis of tritiated PAT‐6 at high specific activity is described herein. This labeled ligand was prepared for use in radioreceptor binding studies in order to identify the putative sigma receptor subtype responsible for mediation of the stimulatory effect on in vitro dopamine synthesis.
Synthesis of [3H]‐VUF 4576; A new radiolabelled Ca2+‐antagonist
Authors: Caldirola P. , Timmerman H.
Published: October 2006

The new radiolabelled [3H]‐VUF 4576 has been prepared by an easy procedure using commercially available C3H3I. The new radiolabelled ligand [3H]‐VUF 4576 belongs to a subclass of prenylamine analogues which interfere with calcium regulated pathways. The compound has been synthesized in order to study the interaction of other compounds with these mechanisms and in particular the site of action of this subclass of calcium entry blockers and calmodulin antagonists.
Synthesis of N‐[11C]‐methyl‐L‐DOPA
Authors: Horti Andrew , Ravert Hayden T. , Dannals Robert F. , Wagner Henry N.
Published: October 2006

The radiochemical synthesis of N‐[11C‐methyl]‐L‐DOPA was accomplished by N‐methylation of the methyl and ethyl esters of L‐N‐tert‐butyl‐oxycarbonyl‐[β‐(3,4‐dimethoxyphenyl)] alaninate with [11C]iodomethane using sodium hydride in tetrahydrofuran and deprotection of the N‐methyl intermediate with hydriodic acid. A catalytic influence of Kryptofix on the methylation reaction was observed. Using the ethyl ester precursor, the average specific activity at the end‐of‐synthesis was 972 mCi/μmole. The synthesis was completed in an average of 45 minutes following the end‐of‐bombardment.
Synthesis of [N‐trideuteromethyl] labelled E‐doxepin
Authors: Adamczyk Maciek , Fishpaugh Jeffrey R. , Johnson Donald
Published: October 2006

A deuterium analog of doxepin was synthesized by the reduction of an N‐doxepin carbamate with lithium aluminum deuteride.
Neuropeptides labelled with 35S
Authors: Kaspersen Frans M. , van Nispen Jan W. , Sperling Eric M. G. , Vader Jan F.
Published: October 2006

Methionine and cysteine containing peptides can be labelled with 35S by coupling of 35S‐cysteine or 35S‐methionine with a large excess of suitably protected peptide precursors. This is illustrated for [pGlu4, Cyt6]AVP‐(4‐9), β‐endorphin‐(5‐17) and the ACTH‐fragment‐analogue Org 2766. Using HPLC as final purification the peptides are obtained in radiochemical yields of about 5% and radiochemical purities between 90‐97%. However the specific activities obtained are much lower than the specific activities of the starting 35S‐amino acids.
Preparation of 9‐cis‐retinoic acid [11,12‐3H(N)] by photochemical isomerization
Authors: Dawson Marcia I. , Hobbs Peter D. , Cameron James F. , Rhee Sung W.
Published: October 2006

All‐trans‐Retinoic acid [11,12‐3H(N)] was photochemically isomerized using a fluorescent source to afford a mixture of isomeric retinoic acids, from which 9‐cis‐retinoic acid[11,12‐3H(N)] was isolated by reversed‐phase HPLC. The identity of 9‐cis‐retinoic acid [11, 12‐3H2] was confirmed by coinjection with the unlabeled acid.
Exchange labelling strategies for tritiated steroids
Authors: Simmonds Alan J
Published: October 2006

A number of commonly used tritium exchange procedures for steroids are described. Reference is also made to other available methods.
Convenient preparation of Boc‐L‐[4‐15N]asparagine and ‐[5‐15N]glutamine for application in peptide synthesis
Authors: Lankiewicz Leszek , Grehn Leif , Ragnarsson Ulf
Published: October 2006

The title compounds have been prepared by a simple and economical procedure from the corresponding Bocprotected α‐benzyl esters and [15N]ammonia with N,N′‐carbonyldiimidazole as coupling agent. Catalytic hydrogenolysis furnished both labelled products in high overall yields suitable for synthetic work.
Synthesis of [1′,3′,4′‐3H3]4‐(5′,6′,7′,8′‐tetrahydro‐5′,5′,8′,8′‐tetramethyl‐2′‐anthracenyl)benzoic acid for binding studies of retinoic acid receptors
Authors: Dawson Marcia I. , Hobbs Peter D. , Rhee Sung W. , Morimoto Hiromi , Williams Philip G.
Published: October 2006

[1′,3′,4′‐3H3]4‐(5′,6′,7′,8′‐Tetrahydro‐5′,5′,8′,8′‐tetramethyl‐2′‐anthracenyl)benzoic acid (specific activity 64 Ci/mmole) was synthesized by bromination of ethyl 4‐(5′,6′,7′,8′‐tetrahydro‐5′,5′,8′,8′‐tetramethyl‐2′‐antracenyl)benzoate, followed by reductive debromination by tritium gas in the presence of 10% palladium on carbon and hydrolysis. 1H and 3H NMR spectroscopy was used to establish tritium at 1′,3′,4′‐tetrahydroanthracenyl ring positions.
Synthese de la [15N]‐cysteamine
Authors: Lagoueyte Catherine , Subra G. , Bonnet P. A. , Fernandez J. P. , Roman V. , Fatome M. , Chapat J. P.
Published: October 2006

The synthesis of the radioprotector [15N]‐cysteamine from [15N]‐glycine is described. Cysteamine is labelled by 15N in order to study its interaction with phospholipidic membranes by 15N NMR.
Synthesis of 17α‐[(E)‐2‐[125I]iodoethenyl]androsta‐4,6‐dien‐17β‐ol‐3‐one, an active‐site‐directed photoaffinity radiolabel for androgen‐binding proteins
Authors: Cruz Pablo J. Diaz , Smith Howard E. , Danzo Benjamin J. , Clanton Jeffrey A. , Mason N. Scott
Published: October 2006

The active‐site‐directed photoaffinity radiolabel for androgen‐binding proteins, 17α‐[(E)‐2‐[125I]iodoethenyl]androsta‐4,6‐dien‐17β‐ol‐3‐ one, was prepared by reaction of 17α‐[(E)‐2‐tributyltin(IV)ethenyl]androsta‐4,6‐dien‐17β‐ol‐3‐one with carrier added sodium iodide‐125 in the presence of hydrogen peroxide and acetic acid. Purification by HPLC gave the radiolabeled steroid in 52% radiochemical yield with a specific activity of 27 Ci/mmol and 100% radiochemical purity.
211At‐labelling of polymer particles for radiotherapy: Synthesis, purification and stability
Authors: Larsen Roy H. , Hassfjell Sindre P. , Hoff Per , Alstad Jorolf , Olsen Eivind , Vergote Ignace B. , de Vos Laure N. , Bjørgum Jon , Nustad Kjell
Published: October 2006

Cyclotron‐produced 211At was distilled from a Bi metal target and coupled to N‐succinimidyl‐3‐(trimethylstannyl)benzoate. The resulting N‐succinimidyl‐3‐(211At)astatobenzoate was thereafter coupled to aminated monosized polymer particles with a diameter of 1.8 μm. The total time elapsed from the end of the cyclotron irradiation until the final product was prepared was about 2.5 hours. From 23 to 51% of the target activity at the end of bombardment was measured in the final conjugate. Solid‐liquid extraction purification of the astatinated intermediate, using Sep‐pak columns (Waters), gave more reproducible yields in the final conjugation step. The 211At‐labelled particles were incubated with fetal calf serum, human serum and human full blood at room temperature. The 211At activity on the particles was measured before and after three times washing at 4, 24 and 48 hours. The stability was not significantly different from 100% for all media and for all time points. This indicates that 211At‐labelled particles can be stable under in vivo conditions, and may thereby be a promising agent for intracavitary radiotherapy on freefloating cancer cells or surface fixed cells.
A facile and improved synthesis of 17α‐{2‐(E)‐[1 2 5 I]‐iodovinyl}‐19‐nortestosterone, a no‐carrier‐added ligand for progesterone receptor analyses
Authors: Damodaran Kalyani M. , Epperly Michael W. , Pillai K. M. R. , Bloomer William D.
Published: October 2006

Strategies for human breast cancer therapy using 125I‐labeled steroid hormones are clinically attractive in light of the estrogen dependence of and progestogen receptor involvement in many cancers and the favorable microdosimetry resulting from 125I decay. We have synthesized the no‐carrier‐added progesterone receptor ligand 17α‐{2‐(E)‐[125I]‐iodovinyl}‐19‐nortestosterone (E‐125IVNNT) by a simple and high yielding method, and determined its uptake and specific progesterone receptor binding in vitro using T47D human breast carcinoma cells. The ligand was prepared by [125I]‐iododestannylation of 17α‐[2‐(E)‐tri‐n‐butylstannylvinyl]‐19‐nortestosterone (E‐TBSVNNT) by using the rare iodinating agent [125I]‐sodium iodide/ferric sulfate in mixed dichloromethane‐water solvent. Cell binding assays demonstrated that E‐125IVNNT binding to T47D breast carcinoma was specific and saturable with an affinity for the progesterone receptor 10‐fold greater than that of 3H‐R5020.
Synthesis of [123I]tert‐butyl 8‐iodo‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo[1,5‐a][1,4]benzodiazepine 3‐carboxylate, a potential SPECT imaging agent for diazepam‐insensitive (DI) benzodiazepine receptors
Authors: He Xiao‐Shu , Matecka Dorota , Lee Kan Sam , Gu Zi‐Qiang , Rice Kenner C. , Wong Garry , Skolnick Phil , De Costa Brian R.
Published: October 2006

[123I]tert‐Butyl 8‐iodo‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo [1,5‐a][1,4]benzodiazepine 3‐carboxylate ([123I]3), a high affinity and selective radioligand for the diazepam insensitive (DI) benzodiazepine receptor was synthesized in 2 steps from tert‐butyl 8‐bromo‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo[1,5‐a][1,4]benzodiazepine 3‐carboxylate (4). A key step in the synthesis of this potential SPECT imaging agent utilized (Ph3P)3Pd mediated stannylation of 4 with (Bu3Sn)2 to the corresponding 8‐tributyltin derivative 5. Iododestannylation of 5 with no carrier added [123]NaI in aqueous ethanolic CH3CO3H furnished [123I]3 (85%) in greater than 98% radiochemical purity following TLC purification.
Synthesis of [35S]phosphorothionate insecticides : The example of [35S] fenthion
Authors: Dias Marylène , Mornet René , Kotoujansky Alain
Published: October 2006

A general method for the synthesis of [35S]phosphorothionates is proposed, based on the example of [35S]fenthion. This consists of reacting molecular 35S with the corresponding phosphites which are easily prepared from commercial precursors.
Synthesis and biological evaluation of iodine‐125 iodocaramiphen. A potential M1 muscarinic imaging agent for SPECT
Authors: McPherson Daniel W. , Knapp F. F. (Russ) , Hudkins Robert L.
Published: October 2006

Iodocaramiphen (2) is a selective muscarinic antagonist which binds in vitro with high affinity and selectivity to the M1 subtype of the muscarinic receptor. We report the synthesis of iodine‐125 labeled iodocaramiphen ([125I]‐2) via a tributylstannyl intermediate (3) in 50% radiochemical yield with a specific activity greater than 1000 mCi/μmol. Biodistribution studies in female Fischer rats demonstrated that [125I]‐2 had significant cerebral localization (0.7% injected dose/gram) at 60 minutes post injection. The uptake of activity washed out rapidly from the brain, however, and did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors. In addition, preinjection with (±)‐QNB (5 mg/kg) blocked uptake of approximately 25% of the injected radiolabel in the brain at 2 hours. The non‐selectivity of 2 toward muscarinic receptors in vivo may result from the metabolism of 2 by various esterases or the affinity of 2 for sigma sites in the brain.
A convenient method for cyanation of aromatic iodo compounds
Authors: Carr Richard M , Cable Karl M , Wells Guy N , Sutherland Derek R
Published: October 2006

A variety of [13C]‐labelled aromatic nitriles have been prepared in good yield from iodoaromatic substrates. Cyanation was achieved by reaction of aryl iodides with a mixture of potassium [13C]‐cyanide and copper (I) iodide in an aprotic solvent at high temperature. The use of pre‐prepared carbon‐labelled copper (I) cyanide was therefore obviated.
A facile synthesis of [15N4]‐octamethylporphyrin
Authors: Kogan Marcelo , Valasinas Aldonia
Published: October 2006

In order to obtain an efficient and reproducible synthesis of [15N4]‐octamethyl porphyrin for solid state CP‐MAS NMR studies, a synthesis of the outlined compound was achieved. Thus, by condensation of [15N2]‐5,5′‐dicarboxy‐3,4,3′,4′‐tetramethyldipyrrylmethane with [15N2]‐5,5′‐diformyl‐3,4,3′,4′‐tetramethyldipyrrylmethane in ethanol‐hydrochloric acid, pure [15N4]‐octamethylporphyrin was obtained in 46% yield.
Synthesis of platinum‐195m radiolabelled cis‐diammine(1,1‐cyclobutanedicarboxylato) platinum(II) of high radionuclidic purity
Authors: Kawai Kenichi , Tanaka Yoshiko , Nakano Yukihiro , Ehrlich Wilhelm , Akaboshi Mitsuhiko
Published: October 2006

An experimental method is described for the synthesis of 195mPt‐radiolabeled cis‐diammine(1,1‐eyclobutanedicarboxylatio) platinum(II) (carboplatin). 10 mg of 95 % enriched 194 PT was irradiated for 75 h in the hydraulic conveyer of KUR at a thermal neutron flux of approx.8.15 × 1013 n'cm−2'sec−1, and the 195mPt‐radiolabeled carboplatin was synthesized and purified using HPLC (column; C18‐ODS). The chemical yield was higher than 59.1 %, its chemical purity was greater than 99.3 %, the radionuclidic purity was nearly 100 % and the specific activity was 6.0 MBq, mg−1 carboplatin.
Synthesis of high specific activity 17α‐cyanomethyl‐17β‐hydroxy‐[14α,15α‐3H]estra‐4,9‐dien‐3‐one
Authors: Droescher P. , Röomer J.
Published: October 2006

An improved synthesis of the tritium labelled form of the new pharmacon DIENOGEST is described. The [14α,15α‐3‐H]DIENOGEST was obtained with a specific activity of 51 Ci/mmol and a radiochemical purity > 98%.
Preparation of n‐butoxy(13C2‐acetic) acid, 1‐n‐butoxy‐2‐hydroxy (13C2‐ethane), (n‐butoxy‐2′,2′,3′,3′,4′,4′,4′‐d7)acetic acid, and 2‐(n‐butoxy‐2′,2′,3′,3′,4′,4′,4′‐d7)ethanol
Authors: Pribish James R.
Published: October 2006

(n‐Butoxy‐2′,2′,3′,3′,4′,4′,4′‐d7)acetic acid (1) and 2‐(n‐butoxy‐2′,2′,3′,3′,4′,4′,4′‐d7)ethanol (2) have been prepared in high yield from n‐butanol‐2,2,3,3,4,4,4‐d7. n‐ Butoxy(13C2‐acetic) acid (3) and 1‐n‐butoxy‐2‐hydroxy(13C2‐ethane) (4) have also been synthesized using bromoacetic‐13C2 acid as the source of labelled carbon. The main complication in the development of the process was partial conversion of butoxyacetic acid to butyl butoxyacetate during GC analysis, which hampered evaluation of trial reactions.
Synthesis of [2‐11C]‐6,7‐dichloro‐2,3‐dihydroxyquinoxaline and evaluation of its in in vivo distribution in rat with PET
Authors: Thorell Jan‐Olov , Stone‐Elander Sharon , Ingvar Martin , Eriksson Lars
Published: October 2006

A method for labelling 6,7‐dichloro‐2,3‐dihydroxyquinoxaline (DCQX) in position 2 with carbon‐11 is presented. Diethyl [1‐11C]oxalate was synthesized in a two‐step, microwave‐assisted procedure from no‐carrier‐added [11C]cyanide and was reacted with 4,5‐dichloro‐1,2‐phenylenediamine in sulfuric acid at 150°C for 10 min. [2‐11C]DCQX, isolated by semi‐preparative HPLC, was > 99% radiochemically pure with a specific activity ranging between 19 ‐ 26 TBq/mmol. The total time of synthesis was 45–55 min and the isolated, decay‐corrected yields were on the order of 10%, based on the trapped [11C]cyanide. A PET study of its biodistribution after intravenous injection in a male rat revealed that the extraction of [2−11C]DCQX across the intact blood‐brain barrier was ⩽ 2%.
Synthesis of 3,5,6‐trichloropyridin‐2‐ol‐2,3,4,5,6‐13C5‐N; a metabolite of O,O‐diethyl‐O‐(3,5,6‐trichloro‐2‐pyridyl)‐phosphorothioate (chlorpyrifos)
Authors: Nomura Glenn S. , Patterson Donald G.
Published: October 2006

A stable isotope‐labelled analog of 3,5,6‐trichloropyridin‐2‐ol has been synthesized. 3,5,6‐Trichloropyridin‐2‐ol‐2,3,4,5,6‐13C5‐15N was synthesized in a copper catalyzed cyclization from trichloroacetyl chloride‐1,2‐13C2 and acrylonitrile‐1,2,3‐13C3‐15N.
The synthesis of 3,4‐2H2‐3Z‐hexenal and 6,6,6‐2H3‐3Z‐hexenal
Authors: Fielder Simon , Rowan Daryl D.
Published: October 2006

6,6,6‐2H3‐3Z‐Hexenal (3b) has been prepared in 89% yield and in greater than 94% purity by the oxidation of 6,6,6‐2H3‐3Z‐Hexen‐1‐ol (2b) with the Dess/Martin periodinane (1) in fluorotrichloromethane (freon 11). Use of the freon solvent greatly improved the recovery of this volatile aldehyde. Similarly the oxidation of 3,4‐2H2‐3Z‐hexen‐1‐ol (5) yielded 3,4‐2H2‐3Z‐hexenal (6) in a 92% isolated yield with a purity of greater than 99%. 3,4‐2H2‐3Z‐Hexen‐1‐ol (5) was prepared in 87% by the catalytic deuterogenation of 3‐hexyn‐1‐o1 (4) in an improved synthetic procedure.
Syntheses of colchicine and isocolchicine labelled with carbon‐11 or carbon‐13
Authors: Kothari Paresh J. , Finn Ronald D. , Larson Steven M.
Published: October 2006

The syntheses of isotopically labelled (−)‐10‐[11C/13C]‐colchicine and (−)‐9‐[11C/13C]‐ isocolchicine have been achieved from the reaction of (−)desmethylcolchicine with [11C/13C]‐iodomethane. The radiolabelled compounds, (−)‐10‐[11C]‐colchicine (11C‐n‐colchicine) and (−)‐9‐[11C]‐isocolchicine (11C‐i‐colchicine), were isolated by reversed phase HPLC. The total synthesis time was approximately 60 minutes for both radiolabelled compounds with an average specific activity of 240 mCi/μmol calculated to EOB. Utilizing a similar synthetic strategy, we also report the synthesis of milligram quantities of the carbon‐13 enriched compounds and the magnetic resonance signal assignment for (−)‐9‐[13C] isocolchicine.
Synthesis of 14C‐labelled hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX), 2,4,6‐trinitrotoluene (TNT), nitrocellulose (NC) and glycidylazide polymer (GAP) for use in assessing the biodegradation potential of these energetic compounds
Authors: Ampleman Guy , Thiboutot Sonia , Lavigne J. , Marois A. , Hawari J. , Jones A. M. , Rho D.
Published: October 2006

Within the framework of an R & D project on bioremediation of soils contaminated with energetic compounds, the biodegradation of energetic products such as hexogen (RDX), trinitrotoluene (TNT), nitrocellulose (NC) and glycidyl azide polymer (GAP) is under study. Microcosm assays must be performed with radioactive carbon‐14 labelled products in order to follow the biodegradation process. 14C‐RDX was prepared by nitration of hexamethylenetetramine (HMTA) according to the Hale process. 14C‐ring and methyl labelled TNTs were synthesized according to the Dorey and Carper procedure. 14C‐cellulose was synthesized from 14C‐glucose by Acetobacter xylinum. Nitration of the 14C‐cellulose yielded 14C‐nitrocellulose. 14C‐glycidyl azide polymer was obtained by polymerization and azidation of 14C‐epichlorohydrin (ECH) which was synthesized from 14C‐glycerol. Hydrochlorination of 14C‐glycerol and epoxidation of the resulting 14C‐1,3‐dichloro 2‐propanol yielded 14C‐ECH. The syntheses of these 14C‐labelled explosives are described in this paper.
Synthesis of (1,213C)‐2‐chloroethyl phenyl sulfide
Authors: Taber Douglass F. , Wang Yanong
Published: October 2006

Incorporation of a double 13C label into the mustard 2‐chloroethyl phenyl sulfide 2 is straightforward, but analysis is complicated by 13C‐13C coupling. An alternative is reported, in which the ease of scrambling of sulfur mustards is used to advantage to prepare precisely 50% (1, 2‐13C) enriched 2, with each carbon of the ethyl chain labelled to provide optimal signal to noise in the 13C spectrum.
A convenient method for enzymatic synthesis of radiolabelled glucose‐1,6‐bisphosphate
Authors: Nielsen Tom Hamborg , Wischmann Bente , Møller Birger Lindberg
Published: October 2006

A convenient method to synthesize radiolabelled glucose‐1,6‐bisphosphate (Glc‐1,6‐P2) of high specific activity and in a high yield is reported. The method is based on enzymatic formation of glucose‐6‐P from glucose and ATP using hexokinase. The labelled glucose‐6‐P is then converted to Glc‐1,6‐P2 through an equilibrium reaction catalyzed by phosphoglucomutase. The two enzymatic steps and TLC separations necessary to afford radiochemically pure Glc‐1,6‐P2 can be completed in one day. The outlined experimental procedure details the synthesis of [33P]Glc‐1,6‐P2 evenly labelled at the carbon 1 and the carbon 6 position. However the commercial availability of γ‐33P and γ‐32P labelled ATP and of glucose labelled with 3H, 14C and 13C provides the option to label glucose‐1,6‐bisphosphate with any of these isotopes.
Rapid synthesis of [18F]SR46349B, a potent and selective 5‐HT2 receptor antagonist
Authors: Tan Pingzhong , Fowler Joanna S. , Ding Yu‐Shin , Schlyer David J.
Published: October 2006

F‐18 labeled SR46349B, a highly potent and selective 5‐HT2 receptor antagonist, was synthesized as a potential radioligand for PET studies of brain 5‐HT2 receptors. Nucleophilic aromatic substitution of trans‐1‐(2‐nitrophenyl)‐3‐(4‐methoxymethoxyphenyl)‐2‐propenone (10) with NCA [18F]fluoride in the presence of potassium carbonate and kryptofix‐222, followed by HCl hydrolysis, gave F‐18 labeled 12, which was purified by a novel combination of C‐18 Sep‐Pak and silica column chromatography. Subsequent condensation of [18F]ketone 12 with Me2NCH2CH2ONH2 gave a mixture of [18F]SR46349B and its geometric isomer, which was separated by high performance liquid chromatography. The three step hot synthesis of [18F]SR46349B required 170 min. and gave a specific activity of 1140 Ci/mmol, 5% radiochemical yield (EOB) and 96% radiochemical purity.
Synthesis of labelled [13C6]testosterone and [13C5]19‐nortestosterone
Authors: Joubert Cécile , Beney Chantal , Marsura Alain , Luu‐Duc Cuong
Published: October 2006

The condensation of ethyl acetoacetate‐13C4 and ethyl bromoacetate‐13C2 afforded, in seven steps, (1,2,3,4,5‐13C5) 5‐(diethylphosphono)‐2‐pentanone ethylene ketal 9. The reaction of this labelled compound with 7‐[[(1,1‐dimethylethyl)‐dimethylsilyl]oxy]‐1,6,6a,7,8,9,9a, 9b‐octahydro‐6a‐methyl‐[6aS‐(6aa,7a,9aβ,9ba)] cyclopental[f][1]benzopyran‐3 (2H)‐one 13 gave the benzindenone 14 which was converted to (1,2,3,4,10,19‐13C6)testosterone 17 then, into (1,2,3,4,10‐13C5) 19‐nortestosterone 18 by a reductive alkylation method.
Synthesis of [4,6‐3H]‐2‐pyridone and [3H]‐RS‐91309
Authors: De Keczer Steve , Pames Howard
Published: October 2006

We describe herein, a novel synthesis of the previously unreported compound, 4,6‐dibromo‐2‐pyridone (3) and its use in the preparation of [3H]‐RS‐91309, a potassium channel modulator. This key intermediate, (3), was reduced with carrier free tritium gas to furnish [4,6‐3H]‐2‐pyridone (9) having a specific activity of 50 Ci/mmole. Condensation of (9) with epoxide (10), followed by elaboration of the resulting chromene methyl group of (12) gave [3H]‐RS‐91309 (14) whose specific activity was also 50 Ci/mmole. This chemistry, as well as the solution of several microscale related stoichiometry problems is discussed.