bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a novel radioiodinated glucose derivative with interaction to hexokinase
Authors: Magata Yasuhiro , Saji Hideo , Ohmomo Yoshiro , Tanaka Chiaki , Konishi Junji , Yokoyama Akira
Published: October 2006

Development of an 123I‐labeled glucose derivative that interacted with hexokinase was attempted. By introducing a benzene ring into the glucosamine molecule, we were able to secure a radioiodinated compound, N‐iodobenzoyl‐D‐glucosamine (BGA), with enhanced stability. As a result, a non‐competitive inhibitory agent on the hexokinase‐regulated phosphorylation reaction was achieved. The inhibitory action and lipophilic property of this novel compound were closely related to an amide bond in its structural configuration. Moreover, on investigating the biodistribution in mice, although this 125I‐labeled compound did not display any uptake into the brain, it demonstrated rapid clearance from the blood with high systemic stability. From the above findings, it is highly possible to develop a clinically feasible 123I‐labeled radioligand that can monitor the quantitative changes and biodistribution of hexokinase.
Synthesis of [14,15,17,17,18,18‐2H6]‐leukotriene B4
Authors: Tsikas Dimitrios , Fauler Joachim , Frölich Jürgen C.
Published: October 2006

Incubation of [14,15,17,17,18,18‐2H6] leukotriene A4 obtained by hydrolysis of chiral [14,15,17,17,18,18‐2H6] leukotriene A4 methylester with human monocytes resulted in the formation of [14,15,17,17,18,18‐2H6] leukotriene B4 (d6‐LTB4) and its trans isomers 6‐trans‐d6‐LTB4 and 12‐epi‐6‐trans‐d6‐LTB4 in high isotopic purity (99.4 % 2H). d6‐LTB4 was separated from its trans‐isomers by reversed‐phase high‐performance liquid chromatography and identified by gas chromatography mass spectrometry. d6‐LTB4 is shown to be a useful internal standard for gas chromatographic mass spectrometric analysis of LTB4 in biological matrix.
Synthesis of a tritium labeled tetrafluoro‐substituted aryl azide photoaffinity labeling agent for chloride channels. Application of [3H]‐sodium borohydride‐cobalt chloride to tritium labeling
Authors: Branchini Bruce R. , Adams Elizabeth W. , Egan Laura A. , Murtiashaw Martha H.
Published: October 2006

5‐Nitro‐2‐[N‐3‐(4‐azido‐2,3,5,6‐tetrafluorophenyl)‐propylamino]‐benzoic acid (FAzNPPB), a photoaffinity analog of the potent epithelial chloride channel blocker 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB) has been prepared in five steps from commercially available 4‐amino‐2,3,5,6‐tetrafluorobenzonitrile. The main feature of this synthesis was the use of NaBH4‐CoCl2 to convert an aryl‐substituted alkenyl nitrile precursor to the corresponding alkyl amine. The feasibility of this approach and the stoichiometry were developed by model work with cinnamonitrile. Using sodium borotritide‐cobalt chloride, [3H]‐FAzNPPB (specific activity 13.9 mCi/mmol, radiochemical purity >99%) was prepared in three steps from (E)‐4‐amino‐2,3,5,6‐tetrafluorocinnamonitrile.
An efficient method for following the enzymic reactions involved in camphor biosynthesis in cinnamomum camphora by use of GC‐MS and regiospecifically deuteriated substrate
Authors: Ohta Shinji , Yamamitsu Tohru , Suga Takayuki
Published: October 2006

An efficient method has been developed to follow the enzymic reactions involved in the biosynthesis of camphor in Cinnamomum camphora (camphor tree) by use of [5,5‐2H2]geranyl diphosphate as a substrate and GC‐MS with selected ion monitoring. Borneol and camphor biosynthesized in the enzymic reactions gave a base peak due to the deuterium‐containing ion in its EI mass spectrum. It is possible to detect 1.5 ng of the biosynthesized borneol and camphor per injection into the GC‐MS. This method enabled us to differentiate easily the biosynthesized camphor from the endogenous camphor and it is a facile and sensitive technique to determine the amount of the biosynthesized camphor.
Synthesis of D‐(‐)‐[1,7‐13C2]shikimic acid
Authors: Cho Hyeongjin , Heide Lutz , Floss Heinz G.
Published: October 2006

The chemical synthesis of 99% enriched D(‐)‐[1,7‐13C2]shikimic acid from [1,2‐13C2]acetate in 25% overall yield is described. A two‐carbon phosphonate synthon was prepared from [1,2‐13C2]acetate and used in the shikimate synthesis of Fleet and coworkers.
Synthesis of tritiated tripeptides and their very simple purification procedures
Authors: Angelini G. , Sparapani C. , Margonelli A.
Published: October 2006

The complete reaction pathway (five steps) for the syntheses of tritiated [CBZ‐Pro‐*Leu‐TrpOH] 7 (POL‐443) and [Pyr‐*Leu‐TrpOMe] 5 (POL‐509) starting from tritiated *Leu‐[3, 4, 5‐3H(N)] is described. The products 5 and 7 are obtained with high level of chemical and radiochemical purity and in good total yield (70% for 5 and 60% for 7) (1). The use of the “Solid Phase Extraction” procedure made the purification and recovery steps very simple and effective with no isotopic exchange.
Solid‐phase catalytic isotope exchange of alkylxanthines with gaseous tritium
Authors: Kaminski Ju. L. , Akulov G. P. , Patokina N. A. , Rosenberg S. G.
Published: October 2006

The results of the synthesis of 11 different tritiated alkylxanthines by solid‐phase catalytic isotope exchange are described. 3H‐NMR analysis of the labelled compounds shows that in contrast to liquid‐phase isotope exchange the tritium label is incorporated not only in the C‐8 (H) position, but also in the alkyl groups. The fraction of radioactivity in an alkyl group depends on the nature and position of this group.
Synthesis of carbon‐14 and tritium analogues of the phospholipid antitumor agent SDZ 62‐834 zi
Authors: Kinder Frederick R. , Tang Yui S. , Sunay Ustun B.
Published: October 2006

2‐[[Hydroxy[[tetrahydro‐2‐[(octadecyloxy)methyl]‐2‐furanyl)]methoxy]phosphinyl]oxy]‐N,N,N‐trimethylethanaminium hydroxide inner salt (SDZ 62‐834 zi) was synthesized with carbon‐14 at the furn‐2 position from dimethyl malonate‐[14C]. In addition, SDZ 62‐834 zi was also synthesized with tritium at the furan 3 and 4 positions by catalytic tritiation of 2,5‐dihydro‐2,2‐furandimethanol.
The enantiospecific synthesis of [5‐2H]‐epi‐shikimic acid and of (6R) [6‐2H]‐, (6S) [6‐2H]‐ and [6‐2H2] shikimic acid
Authors: Zamir Lolita O. , Nguyen Cong‐Danh , Li Shu Wen , Nikolakakis Anastasia , Sauriol Françoise
Published: October 2006

The enantioselective synthesis of [5‐2H]‐5‐epi‐shikimic acid starting from commercially available L‐shikimic acid has been accomplished in this work. The introduction of the stable isotope was facilitated by an enzymic reduction of a ketone. An interesting stereospecific enolisation was also observed during this reaction resulting in partial deuteration of the 6‐equatorial position. In addition, the enantioselective syntheses of methyl (6R) [6‐2H]‐, and (6S) [6‐2H] shikimate are described. The procedure is an adaptation of a reported(1) enantiospecific synthesis of shikimic acid, with the inclusion of an enzymic reduction step.
Synthesis of 2‐deoxy‐2‐[18F]‐fluoro‐β‐mannosyl [18F]‐fluoride as a potential imaging probe for Glycosidases
Authors: McCarter John D. , Adam Michael J. , Withers Stephen G.
Published: October 2006

The mechanisms‐based glycosidase inhibitor 2‐deoxy‐2‐[18F]‐fluoro‐β‐mannosyl [18F]‐fluoride was synthesized and its covalent binding to Agrobacterium β‐glucosidase was demonstrated in vitro.
Synthesis of carbon‐14 labelled xenalipin ‐ a potential hypolipidemic agent
Authors: Hill John A. , Eaddy John F.
Published: October 2006

Xenalipin 1 (4′‐trifluoromethyl‐2‐biphenylcarboxylic acid) was synthesized in the [14C]‐labelled form with specific activity 21.0 mCi/mmol suitable for metabolism and distribution studies in animals. The synthetic sequence involved conversion of [14C]‐ benzoic acid to the 4,4‐dimethyl‐2‐oxazoline derivative, formation of an organozinc compound, palladium‐catalyzed coupling of the arylzinc‐oxazoline with 4‐trifluoromethyliodobenzene, and acid hydrolysis. The radiochemical purity was 99.4%.
Preparation of mono‐15N‐cyanogen and mono‐13C‐cyanogen
Authors: Wilmes Rolf , Winnewisser Manfred
Published: October 2006

The preparation of the unsymmetrically isotope‐labelled title compounds was achieved in pure form for the first time. While mono‐15N‐cyanogen is available in a two‐step‐synthesis, the preparation of mono‐13C‐cyanogen requires five steps, the last step in both cases being the dehydration of mono‐15N‐e.g. mono‐13C‐oxamide with phosphorus pentoxide.
Synthesis of the rice herbicide HW‐52 [dichlorophenyl ring 14C(U)]
Authors: Kimura Ikuo , Yokoyama Norimasa , Kasahara Kaoru , Ueda Takao , Atsumi Kazunori , Filer Crist , Wright Christopher
Published: October 2006

14C‐Labeled 2′,3′‐dichloro‐4‐(ethoxymethoxy) benzanilide (HW‐52) (10) was synthesized in a total of 9 steps from 1, 3‐dinitrobenzene [14C(U)]. The key intermediate 2,3‐dichloroaniline [14C(U)] (7) was prepared from the starting material by a series of aromatic substitutions and functional group manipulations. Conversion to the final product was achieved in high yield by coupling and further functional group manipulations. The overall radiochemical yield was 1.88% and radiochemical purity of the product was greater than 98.8%.
The synthesis of N‐[4‐dimethylamino‐1‐butyl(1‐13C)‐N‐nitrosobenzamide], an inhibitor of tryspin; Cyanide does not exchange with acetonitrile
Authors: White Emil H. , Chen Yulong
Published: October 2006

The synthesis of N‐[4‐dimethylamino‐1‐butyl(1‐13C)‐N‐nitrosobenzamide], a powerful active‐site‐directed inhibitor of trypsin, is reported. An efficient use of 13C‐cyanide ion was achieved in the reaction with 1‐chloro‐3‐dimethylaminopropane, the first step of the synthesis. Acetonitrile was used as a co‐solvent with water in that step; no evidence was found for cyanide ion exchange with acetonitrile. The earlier report of such an exchange appears to be in error; the formation of hydrocyanic acid under the reaction conditions can account for the observations.
Synthesis of a radiotracer for studying dopamine uptake sites in vivo using PET: 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐[N‐11C‐methyl]tropane ([11C]CFT or [11C]WIN‐35,428)
Authors: Dannals Robert F. , Neumeyer John L. , Milius Richard A. , Ravert Hayden T. , Wilson Alan A. , Wagner Henry N.
Published: October 2006

2β‐Carbomethoxy‐3β‐(4‐fluorophenyl)‐[N‐11C‐methyl]tropane, a potent inhibitor of dopamine transport, was prepared by N‐methylation of the appropriate nor‐methyl precursor in DMF with [11C]iodomethane. After derivatization of unreacted precursor with a long chain acyl halide, the radiotracer was purified using reversed phase semipreparative HPLC. The average specific activity was 3065 mCi/μmole (calculated at the end‐of‐synthesis; EOS). The average time of synthesis including formulation was approximately 21 minutes.
Preparation of 15N‐13C‐fulminic acid
Authors: Wilmes Rolf , Winnewisser Manfred
Published: October 2006

The precursor for the title compound was prepared in a three‐step synthesis. The 13C‐label was incorporated in the first step employing 2‐13C‐ethyl acetate and the 15N‐label in the last step, using 15N‐sodium nitrite. Upon pyrolysis the precursor forms three fragments, one of them being the title compound.
Probing protein structure and dynamics by tritium NMR
Authors: O'Connell T. M. , Williams P. G. , Gerig J. T.
Published: October 2006

Tritium nmr spectroscopy of specifically tritiated tosylchymotrypsin has been used to examine the properties of the tosyl group in this protein. The unavoidable presence of several tritiated isotopomers complicates analysis of experiments and extensive computer simulations of relaxation behavior of tritiated species present were used in conjunction with models developed from crystallographic results to interpret the observations made. These analyses suggest that the tosyl group of tosylchymotrypsin at pH 4 is highly mobile in solution and occupies the lacation in the protein that is observed in the crystalline state only about 50% of the time.
The synthesis of carbon‐14 labeled pravastatin
Authors: Wallace M. A. , Dean D. C. , Ellsworth R. L. , Melillo D. G. , Marks T. , White R. F.
Published: October 2006

As asymmetric route to [14C]β‐hydroxycompactin 1 bearing the (S)‐2‐methyl‐[1‐14C]butanoate side chain has been developed. Methylation of [N‐[1‐14C]butyryl‐4‐(S)‐phenylmethyl‐2‐oxazolidinone 4 afforded a 95:5 mixture of diastereomeric [N‐(S,R)‐2‐methyl‐[1‐14C]butyryl]‐4‐(S)‐phenylmethyl‐2‐oxazolidinones 5,6 which were separated by preparative HPLC. Oxidative cleavage of 5 afforded optically pure (S)‐2‐methyl‐[1‐14C]butanoic acid. Acylation of alcohol 9 with optically pure (S)‐2‐methyl‐[1]14C]butyryl chloride afforded ester 10. Removal of the silyl either produced diastereomerically pure compactin 11. Hydroxylation was carried out by biotransformation with Mucor hiemelus to afford diastereomerically pure [[1‐14C]butanoate]β‐hydroxycompactin, [14C]Pravastatin 1.
Synthesis of [18F]‐(S)‐fluoxetine: A selective serotonine uptake inhibitor
Authors: Hammadi Akli , Crouzel Christian
Published: October 2006

The (S)‐N‐methyl‐γ‐[4‐(trifluoromethyl)phenoxy]benzenepropanamine, an antidepressant with potential applications in the treatment of other illnesses was labelled with fluorine‐18 for Positron Emission Tomography studies. The synthesis was accomplished from the [18F]‐4‐chlorobenzotrifluoride where [18F]‐(S)‐Fluoxetine was obtained with a radiochemical yield of 9–10% (decay corrected) and a specific radioactivity of 100–150 mCi/μmol (3.70–5.55 GBq/μmol) in a total synthesis time of 150 min. A facile isotopic exchange reaction was desmonstrated; it is expected to reduce the specific activity of the final [18F]‐product. The experimental parameters play an important role, which is discussed.
Facile synthesis of (4S)‐(−)‐[9‐3H]limonene
Authors: Hiraga Yoshikazu , Danjo Hiroshi , Ito Takatoshi , Suga Takayuki
Published: October 2006

(4S)‐[9‐3H]‐1‐Methyl‐4‐(1′‐methylethenyl)cyclohexene ((4S)‐(−)‐[9‐3H]limonene) was synthesized from (1′S,2RS)‐2‐(4′‐methylcyclohex‐3′‐enyl)porpanal ((4S,8RS)‐(−)‐1‐p‐menthen‐9‐al) via a convenient route in a high yield with improved enantiomeric purity.
14C‐labelling of NNC 756, a new dopamine D1 antagonist
Authors: Foged Christian , Hansen Louis B. , Halldin Christer
Published: October 2006

A 14C labelled form of (+)‐8‐chloro‐5‐(2,3‐dihydrobenzofuran‐7‐yl)‐7‐hydroxy‐3‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (NNC 756) (8) was synthesized in 7 steps, including resolvation of the active (+)‐form, starting from [14C]methyl iodide and 7‐benzofurancarbaldehyde. The overall radiochemical yield was 11%. The radiochemical purity of [4‐14C]NNC 756 was higher than 98% with a specific radioactivity of 24 mCi/mmol.
The synthesis of [14C]‐3S,4R‐4‐(4‐fluorophenyl)‐3‐(3,4‐methylenedioxyphenoxymethyl)piperidine hydrochloride (BRL 29060A), and mechanistic studies using carbon‐13 labelling
Authors: Willcocks K. , Barnes R. D. , Rustidge D. C. , Tidy D. J. D.
Published: October 2006

Paroxetine, BRL 29060A 1 has been labelled with both carbon‐14 and carbon‐13. Hydroxymethylation of 4‐(4‐fluorophenyl)‐1‐methyl‐1,2,5,6‐tetrahydropyridine, using [14C]formaldehyde, produced an enantiomeric mixture of products which was taken without separation through a multistage sequence. Resolution of the mixture of stereoisomers at the penultimate step gave [14C]BRL 29060A with the required configuration. The overall radiochemical yield was 8%. At some stage in this process, as shown by C‐13 labelling studies, scrambling of the label took place to give BRL 29060A with the majority of the label in the C‐2 position of the piperidine ring and the remainder at the expected 7‐methylene position. Further investigations of this route using carbon‐13 as the label are described. When sesamol, (3,4‐methylenedioxyphenol) was reacted with the O‐benzene sulphonate of (±)‐cis‐4‐(4‐fluorophenyl)‐3‐(hydroxy[13C]methyl)‐l‐methylpiperidine, an inversion of configuration resulted via the previously described 1‐aza[3.1.1]bicycloheptane ring system. It is also shown that the corresponding (±)‐trans‐substituted piperidine, under similar conditions, does not undergo this inversion.
A method for synthesis of 14C‐labelled styrene
Authors: Majcherczyk Andrzej , Braun‐Lüllemann Annette , Hüttermann Aloys
Published: October 2006

Side‐chain and ring 14C‐labelled styrene were synthesised from labelled benzene and acetaldehyde via bromobenzene, Grignard‐reagent and 1‐phenylethanol. Uniformly 14C‐labelled styrene can be also prepared using this method. By‐products were identified and the purity of products was determed by GC‐MS.
Synthesis of (2,3‐13C2) erucic acid
Authors: Olsen Julie A. , Bukata Pablo A.
Published: October 2006

The synthesis of (2,3‐13C2) erucic acid, for use in metabolic studies, is reported. The synthesis employs a repeated 3 step reaction sequence using 13C labeled triethylphosphonoacetate to extend C18:1, oleyl alcohol, by 4 carbons. The starting alcohol is first oxidized with PCC and the resulting aldehyde is condensed with triethyl(1‐13C)phosphonoacetate. The product, an α,β unsaturated ester, is reduced with (Ph3PCuH)6 to ethyl eicosenoate. Reduction with LAH gives eicosenoyl alcohol. A repetition of the reaction sequence using triethyl(2‐13C) phosphonoacetate results in ethyl(2,3‐13C2)erucate. The (2,3‐13C2) erucic acid, obtained by hydrolysis with alcoholic KOH, gave 13C NMR signals of δ 24.6 and 34.1 ppm for C‐3 and C‐2 respectively with a J=34.9 Hz. The overall yield was 5.5%.
The synthesis of 4‐2H‐α‐farnesene and 1‐2H‐α‐farnesene
Authors: Fielder Simon , Rowan Daryl D. , Reay Peter F.
Published: October 2006

α‐Farnesene deuterated at C1 or C4 was synthesised by regiospecific deuteration of 2‐geranyl‐3‐methylsulpholene (2). Treatment of (2) with butyl lithium in dimethylpropenylurea (DMPU) mediated THF resulted in deprotonation at C2. Quenching with D2O/CH3CO2D gave a mixture of deuterated sulpholenes (43‐68%), predominantly 2‐2H‐2‐geranyl‐3‐methylsulpholene (5), together with bond migrated product (25‐49%). Thermal elimination of sulphur dioxide gave 4‐2H‐α‐farnesene (6)(85%) but with low deuterium incorporation (60%) and poor regiospecificity. Treatment of (2) with butyl lithium in TMEDA mediated THF resulted in deprotonation at C5 with minimal bond migration (1%). Quenching with D2O/CH3CO2D yielded 5‐2H‐2‐geranyl‐3‐methylsulpholene (18)(75%) which on thermolysis gave 1‐2H‐α‐farnesene (19)(86%) with high regiospecificity and improved deuteration (85%). Some mechanistic aspects of the alkylation of 3‐methylsulpholenes are discussed.
Synthesis of [1‐14C]‐2,2‐difluoroethene from [14C]‐formaldehyde
Authors: Ruzicka Jan A. , Qiu Weiming , Baker Max T. , Burton Donald J.
Published: October 2006

[1‐14C]‐2,2‐Difluoroethene was synthesized from [14C]‐formaldehyde using a modification of the Wadsworth‐Emmons reaction, via formation of the intermediate (EtO)2P(O)CF214CH2OSiMe3. This highly volatile product was collected in a liquid nitrogen trap at a purity of >97% and specific activity of 0.2 mCi/mmol, with yields of 10 ‐ 15%.
A new synthesis of double labeled [7, 9 ‐13C2] folic acid
Authors: Cowart Marlon , Falzone Christopher J. , Benkovic Stephen J.
Published: October 2006

A convenient small scale chemical synthesis of double labeled folic acid with 13C at positions C‐7 and C‐9 is reported. [1,3‐13C2] acetone was converted into folic acid in two steps, with [1, 1, 3]‐trichloroacetone as the labeled intermediate.
A practical approach to the synthesis of 14C‐labeled amino acid and simple peptide
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

A convenient method for the synthesis of phenylmethyl N‐methyl (carboxy‐14C) glycine hydrochloride (Z) is described. It involves the carboxylation of transmetalated organostannane compound 4 which itself is accessible by established procedure. Success in preparing the labelled amino acid Z enabled us to synthesize target N‐glycyl‐N‐methyl(carboxy‐14C) glycine (10) by conventional coupling protocol.
The synthesis of [14C]SK&F 97426A. A novel bile acid sequestrant
Authors: Lawrie Kenneth W M , Aggarawal Pravina , Saunders David
Published: October 2006

SK&F 97426A (10), a 1% crosslinked 11‐trimethylammonioundecylmethacrylate chloride ethylene glycol dimethacrylate co‐polymer bile acid sequestrant, has been prepared in two carbon‐14 labelled forms, namely in the 1‐position of the undecyl side chain and the pendant N‐methyl group. 11‐Bromo[1‐14C]undecyl methacrylate has been prepared and conditions developed for its small scale suspension polymerisation.
Synthesis of 14C‐labeled copolymers for drug delivery studies
Authors: Rhee Sung W. , Reist Elmer J. , Rock Marie T.
Published: October 2006

14C‐labeled polyanhydride copolymers [(20:80/1,3‐bis)(p‐carboxyphenoxy)‐propane(CPP):sebacic acid (SA)] (7 and 13) were synthesized according to schemes I and II: 14C‐labeled sebacic acid (2,9‐14C2) (5) and 14C‐labeled CPP 1,3‐bis(p‐carboxyphenoxy)‐propane (labeled at C‐1, C‐3 of the propyl group) (11) were transformed to the corresponding mixed anhydrides (6 and 12) as prepolymers respectively by reaction with acetic anhydride. The labeled mixed anhydride prepolymers (6 and 12) were condensed with unlabeled counter‐prepolymers (12′ and 6′) to give the labeled polyanhydride copolymers (7 and 13). The labeled copolymers (7 and 13) were identified and characterized by gel permeation chromatography (GPC).
Model reactions targeted at the synthesis of carbon‐14 labeled CI‐996, a potent antagonist of angiotensin II receptor (1)
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

A reaction sequence suitable for the preparation of an analog of 2‐propyl‐1‐[2′‐(1H‐tetrazol‐5‐yl)[1,1′‐biphenyl]‐4‐yl]methyl‐4‐[2‐(trifluoroacetyl)‐1H‐pyrrol‐1‐yl]‐1H‐imidazole‐5‐carboxylic acid, with 14C at the methylene bridge was developed. The would‐be labeled fragment (12) was derived from 4‐iodobenzenemethanol (6), which itself was constructed from 1,4‐dibromobenzene by the application of silicon chemistry. Pd° catalyzed coupling of TBDMS protected 6 and a tetrazole borate 10 gave the compound 12 which upon further transformation to the mesylate 13, N‐alkylated an imidazole to furnish target compound.
Synthesis of methyl [5,6,8,9,14,‐3 H6]‐hepoxilin B3 and its conversion into methyl [5,6,8,9,14,15‐3H6]‐hepoxilin A3
Authors: Demin P. M. , Pivnitsky K. K. , Vasiljeva L. L. , Pace‐Asciak C. R.
Published: October 2006

The selective tritiation of methyl 10(R/S)‐hydroxy‐11(R),12(S)‐epoxyeicosa‐5,8,14‐triynoate into two C10‐epimeric [3H6]‐hepoxilins B3 methyl esters is described. These compounds are subsequently converted into two C8‐epimeric [3H6]‐hepoxilins A3 methyl esters by allylic rearrangement under Mitsunobu conditions via corresponding benzoates.
Synthesis of 14C‐labelled bromocresol green and metacresol purple
Authors: Thourel P. , Vandais A. , Noel J‐P. , Beaucourt J‐P.
Published: October 2006

[methyl‐14C]‐Bromocresol green 1 was synthesized from [14C] ‐ methyl iodide in four steps via 3‐[methyl‐14C]‐methylanisole 3, [methyl‐14C]‐metacresol 4 and [methyl‐14C]‐metacresol purple 6. The overall yield of 1 from [14C] methyl iodide was 5.3% and the specific activity 112 mCi/mmol.
Synthesis of 4‐stannylated tamoxifen analogues; useful precursors to radiolabelled idoxifene and aziridinyl 4‐iodotamoxifen
Authors: McCague Raymond , Potter Gerard A.
Published: October 2006

The 4‐stannylated tamoxifen analogues (E)‐1‐[4‐[2‐(N‐pyrrolidino)ethoxy]phenyl]‐1‐[4‐(tributylstannyl)phenyl]‐2‐phenyl‐1‐butene and (E)1‐[4‐[2‐(aziridin‐1‐yl)ethoxy]phenyI]‐1‐[4‐(tributylstannyl)phenyl]‐2‐phenyl‐1‐butene have been synthesised as precursors to radiolabelled idoxifene, an important new drug for the treatment of breast cancer, and to aziridinyl 4‐iodotamoxifen, a potentially useful biological research tool for studying the action of tamoxifen, respectively.
Metallation/reduction as a new approach to tritium labeling. The synthesis of [3H]ibogaine
Authors: Seltzman Herbert H. , Odear Denise F. , Laudeman Christopher P. , Carroll F. Ivy , Wyrick Christopher D.
Published: October 2006

A new method is presented for the tritiation of aryl compounds with tritium gas which is conducted on the underivatized substrate. Combined directed ortho metallation and facile reduction of the carbonpotassium bond affords incorporation of tritium at high specific activity under mild conditions. The metallation/reduction method is demonstrated for the preparation of [3H]ibogaine.
Difunctional two‐carbon molecules derived from [11C]cyanide
Authors: Thorell Jan‐Olov , Stone‐Elander Sharon , Elander Nils
Published: October 2006

A synthetic strategy for producing new difunctional molecules for potential use as radiolabelling precursors derived from [11C]cyanide is presented. No‐carrier‐added [11C]CN− was reacted with chloromethyl pivalate to generate the nitrile [11C]cyanomethyl pivalate, which was subsequently converted to ethyl 1 [1‐11C]glycolate, 2, with acid and alcohol, or to [1‐11C]glycolic acid, 4, using aqueous acid. [1‐11C]Ethylene glycol, 3, and [2‐11C]2‐aminoethanol 5, were obtained by reduction of2 and 1, respectively, with lithium aluminum hydride. Conditions for obtaining conversions ca. 90% are described. By using a microwave wave‐guide cavity to speed up transformations requiring elevated temperatures, all five carbon‐11 labelled compounds were synthesized in less than a total of 3 min.
Radiosynthesis of (±)‐1‐(2‐bromo‐4,5‐dimethoxybenzyl)‐7‐hydroxy‐6‐methoxy‐2‐[11C]‐methyI‐l,2,3,4‐tetrahydro‐isoquinoline, [11C]A‐69024: A non‐benzazepine antagonist for studying dopamine D1 receptors In vivo using PET
Authors: Kassiou Michael , Mathews William B. , Musachio John L. , Ravert Hayden T. , Lambrecht Richard M. , Dannals Robert F.
Published: October 2006

(±)‐1‐(2‐bromo‐4,5‐dimethoxybenzyl)‐7‐hydroxy‐6‐methoxy‐2‐[11C]‐methyl‐1,2,3,4‐tetrahydroisoquinoline, (HCJA‐69024, a selective ligand for the D1 receptor was prepared by N‐alkylation of (±)N‐desmethyl A‐69024 with [11C]methyl iodide in DMF. The radiotracer was purified by semi‐preparative reverse‐phase HPLC. The average specific activity was 1950 mCi/μmol calculated at end‐of‐synthesis (EOS). The average time of synthesis including formulation was 20 minutes.
Radiolabeling kit/generator for 5‐radiohalogenated uridines
Authors: Baranowska‐Kortylewicz Janina , Helseth Lynn D. , Lai Jing , Schneiderman Martin H. , Schneiderman G. Sue , Dalrymple Glenn V.
Published: October 2006

A rapid, simple and inexpensive synthesis of 5‐radiohalogenated‐2′‐deoxyuridine from 5‐trimethylstannyl‐2′‐deoxyuridine is described. The total reaction and purification time including thin layer chromatography (tlc) for quality control is less than 30 min. This method produces excellent yields (>95%) of 123I‐, 125I‐, 131I‐UdR. The radiochemical purity of all tested preparations (>20) was determined to be greater than 99%. This new method is the basis of a radiolabeling kit/generator for preparation of radiohalogenated nucleosides. 2′‐Deoxyuridine (UdR) halogenated with a stable isotope of bromine was also synthesized indicating that the method can be applied to the preparation of 5‐radiobromo‐2′‐deoxyuridine (BUdR).
[11C]cyanogen bromide in the synthesis of 1,3‐di(2‐tolyl)‐[11C]guanidine
Authors: Westerberg Göran , Kärger Wiebke , Onoe Hirotaka , Långström Bengt
Published: October 2006

The title compound was 11C‐labelled in a one‐pot procedure using [11C]cyanogen bromide as the key intermediate. Synthesis time was 31–33 min counted from the end of bombardment, affording 1,3‐di(2‐tolyl)‐[11C]guanidine (6) in 87 % decay‐corrected radiochemical yield counted from [11C]cyanogen bromide. The specific radioactivity of the product at the end of synthesis was 118 GBq μmol−1 (3.2 Ci μmol−1). Autoradiographic studies on slide‐mounted rat brain sections showed specific binding of guanidine (6), but when injected intravenously into Rhesus monkey, brain uptake was very low, indicating that the 1,3‐di(2‐tolyl)‐[11C]guanidine did not cross the blood‐brain barrier.
Synthesis of (1, 2‐13C2) 2‐phosphoglycolic acid
Authors: O'Connor Edward J. , Tomita York , McDermott Ann E.
Published: October 2006

The synthesis of (1,2‐ 13C2) 2‐phosphoglycelic acid, 5, from commercially‐available (1,2‐ 13C2) bromoacetic acid is described along with some of its solution NMR characteristics.
Efficient routes to isotopically labelled epichlorohydrins ((chloromethyl) oxiranes)
Authors: O'Hagan David , White Jeffrey , Jones David A.
Published: October 2006

Efficient routes are developed for the synthesis of variously labelled 2H‐ and 13C‐ labelled epichlorohydrins prepared from appropriately labelled acetic acids and sodium borodeuteride. The route is versatile and can be used for strategic location of isotopes at C‐1, C‐2 and C‐3 of epichlorohydrin. By way of demonstration [2‐13C]‐, [2‐2H]‐, [3‐2H2] and [2‐2H, 3‐2H2]‐ epichlorohydrins have been prepared. In addition the syntheses can be adapted for the preparation of enantiomerically pure and isotopically labelled epichlorohydrins.
Synthesis of 123I‐and labelled 5‐iodo‐6‐nitroquipazine
Authors: Mathis Chester A. , Enas Joel D. , Hanrahan Stephen M. , Akgün Eyup
Published: October 2006

The syntheses of the potent and selective serotonin reuptake complex radioligands [123I]‐ and [125I]5‐iodo‐6‐nitroquipazine (5‐iodo‐6‐nitro‐2‐piperazinylquinoline) are reported. A seven step synthetic sequence provided the BOC‐protected 5‐tributyltin‐6‐nitroquipazine precursor for radioiodination. End of synthesis radioiodination yields of ∼40% for 123I and ∼60% for 125I were achieved resulting in labelled products with high specific activities (>4000 and >2000 Ci/mmol, respectively) and radiochemical purities (>98%).
Synthesis of [2‐14C] fantofarone or 1‐[4‐[3‐N‐methyl N‐[3,4‐dimethyl β‐phenethyl] amino propyloxy] benzene sulfonyl]‐2‐isopropyl [2‐14C] indolizine
Authors: Pointeau P. , Berger Y.
Published: October 2006

Sodium [1‐14C] isobutyrate: 1 was obtained by carbonation of isopropyl magnesium bromide with 14CO2. From: 1 [1‐14C] isobutyryl chloride: 3 was prepared, which through the successive actions of diazomethane and hydrogen bromide gave rise to 1‐bromo 3 methyl [2‐14C] 2‐butanone: 5.

The latter lead to the indolizine: 6 which by a route patterned after that used to make unlabelled Fantofarone gave the [2‐14C‐indolizyl] Fantofarone: 8 (specific radioactivity: 58.2 mCi/mMole) overall yield 9.9% based on [14C] BaCO3.
One‐step preparation of [2,3‐3H]1‐aminocyclopropanecarboxylic acid: A useful ligand for strychnine‐insensitive glycine receptors
Authors: Lewin A. H. , Lamb P. B. , Popik P. , Skolnick P.
Published: October 2006

Catalytic hydrogenation of 1‐aminocyclopropenecarboxylic acid under tritium gas afforded [2,3‐3H]1‐aminocyclopropanecarboxylic acid with specific activity 26 Ci/mmol, determined by a combination of 1H and 3H NMR. Pilot radioligand binding assays indicate this compound will be a useful probe for the NMDA receptor‐associated strychnine‐insensitive glycine receptor.
Synthesis of [14C]E1077, a novel parenteral cephalosporin antibiotic
Authors: Kai Yasunobu , Chiku Shigeru
Published: October 2006

(−)‐(RS)‐(E)‐3‐[(6R,7R)‐7‐((Z)‐2‐(5‐amino‐1,2,4‐thiadiazol‐3‐yl)‐2‐fluoromethoxyiminoacetamide]‐2‐carboxy‐8‐oxo‐5‐thia‐1‐azabicyclo[4.2.0]oct‐2‐ene‐3‐yl[‐2‐propenyl](carbamoylmethyl) ethylmethylammonium hydroxide inner salt (E1077), a new parenteral cephalosporin with well‐balanced antibacterial spectrum and potent antibacterial activity, was labelled with carbon‐14, starting from potassium [14C]thiocyanate which on reaction with (Z)‐2‐(N‐chloroamidino)‐2‐fluoromethoxyiminoacetic acid (I) gave(Z)‐2‐(5‐amino‐1,2,4‐[5‐14C]thiadiazol‐3‐yl)‐2‐fluoromethoxyiminoacetic acid (II).

(RS)‐[(E)‐3‐](6R,7R)‐7‐Amino‐2‐carboxy‐8‐oxo‐5‐thia‐1‐azabicyclo[4.2.0]oct‐2‐ene‐3‐yl[‐2‐propenyl](carbamoylmethyl) ethylmethylammonium hydroxide inner salt (III) was acylated with the above acid using the POCl3‐DMF method, to afford the title compound (IV); [14C]E1077, having a specific activity of 3.36 MBq/mg, was obtained in 50.3% overall radiochemical yield, with a radiochemical purity of more than 97.1%.
Synthesis of (R)‐(+)‐1,2,3,6‐tetrahydro‐4‐[U‐14C]phenyl‐1‐ [(3‐phenyl‐3‐cyclohexenyl‐1‐yl)methyl]pyridine, a potential antipsychotic agent
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

1,2,3,6‐Tetrahydro‐4‐[U‐14C]phenylpyridine (12) was synthesized and coupled to (R)‐3‐phenyl‐3‐cyclohexene‐1‐carboxylic acid to make the titled compound 7 in 21% overall yield. Purification considerations were an important factor in the choice of a reaction sequence to 7, and successful synthesis was facilitated by the superiority of BF3.OEt2 as dehydrating reagent in this system. This otherwise problematic sequence offers an efficient and simple route to compound 7 (PD 143188).
An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C‐14 labeled isotopomers
Authors: Wheeler William J. , Kuo Fengjiun
Published: October 2006

Two 14C‐isotopomers of duloxetine HCl (S‐(+)‐N‐methyl‐3(1‐naphthal‐ enyloxy)‐3(2‐thiophene)propanamine hydrochloride), a potent mixed serotonin/norepinephrine uptake inhibitor have been prepared by an asymmetric synthesis. The palladium catalyzed cross‐coupling of 2‐thienoyl chloride (3c) (or its [carbonyl‐14C] isotopomer 3d) with vinyl tri‐n‐butylstannane, followed by addition of HCl afforded the key pro‐chiral intermediate chloroketone (5a, b). Chiral reduction with borane in the presence of the appropriate oxazaborolidine catalyst (14a or b) provided the S‐chloroalcohol (7a) and its 14C‐labeled counterpart 7b or the analogous R‐chloroalcohol (6). Activation of 7a, b by reaction with NaI/ acetone, followed by reaction of the corresponding iodoalcohol with methylamine yielded the penultimate aminoalcohols (8a, b). Formation of the alkoxide with NaH, followed by reaction with 1‐fluoronaphthalene yielded duloxetine or its 14C‐labeled isotopomer 9. Alternatively, reaction of 6 with 1‐naphthol‐[1‐14C] under Mitsunobu conditions afforded arylether 10a, b, which was in turn activated by reaction with NaI/acetone. Subsequent reaction of 10c, d with methylamine followed by salt formation yielded duloxetine or its naphthalene‐labeled isotopomer (13) as their HCl salts.
Site‐specific labelling of caged atp with deuterium or 18oxygen
Authors: Corrie John E. T. , Reid Gordon P.
Published: October 2006

[3‐D]2‐Nitroacetophenone and [alcohol‐18O]‐1‐(2‐nitrophenyl)ethyl alcohol were prepared and used to synthesise labelled P3‐l‐(2‐nitrophenyl)ethyl esters of ATP (“caged ATP”) with isotope present either as deuterium on the 3‐position of the nitrosubstituted ring or as 18oxygen in the bridging position between the terminal phosphate and the nitrophenylethyl group. The availability of the deuterated compounds enabled complete assignment of their 1H NMR spectra.
Preparation of 1‐methyl‐4‐[4‐(7‐chloro‐4‐quinolyl‐[3‐14C]‐amino)benzoyl]piperazine
Authors: Wang Theodore S. T. , Fawwaz Rashid A. , Van Heertum Ronald L.
Published: October 2006

1‐Methyl‐4‐[4‐(7‐chloro‐4‐quninolyl‐[3‐14C]amino)‐benzoyl]piperazine (V) was prepared for pharmacokinetic and pharmacodynamic evaluation. The synthesis of V was accomplished first by a modified Claisen ester condensation reaction of diethyl‐[2‐14C]‐malonate, triethyl orthoformate, and acetic anhydride in the presence of ZnCl2 to form ethyl ethoxymethylene‐[2‐14C]‐malonate (I), which was further condensed with m‐chloroaniline to yield 7‐chloro‐4‐hydroxy‐3‐[14C]‐quinoline‐ethylcarboxylate (II). Saponification of II yielded the corresponding carboxylic acid (III). Decarboxylation of the acid group upon heating and a substitution of the 4‐OH group of compound III into chlorine atom with POCl3 produced 4,7‐dichloro‐[3‐14C]‐quinoline (IV), which then was reacted with 1‐methyl‐4‐(pamino‐benzoyl)piperazine to form the title compound V. There were a total of five steps of reaction, with a overall yield of 34.3%. The specific activity was 1.74 mCi/mmol.
Synthesis of 1,2,3‐trideutero amines, alcohols and hydrocarbons from tricarbonyliron(0) complexes of 1‐heterodienes and homodiens
Authors: Danks Timothy N.
Published: October 2006

A simple procedure for the synthesis of 1,2,3‐trideutero amines, alcohols and hydrocarbons from the reaction between lithium aluminiumdeuteride and tricarbonyliron(0) complexes of 1‐heterodienes and homo‐dienes is reported.
No‐carrier‐added (NCA) synthesis of 6‐[18F]fluoro‐L‐DOPA using 3,5,6,7,8,8a‐hexahydro‐7,7,8a‐trimethyl‐[6s‐(6α,8α,8αβ)]‐6,8‐methano‐2H‐1,4‐benzoxazin‐2‐one
Authors: Horti Andrew , Redmond D. Eugene , Soufer Robert
Published: October 2006

3,5,6,7,8,8a‐Hexahydro‐7,7,8a‐trimethyl‐[6S‐(6α,8α,8αβ)]‐6,8‐methano‐2H‐1,4‐benzoxazino‐2‐one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6‐[18F]Fluoro‐L‐DOPA. Direct condensation of 3,4‐dimethoxy‐2‐[18F]fluorobenzaldehyde (1a) or 6‐[18F]fluoropiperonal (1b) in the presence of NaH with 2 gave the corresponding [18F]‐3‐[(2‐fluorophenyl)methylene]‐3,5,6,7,8,8a‐hexahydro‐7,7,8a‐trimethyl‐[6S‐(3Z,3α,6α,8α,8αβ)]‐6,8‐methano‐2H‐1,4‐benzoxazin‐2‐one derivative 3a or 3b as a single stereoisomer. L‐Selectride® promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [18F]‐3‐[(2‐fluorophenyl)methyl]‐3,5,6,7,8,8a‐hexahydro‐7,7,8a‐trimethyl‐[3S‐(3α,6α,8α,8αβ)]‐6,8‐methano‐2H‐ 1,4‐benzoxazin‐2‐one derivatives (4a, b) without affecting the orientation of diastereofacial discrimination. Deprotection of the derivatives 4a,b yielded 6‐[18F]fluoro‐L‐DOPA (e.e. > 90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity > 2000 mCi/μmol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6‐[18F]fluoro‐D,L‐DOPA (10–12% radiochemical yield) and, after chiral separation, 6‐[18F]fluoro‐L‐DOPA (e.e. 98%, 4–5% radiochemical yield). A “cold” enantioselective synthesis of 6‐fluoro‐L‐DOPA has been effected with total chemical yield 15% (e.e. 93.4%).
Synthesis of [8‐14C]‐2,6‐dichloro‐9H‐purine, a radiolabelled precursor for 14C‐nucleosides
Authors: Valsborg Jacob S. , Knutsen Lars J. S. , Lundt Inge , Foged Christian
Published: October 2006

The synthesis of [8‐14C]‐2,6‐dichloro‐9H‐purine (2), a radiolabelled precursor for preparing 14C‐labelled nucleosides, is described. Triethyl[14C]orthoformate was reacted with 4,5‐diamino‐2,6‐dichloropyrimidine (1) in acetonitrile at 90°C with methanesulfonic acid as catalyst to generate 2 in 84% radiochemical yield. Reaction of 2 with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose produced [8‐14C]‐9‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)‐2,6‐dichloropurine (3) in 86% yield. The radiochemical purity of 3 was higher than 98% with a specific activity of 36 mCi/mmol. This method has general application to 14C‐labelling of purines in drug development.
An efficient synthesis of 1‐[13C]‐bromobenze
Authors: Geletneky Christian , Balzer Hartmut , Bock Willi , Berger Stefan
Published: October 2006

Various routes to functionalized benzenes labelled in position 1 were compared. 1‐[13C]‐Bromobenzene has been synthesized in 7 steps with an overall yield of 5.4% from [13C]‐BaCO3, by optimizing the direct transformation of p‐nitrophenol into bromobenzene.
Preparation and investigation of [14C]padimate‐O and [14C]N‐nitroso‐N‐nor‐padimate‐O
Authors: Lewin Anita H. , Fudala Louise
Published: October 2006

Carbonation of the aryl lithium obtained from p‐N,N(dimethylamino)bromobenzene with carbon‐14 labeled carbon dioxide, followed by esterification gave [CO2‐14C]p‐N,N(dimethylamino)benzoate 2‐ethylhexyl ester (Padimate‐O). This material underwent slow decomposition to [14C]N‐nor‐Padimate‐O and [14C]N‐formyl‐N‐nor‐Padimate‐O. Nitrosation of [14C]Padimate‐O with sodium nitrite afforded [14C]N‐nitroso‐N‐nor‐Padimate‐O.
Synthesis of tritium‐labelled 5‐chloro‐2′,3′‐dideoxy‐3′‐fluorouridine (935u83) ‐ a selective anti‐HIV agent
Authors: Hill John A. , Bankston Donald D.
Published: October 2006

[5′‐3H]‐5‐Chloro‐2′,3′‐diodeoxy‐3′‐fluorouridine (1; R = [3H]) was prepared at a specific activity of 10.2 Ci/mmol suitable for development of a radioimmunoassay procedure. The synthetic sequence employed controlled oxidation of unlabelled 1 to the 5′‐aldehyde (2), isolation as the imidazolidine adduct (3), regeneration of the free aldehyde, reduction with [3H]NaBH4, and purification by preparative TLC. The radiochemical purity was 98.0%.
Carbon‐11 labeling of a potent, nonpeptide, at1‐selective angiotensin‐II receptor antagonist: MK‐996
Authors: Mathews William B. , Burns H. Donald , Dannals Robert F. , Ravert Hayden T. , Naylor Elizabeth M.
Published: October 2006

[α‐11C]Benzoyl chloride was synthesized and purified by normal phase HPLC. [11C]MK‐996 ([11C]N‐[[4′[(2‐ethyl‐5,7‐dimethyl‐3H‐imidazo [4,5‐b]pyridin‐3‐yl)methyl][1,1′‐biphenyl]‐2‐yl]sulfonyl]‐benzamide), a potent and selective ligand for the AT1 receptor, was prepared by N‐benzoylation of L‐159,221 with [α‐11C]benzoyl chloride in tetrahydrofuran using lithium bis(trimethylsilyl)amide as a base. The radiotracer was purified by semi‐preparative reverse‐phase HPLC. The average specific activity was 1162 mCi/μmol calculated at end‐of‐synthesis (EOS). The average time of synthesis including formulation was 30 minutes.
Hemisynthesis of [3′‐14C]‐Taxotere®
Authors: de Suzzoni S. , Boullais C. , Vandais A. , Noel J. P.
Published: October 2006

A new route to semisynthetic Taxotère®, 1. is described using the mixed anhydride obtained from 2,4,6‐trichlorobenzoyl chloride and [3‐14C]‐cinnamic acid 6, for the esterification of 7,10‐O‐diTroc‐10‐deacetylbaccatin III, 4. Hydroxyamination on the unsatured C‐2′,3′,deprotection of the C‐7,10‐Troc groups of the ester 7 gave Taxotère® 1. [3′‐14C]Taxotère® 9 (specific activity: 50 mCi/mmol) was obtained from [3‐14C]‐cinnamic acid 5 with a 5% yield.
Synthesis and purification of 13C labelled xanthine derivatives
Authors: Boukraa M. S. , Deruaz D. , Bannier A. , Desage M. , Brazier J. L.
Published: October 2006

3‐[Methyl‐13C]xanthine, 7‐[Methyl‐13C]xanthe, 1,3‐[Dimethyl‐13C2]xanthine (theophylline‐1,3‐[13CH3]2), 1,7‐[Dimethyl‐13C2]xanthine (paraxanthine‐1,7‐[13CH3]2), and 3,7‐[Dimethyl‐13C2]xanthine (theobromine‐3,7‐[13CH3]2) were synthesized by nucleophilic substitution reaction (SN2) from xanthine (X) and iodomethane‐[13C]. The 3‐isobutylparaxanthine‐7‐[13CH3] was prepared from 3‐isobutyl‐1‐methylxanthine (IBMX). The compounds were purified by reverse phase semipreparative liquid chromatography and their chemical structure and purity verified by GC‐MS.
Synthesis of non ‐ carrier added [N ‐ methyl ‐ 11C] roxithromycine
Authors: Barre L. , Lasne M. C. , Charbonneau P.
Published: October 2006

Roxithromycine, a new macrolide, was labelled with [11C]CH3I in a good radiochemical yield (40‐45%)and high specific activities (500‐550mCi/μmol). This antibiotic may be useful for detecting pulmonar or cerebral infection foci using positron emission tomography.
Preparation of riboflavin specifically labeled in the 5′‐hydroxymethyl terminus using a vitamin B2‐aldehyde‐forming enzyme from Schizophyllum commune
Authors: Kekelidze Tea N. , Edmondson Dale E. , McCormick Donald B.
Published: October 2006

A method is described for synthesis of riboflavin selectively labeled in the hydrogens at the 5′‐hydroxymethyl position. In this method, a vitamin B2‐aldehyde‐forming enzyme from Schizophyllum commune is used to specifically and completely oxidize the 5′‐hydroxymethyl of riboflavin to the 5′‐aldehyde. This reaction is monitored spectrophotometrically by the reduction of 2,6‐dichlorophenolindophenol at 600 nm. Appearance of aldehyde product was directly quantitated by reverse‐phase high‐performance liquid chromatography. Product is extracted from the incubation mixture by phenol after saturation with (NH4)2SO4 and then further purified by benzyl alcohol extraction. The 5′‐aldehyde is reduced with appropriately labeled sodium borohydride to yield the vitamin specifically labeled in the 5′‐hydroxymethyl group.
Synthesis of isotopically labelled pyridoindolone 5‐HT3 receptor antagonists (1)
Authors: Prakash Shimoga R , Cable Karl M , Correa Itzela D , Fellows Lan , Montgomery Stephen , Newman John J , Waterhouse Lan , Wells Guy N , Sutherland Derek R
Published: October 2006

Syntheses of labelled versions of 5‐HT3 receptor antagonists, Alosetron and Lurosetron, are described. [14C]Alosetron was prepared by routes utilizing either Fischer indolisation of an amidohydrazine or palladium‐mediated cyclisation of an aryl enaminone as key steps. 2H and 13C versions of Alosetron were prepared from suitably labelled imidazoles. Lurosetron was labelled in either the methylene bridge carbon or carbonyl carbon, using 14C‐labelled paraformaldehyde or phosgene, respectively.
Very high isotope incorporation in the C‐1 position of glucose by exchange with deuterium or tritium gas
Authors: Long Mervyn A. , Morimoto Hiromi , Williams Philip G.
Published: October 2006

The experimental conditions which control the exchange from deuterium or tritium gas into the C‐1 proton position of glucose in aqueous solution have been studied in detail, with a view to determining the factors which maximize exchange into glucose, but minimize exchange into the solvent water. The favoured conditions for producing glucose with close to 100% isotope labelling in the C‐1 position, and with negligible formation of labelled byproducts, were a reaction time of 6 to 8 hours, a temperature of 60 °C, and a pH of 7 or higher. Pd/BaSO4 was the preferred catalyst and slow pre‐addition of the deuterium or tritium gas to the catalyst bed was essential to maximize the subsequent isotope exchange into the substrate.
Synthesis of disodium [benzene‐U‐14C]‐(4‐chlorophenylthio)methylenediphosphonate, [benzene‐U‐14C]‐tiludronate
Authors: Burgos Alain , Ellames George J.
Published: October 2006

Disodium [benzene‐U‐14C]‐(4‐chlorophenylthio)methylenediphosphonate, [benzene‐14C]‐Tiludronate, 2, has been prepared in six steps from [benzene‐U‐14C]‐acetanilide in an overall radiochemical yield of 41%. A key step in this transformation was the efficient conversion of [U‐14C]‐4‐chloroaniline to [benzene‐U‐14C]‐4‐chlorophenylthiocyanate, 5, in 83% yield by treatment of the corresponding diazonium salt, 9, with iron (III) thiocyanate. It should be noted that formation of the isomeric [benzene‐U‐14C]‐4‐chlorophenylisothiocyanate, 11, as a byproduct, was observed in only ∼ 1% yield.
Preparation Microbiologique Du 2‐CETO‐3‐Desoxy‐D‐Gluconate 1‐14C ou U‐14C
Authors: Pouyssegur J.
Published: October 2006

A E. Coli K 12 mutant having lost 2‐keto‐3‐desoxy‐gluconate kinase activity is unable to utilize glucuronate as a unique carbon source. However, this strain is able to partially convert glucuronate into KDG in resting cells conditions reported here.

A method is described making it possible to produce 1‐14C‐KDG or U‐14C‐KDG when the kinase cells metabolise 6‐14C or U‐14C‐D‐glucuronate. The radioactive KDG accumulated in the incubation medium has been purified thanks to a biological specific method followed by chromatography on anionic resin. The yield of the purified KDG from the hexuronate is about 20%. According to chromatographic criteria and specific conversion by KDG‐kinase, the product obtained has been authenticated as true KDG.
The synthesis of 14C‐eugenol and isoeugenol labeled in the methoxy position
Authors: Rabinowitz J. L. , Weinberg J. E. , Gennaro A. R. , Zanger M.
Published: October 2006

Methylation under pressure of o‐allyloxyphenol with 14C‐metheyl iodide was successfully used for the synthesis of 14C‐eugenol and isoeugenol labeled in the methoxy position. Eugenol and isoeugenol are important compounds in the practice of dentistry.
Synthesis of 2‐pyrrolidinone‐5‐14C
Authors: Villani A. J. , Mendelson W. L. , Blackburn D. W.
Published: October 2006

A convenient synthesis of the pharmacological intermediate 2‐pyrrolidione‐5‐14C, was developed using potassium cyanide 14C as starting material. Potassim cyanide‐14C was converted to 2‐pyrrolidinone‐5‐14C in an overall 56% radiochemical yield.
Synthesis of labeled anti‐inflammatory agents
Authors: Hafferl W. , Hary A.
Published: October 2006

The synthesis of the anti‐ inflammatory agents d‐2‐(6′‐methoxy‐2′‐naphthyl)‐propionic acid and 1‐2‐(6′‐methoxy‐2′‐naphthyl)‐propanol labeled with 14C and 3H is described.