bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 123I‐ and 131I‐labelled derivatives of low‐density lipoprotein for radiopharmaceutical use
Authors: Moerlein S. S. , Dalal K. K. , Yano Y.
Published: October 2006

The syntheses of two analogues of low‐density lipoprotein (LDL) labelled with 123I or 131I was optimized for radiopharmaceutical application. Rabbit LDL was employed due to its usefulness in pre‐clinical experimentation, although the parameters which were optimized also pertain to human LDL. LDL was iodinated directly with exchange‐labelled [123I]ICI to produce injectable [123I]LDL in 40% radiochemical yield within 30 min. A derivatized version of LDL, [123I]TC‐LDL, was produced in about 30% radiochemical yield within 75 min by radioiodination of tyramine‐cellobiose (TC) via in situ oxidation of 123I− followed by cross‐linking to LDL using cyanuric chloride. Quality control tests indicated that both radioiodinated LDL and TC‐LDL were very similar in character to the native LDL molecule.
Synthesis of carbon‐14 labelled spiro‐piperidyl‐rifamycins (LM 118) and rifabutin (LM 427)
Authors: Fontana Erminia , Giarda Silvio , Vioglio Sergio , Vicario Gian Piero
Published: October 2006

Two syntheses of radiolabelled spiro‐piperidyl‐rifamycins are described.

. A five steps synthesis (Scheme 1) was performed to give 4‐deoxo‐3,4‐[2‐spiro‐(N‐[14C]methyl‐4‐piperidyl)]‐(1H)‐imidazo‐(2,5‐dihydro)‐rifamycin S ([14C]LM 118), in an overall radiochemical yield of ∼ 20%, 98% radiochemically pure and with a specific activity of 440 MBq/mmol (11.9 mCi/mmol) starting from [14C]methyl iodide 1.

. A three steps synthesis (Scheme 2) was performed to give 4‐deoxo‐3,4‐[2‐spiro‐(N‐2‐methyl[1‐14C]propane‐4‐piperidyl)]‐(1H)‐imidazo‐(2,5‐dihydro)‐rifamycin S ([14C] rifabutin) in an overall radiochemical yield of ∼38%, 97% radiochemically pure with a specific activity of 1.27 GBq/mmol (34.32 mCi/mmol). 1‐(2‐Methyl[1‐14C]propanoyl)‐piperazin‐4‐one ethylene ketal was employed as starting material.
Synthesis of tritium and deuterium labeled 8‐N‐n‐butyl‐N‐methylamino‐8‐(3‐hydroxyphenyl)‐1,4‐dioxaspiro[4,5]decane hydrochloride
Authors: Hsi Richard S. P. , Kurtz Richard R. , Moon Malcolm W.
Published: October 2006

The title compound, a 4‐amino‐4‐arylcyclohexanone derivative with central analgesic activity, was labeled with tritium at the C‐7 and C‐9 positions. Deuterium labeled intermediates were used as models for developing isotope exchange and synthetic procedures. Deuterium and tritium labeled title compounds were obtained in five steps with overall yields of 18‐22% from 1,4‐dioxaspiro[4,5]‐decan‐8‐one and 3‐bromophenol.
Synthesis of 5‐amino[carboxyl‐14C]salicylic acid
Authors: Jørgensen Ole , Petersen Susanne , Carlsen Lars
Published: October 2006

Improvements have been made to the synthesis of 5‐aminosalicylic acid (5‐ASA) in order to make it applicable for the small‐scale synthesis of 5‐amino[carboxyl‐14C]salicylic acid.
Synthesis of 14C‐ and 3H‐labeled fluoxetine, a selective serotonin uptake inhibitor
Authors: Robertson David W. , Krushinski Joseph H. , Wong David T. , Kau Don
Published: October 2006

Fluoxetine (N‐methyl‐γ‐(4‐(trifluoromethyl)phenoxy)benzenepropanamine) is a potent, highly selective serotonin uptake inhibitor that is useful in treating a variety of major psychiatric derangements. We have synthesized this compound in 14C‐ and 3H‐labeled forms. The tritium label was introduced in the final step by catalytic dehalogenation of the brominated fluoxetine precursor 6. Reaction conditions could be controlled such that catalytic hydrogenolysis of the labile C‐O benzylic bond was minimized. Following HPLC purification, [3H]‐fluoxetine was obtained in a state of high radiochemical purity (98%) and specific activity (20.4 Ci/mmol). The 14C‐label was introduced in the final step via a nucleophilic aromatic substitution reaction between the sodium salt of α‐(2‐(methylamino)ethyl)benzenemethanol and uniformly ring‐labeled p‐chlorobenzotrifluoride. Following purification by flash chromatography, [14C]‐fluoxetine was obtained in 98.3% radiochemical purity with a specific activity of 5.52 mCi/mmol.
Syntheses of deuterium labeled bile alcohols
Authors: Kihira Kenji , Kosaka Daisaku , Une Mizuho , Hiraoka Toshihito , Kajiyama Goro , Hoshita Takahiko
Published: October 2006

The following major bile alcohols, identified in urine of healthy humans and in bile and urine of patients with cerebrotendinous xanthomatosis, were synthesized as internal standards for mass spectral analyses: [26,27‐D6]5β‐cholestane‐3α,7α,12α,25‐tetrol, [26,27‐D6](23S)‐5β‐cholestane‐3α,7α,12α,23,25‐pentol, [27‐D3]5β‐cholestane‐3α,7α,12α,25,26‐pentol, and [2,4‐D4]27‐nor‐5β‐cholestane‐3α,7α,12α24,25‐pentol.
Synthesis of a deuterium labeled variant of the rat hepatocarcinogen, methapyrilene
Authors: Kammerer R. Craig , Kloc Kenneth
Published: October 2006

Methapyrilene, I, once a commonly found antihistamimic drug, has been synthesized with four deuterium labels, three of which are on the thiophene ring. Initially, thiophene was deuterated by solvolysis of the tetramercuric acetate‐derivative with deuterium chloride. Carbonylation of the thiophene ring at the 2‐position, by the addition of dimethylformamide to the 2‐lithio‐derivative, gave [3,4,5‐d3] thiophene‐2‐carboxaldehyde. Condensation of this aldehyde with 2‐aminopyridine was followed by reduction of the resulting imine with sodium borodeuteride to yield the N‐([3,4,5‐d3]‐2‐thienyl[d]‐methylene)‐2‐aminopyridine, VIII. Alkylation of the lithium salt of VIII with dimethylaminoethylchloride gave N, N‐dimethyl‐N'‐[2‐pyridyl]‐N'‐([3,4,5‐d3]‐2‐thienyl‐[d]methylene)‐1,2‐ethane diamine, I, in good yield. Combustion analysis, 500 mHz NMR, and mass spectrometry confirmed the identity of the product which will be useful for metabolic studies.
Enhanced incorporation of nonhydrolyzable tritium in GnRH and TRF by catalytic exchange labeling
Authors: Oehlke J. , Mittag E. , Tóth G. , Bienert M. , Niedrich H.
Published: October 2006

Gonadotropin releasing hormone (GnRH), D‐Phe6‐GnRH and thyrotropin releasing factor (TRF) were tritiated by direct catalytic exchange using Rh/Al2O3 + HT under conditions which lead in model deuterations of Nα‐acetylhistidine amide to a high incorporation of deuterium into position 5 of the histidine ring. Specific activities up to a range of 400 GBq/mmol in form of nonhydrolyzable tritium are attainable after removal of the label incorporated into position 2 of the histidine ring. A crucial reason for diminished specific activities was found to be a catalystmediated hydrogen transfer between the peptides and traces of water, contained in the reaction mixture, competing with the tritiation.
A simple apparatus for reductive labelling with isotopic hydrogen gas at atmospheric pressure
Authors: Lockley William J S
Published: October 2006

A simple apparatus is described for the generation of isotopic hydrogen gas by acid‐catalyzed hydrolysis of sodium borotritide or borodeuteride. The apparatus may be conveniently utilized for isotopic hydrogen reductions of from 20 μmol to 1 mmol scale.
Synthesis and biological evaluation of p,p′‐dideuteriophenytoin
Authors: Poupaert Jacques H. , Guiot Pierre , Dumont Pierre
Published: October 2006

A reaction sequence is described to synthesize p,p′‐dideuteriophenytoin in three steps from commercially available starting materials. The deuterium content at best reached 99.2% as measured by mass spectrometry. For materials with isotopic content up to 95%, excellent agreement was found between the data obtained by mass spectrometry and 13C‐nuclear magnetic resonance operated in a NOE‐suppression mode. p,p′‐Dideuteriophenytoin was evaluated comparatively with phenytoin and p‐deuteriophenytoin in the maximal electroshock test. While all three compounds exhibited a high degree of antiepileptic activity, none of them demonstrated significant superiority over the others.
Synthesis of D/D‐norepinephrine‐ (phenyl‐U‐13C)
Authors: Weisz Adrian , Markey Sanford P.
Published: October 2006

The synthesis of phenyl‐U‐carbon‐13 labelled D,L‐norepinephrine from catechol‐U‐13C in three steps is described. In the first step, the Friedel‐Crafts acylation of the labelled part with N‐phthaloylglycylchloride yielded the aromatic ketone adduct. Subsequent hydrolysis and catalytic hydrogenation produced the desired product in a 5% overall yield.
Efficient syntheses of (±) [2‐2H2]mevalonolactone and (±) [2‐2H2]homomevalonolactone
Authors: Banerji Asoke , Kalena Govind P.
Published: October 2006

Efficient syntheses of (±) [2‐2H2]mevalonolactone and (±) [2‐2H2]homomevalonolactone involving condensations of lithiotrimethylsilyl [2‐2 H2]acetate with appropriate 3‐oxo‐alcohols are described. Regiospecificity of the label was established by NMR spectroscopy.
Synthesis of 14C‐ and 2H‐labeled (3S)‐1‐benzyl‐3‐pyrrolidinyl methyl (4S)‐2,6‐dimethyl‐4‐(m‐nitrophenyl)‐1,4‐dihydropyridine‐3,5‐dicarboxylate hydrochloride (YM‐09730‐5), a potent calcium antagonist
Authors: Arima Hideki , Tamazawa Kazuharu , Takeuchi Makoto
Published: October 2006

A potent and long acting calcium antagonist YM‐09730‐5, (3S)‐1‐benzyl‐3‐pyrrolidinyl methyl (4S)‐2,6‐dimethyl‐4‐(m‐nitrophenyl)‐1,4‐dihydropyridine‐3,5‐dicarboxylate hydrochloride (7a·HCl), was labeled with carbon‐14 and deuterium. The labeled materials were prepared by either the cyclizing Michael addition of 3‐aminocrotonate (5c) to benzylidene acetoacetate (6) or the modified Hantzsch reaction using m‐nitrobenzaldehyde, aminocrotonate(5a) and acetoacetate (3b). The 14C‐labeled material (7c·HCl) was synthesized from methyl [3‐14C]acetoacetate (4c) in a 32.0% radiochemical yield, at a specific activity of 60.9 mCi/mmol. The deuterium labeled material (7b·HCl) was synthesized from 1‐benzyl‐3‐hydroxypyrrolidine‐d4 (2b) which was obtained by the reduction of succinimide (1) with LiAlD4.
N.C.A. 18F‐fluoroacylation via fluorocarboxylic acid esters
Authors: Block Dirk , Coenen Heinz Hubert , Stöcklin Gerhard
Published: October 2006

The preparation and introduction of fluoroacyl moieties as prosthetic groups is described for n.c.a. labelling with fluorine‐18. Activation by the aminopolyether 2.2.2./K2CO3 complex was used for the nucleophilic 18F‐exchange in α‐substituted acid esters. Increasing yields were found in the sequence: iodo << chloro < tosyloxy < bromo. The methylester of α‐bromopropionic acid proved to be the best precursor for acylation. The [2‐18F]fluoropropionic acid methylester was prepared with radiochemical yields of > 90% within 10 minutes. It reacted effectively with primary alcohols in the presence of 3% methane sulfonic acid. Using n‐butylamine as model compound and O.1% NH4Cl as acid in aqueous solution, n.c.a. N‐fluoroacylation was also performed with > 80% radiochemical yield. This reaction is relevant to 18F‐labelling of biomolecules such as peptides.
Enantioselective synthesis of 11C‐labeled phenylethanolamine
Authors: Maeda Minoru , Nishimura Shuichi , Fukumura Toshimitsu , Kojima Masaharu
Published: October 2006

No‐carrier‐added [1‐11C]phenylethanolamine was prepared by the oxynitrilase‐catalyzed addition of hydrogen [11C]cyanide to benzaldehyde followed by reduction of the [11C]cyanohydrin. Radiochemical yields of 2‐4% at end‐of‐synthesis were obtained in a preparation time of 50‐60 min from the end of hydrogen [11C]cyanide production. The enantiomeric composition was determined through its conversion to the diastereomeric Mosher amide‐esters; the enantiomeric purity of the [11C]phenylethanolamine produced via NaBH4‐CoC12 reduction was 60% e.e. (R/S = 80/20) while that prepared through boran‐THF complex reduction was 80% e.e. (R/S = 90/10).
Synthesis of 13 C labelled unsymmetrically substituted maleic anhydrides
Authors: Breau L. , Kayser M. M.
Published: October 2006

Methylmaleic (citraconic) and ethoxymaleic anhydrides labelled with 13C at C‐4, and phenylmaleic anhydride labelled at C‐1 were prepared in excellent yields from inexpensive starting materials. The methodology described here can be applied in a synthesis of a variety of substituted maleic anhydrides.
Synthesis of 5‐,6‐, and 7‐deutero sparteines
Authors: Meese Claus O. , Ebner Thomas
Published: October 2006

Kinetically controlled1H/2H exchange at carbon atom 5 of (‐)‐1,6‐dehydrosparteinium monoperchlorate (3a) followed by sodium borohydride or sodium borodeuteride reduction of the iminium double bond gave optically active 5,5‐(2H2)‐sparteine (1b) and 5,5,6‐(2H3)‐sparteine (1c), respectively. Under thermodynamic control a third deuterium atom was incorporated into3at carbon atom 7. Borohydride reduction or rapid re‐exchange followed by reduction lead to the novel sparteine analogues 5,5,7‐(2H3)‐sparteine (1d) and 7‐(2H)‐sparteine (1e). The title compounds have been prepared in 76 to 83 % yield and 89 to 97 % isotopic purity.
[14C] – radiolabeling of {[trans‐(8β)]‐6‐methyl‐1‐(1‐methylethyl) ergoline‐8‐carboxylic acid, 4‐methoxycyclohexyl ester (Z)‐2‐butenedioate [(1:1)]. A potent and selective 5ht2‐receptor antagonist
Authors: Marzoni Gifford , Wheeler William J. , Garbrecht William L.
Published: October 2006

[14C]‐Labeled {[trans‐(8 β)]‐6‐methyl‐1‐(1‐methylethyl)ergoline‐8‐carboxylic acid, 4‐methoxycyclohexyl ester (Z)‐2‐butenedioate (1:1)} (LY281067) (10) was synthesized from unlabeled 6‐methyl‐1‐(1‐methylethyl)ergoline‐8‐carboxylic acid (2). The [14C] label was introduced into the carboxyl group attached to the 8 position of the ergoline nucleus. This site is stable to metabolism. The synthesis involves removal of the unlabeled carboxyl group from 2 and subsequent reinsertion of a [14C]‐labeled carboxyl group into the same position. The radiolabel is not introduced until near the end of the synthesis which allows for ease of handling and scale‐up of intermediates.
Preparation and characterization of 2‐deoxy‐2‐[18F] fluoro‐D‐galactose
Authors: Oberdorfer Franz , Traving Birgitt‐C. , Maier‐Borst Wolfgang , Hull William E.
Published: October 2006

2‐Deoxy‐2‐[18 F] fluoro‐D‐galactose was prepared using gaseous [18F]acetyl hypofluorite or [18F]F2 and tri‐O‐acetyl‐D‐galactal as substrate. The product was obtained in a surprisingly high epimeric purity (>90%), even with [18F]F2 as fluorinating reagent, as demonstrated by HPLC and high‐resolution 1H‐ and 19F‐NMR spectroscopy. This is the first report of a highly stereoselective reaction using molecular fluorine in a polar protic solvent. Epimerization at C‐3 of galactal led to α‐2‐deoxy‐2‐fluoro‐D‐idose and α‐2‐deoxy‐2‐fluoro‐D‐gulose as minor products. A simple apparatus for a partially remote‐controlled preparation of 2‐deoxy‐2‐[18F]fluoro‐D‐galactose is also described.
Synthesis of specific labelled [methyl‐14C]sarin
Authors: Chang Sin‐Ren A. , Riggio Gaetano , Hopff Wolfgang H. , Waser Peter G.
Published: October 2006

Synthesis of specific labelled [methyl‐14C]sarin. The synthesis of labelled [methyl‐14C]sarin, [14C]methylphosphonofluoridic acid 1‐methylethyl ester, was accomplished by another approach as for nonlabelled sarin in a tele‐conducted reaction vessel. The purity was estimated by IR, GC, and GC‐MS and the stability in different media was examined.
Synthesis of (5‐methyl‐2‐oxo‐1,3‐dioxol‐4‐YL)methyl 7‐[D‐O‐(L‐alanyl)[β‐14C]mandelamido]‐3‐[[(5‐methyl‐1,3,4‐thiadiazol‐2‐YL)thio]methyl]‐3‐cephem‐4‐carboxylate and its active compound
Authors: Nishizawa Susumu , Matsui Hiroshi , Ohkubo Akio , Kakeya Nobuharu , Kiritani Reiko
Published: October 2006

(5‐Methyl‐2‐oxo‐1,3‐dioxol‐4‐yl)methyl 7‐[D‐O‐(L‐alanyl)[β‐14C]‐mandelamido]‐3‐[[(5‐methyl‐1,3,4‐thiadiazol‐2‐yl)thio]methyl]‐3‐cephem‐4‐carboxylate (14C‐KY‐109) and its parent drug (14C‐KY‐087) were synthesized from D‐(‐)‐mandelic‐β‐14C acid prepared by optical resolution of DL‐(±)‐ mandelic‐β‐14C acid. The overall radiochemical yields were 16.2% for 14C‐KY‐087 and 49.6% for 14C‐KY‐109, based on D‐(‐)‐mandelic‐β‐14C acid. Both the products had radiochemical purities greater than 97% as measured by TLC.
Kit type labelling of [123I] metaiodobenzylguanidine
Authors: Dougan H. , Lyster D. M. , Vincent J. S. , Rihela T.
Published: October 2006

We have examined the labelling of [123I] MIBC by a Cu(I) catalyzed reaction in aqueous solution. We regularly obtained >99% radiochemical purity [123I] MIBC product and >97% radiochemical yield. At 100°C with 2 mg MIBG the radiochemical purity reached 85% at 2.5 min, 97% at 5 min and 99% at 10 min through 30 min. With 200 μg MIBG the reaction proceeded at roughly one tenth the former speed. Many details of technique were essential; the highlights were use of dry triturated reagents and the use of H2SO4 solvent. Neglect of proper procedure led to low radiochemical yields and 123I bound to apparatus. The procedure has been utilized with up to 1.0 mL 123I (0.1N NaOH) or 93 mCi 123I. A study of temperature dependence showed that the reaction proceeded readily, albeit more slowly at 20°C. The temperature coefficient at 100°C was estimated ∼1.7.
Synthesis of (5R,6S)‐6‐[(1R)‐hydroxyethyl]‐3‐[1‐methylpyridinium‐2‐YL‐methanethio]‐[3‐14C]‐7‐oxo‐1‐azabicyclo[3.2.0]hept‐2‐ene‐2‐carboxylate
Authors: Swigor J. E. , Kim C. U. , Pittman K. A.
Published: October 2006

The synthesis of the title compound (4) is described. Treatment of (3S)‐[(1R)‐hydroxyethyl]‐(4R)‐[3‐(p‐nitrobenzyloxy) carbonyl‐2‐oxo‐[2‐14C]‐3‐diazopropan‐1‐yl]azetidin‐2‐one1 with rhodium diacetate achieved ring closure forming (5R,6S)‐p‐nitrobenzyl‐6‐[(1R)‐hydroxyethyl]‐3,7‐dioxo‐[3‐14C]‐1‐azabicyclo[3.2.0]heptane‐2‐carboxylate (1). Reaction with diphenylchlorophosphate followed by 2‐(mercaptomethyl) pyridine under basic conditions produced (5R,6S)‐p‐nitrobenzyl‐6‐[(1R)‐hydroxyethyl]‐3‐(pyridine‐2‐yl‐methanethio)‐[3‐14C]‐7‐oxo‐1‐azabicyclo[3.2.0] hept‐2‐ene‐2‐carboxylate (2). Formation of the quaternary compound with methyl fluorosulfonate and deprotecting the acid by hydrogenolysis gave the title compound (4) in 6% overall radiochemical yield.
Synthesis of deuterium‐labelled viloxazine
Authors: Mamada Kumiko , Furuta Takashi , Kasuya Yasuji
Published: October 2006

The synthesis of deuterium‐labelled viloxazine with high isotopic purity is described. The synthetic procedures employ alkylation of 2‐(benzyloxy)phenol with [2H5]ethyl iodide for the introduction of deuterium. Catalytic removal of the benzyl group of the deuterated product followed by reaction with epichlorohydrin afforded 1,2‐epoxy‐3‐(2′‐pentadeuteroethoxyphenoxy)propane. Addition of 2‐aminoethyl hydrogen sulphate to the epoxide and subsequent ring formation into a morpholine derivative produced the desired [2H5] viloxazine.
Synthesis of [5‐3H] hemimellitic acid
Authors: Shimoni Michael , Azran Jacques , Buchman Ouri
Published: October 2006

1,2,3‐Benzenetricarboxylic acid (hemimellitic acid) tritiated in position 5 has been labelled at a specific activity of 16.2 Ci/mmol, starting from 3‐bromo naphthalic anhydride. Attempts at direct bromination of the acid followed by tritiodebromination, or of general labelling by hydrogen‐tritium exchange gave poor results.
A new synthesis of 2‐deoxy‐2‐[18f]fluoro‐D‐galactose using [18f]fluoride ion
Authors: Haradahira Terushi , Maeda Minoru , Kai Yasunobu , Kojima Masaharu
Published: October 2006

A nucleophilic radiofluorination of methyl 3,4‐0‐isopropylidene‐2‐0‐(trifluoromethanesulfonyl)‐6‐0‐trityl‐β‐D‐ talopyranoside (1) with aminopolyether (Kryptofix 2.2.2.) supported potassium [18F]fluoride in acetonitrile gave methyl 2‐deoxy‐2‐(18F) fluoro‐3,4‐o‐isopropylidene‐6‐0‐trityl‐β‐D‐galactopyranoside (2). Hydrolysis of 2 with 6N HCl followed by passage through an ion retardation resin column and a neutral alumina column gave 2‐deoxy‐2‐[18F]fluoro‐D‐galactose (2‐18FDGal) in 36–39% overall radiochemical yield without correction for decay. The total preparation time was about 90 min from start of the radiofluorination.
Carbon‐14 methylation of the 2‐methylbutyryl side chain of mevinolin and its analogs
Authors: Prakash S. R. , Ellsworth R. L.
Published: October 2006

A one step procedure for the preparation of labeled mevinolin analogs 4, 10 and 15 possessing the 2,2‐dimethylbutyryloxy side chain is described. The lactones 1, 7 and 13 were converted into potassium salts of their corresponding di or trihydroxy carboxylic acids from which anionic ester enolates were generated and alkylated with [14C]methyl iodide. Workup and purification by reverse phase HPLC provided radiochemically pure 4, 10 and 15. The labeled lactones were converted into ammonium salts of their corresponding di or trihydroxy acids.
Radioiodinated aliphatic amines as potential pulmonary imaging agents: III. Synthesis of 6‐[131i]‐iodohexylamine and its β‐alkyl substituted analogues
Authors: Gopalakrishna G. , Lee Y. W. , Selvaraj S. , Abrams D. N. , Man S. F. P. , Noujaim A. A.
Published: October 2006

The aliphatic amines, 2‐methyl‐ and 2‐isopropyl‐ substituted 6‐hydroxy −1 ‐hexylamines were synthesized from ethyl‐6‐hydroxyhexanoate in 22% and 11% overall chemical yield respectively. 6‐hydroxy‐ 1 ‐hexylamine was available commercially. 6‐hydroxy −1 ‐hexylamine and its 2‐methyl‐ and 2 ‐isopropyl‐ substituents were successfully radioiodinated with trimethylsilyl polyphosphate and [131I]‐Nal/Nal to afford the corresponding 6‐[131I]‐labelled amines in 67%, 61% and 55% radiochemical yield respectively and greater than 98% radiochemical purity (specific activity 340 GBq mmol−1).
Synthesis of perdeuterio‐1,4‐diazabicyclo[2,2,2]octane (DABCO‐2H12)
Authors: Gorman A. A. , Standen M. C.
Published: October 2006

1,4‐Diazabicyclo[2,2,2]octane (DABCO) is an efficient quencher of singlet oxygen, O2(1Δg), and is used as an indicator of O2(1Δg) intermediacy in both chemical and biochemical oxidative processes. The quenching is physical in character and the fully deuteriated derivative, DABCO‐2H12, is a molecule of potential mechanistic importance. Its synthesis with >98% isotopic purity is described.
Method for synthesis of 2‐azido‐N(6)‐m‐tritiobenzylaminopurine, a photoaffinity label for cytokinin‐binding proteins in plants
Authors: Cooper Geoffrey , Bourell James , Kaminek Miroslav , Fox J. Eugene
Published: October 2006

A method for tritiation of 2‐azido‐N(6)‐benzyladenine (AZBA), a photoaffinity analog of the plant hormone N(6)‐benzyladenine (BA), was developed. The synthetic sequence involves condensation of 2,6‐dichloropurine with m‐iodobenzylamine to yield 2‐chloro‐N(6)‐m‐iodobenzyladenine, followed by selective hydrodeiodination with tritium gas over palladium catalyst in pyridine solution to give 2‐chloro‐N(6)‐m‐tritiobenzyladenine. The known conversion of this compound to AZBA enables preparation of the photoaffinity label compound with specific activity high enough to permit detection of cytokinin‐binding proteins existing at low concentrations in plant tissues.
Syntheses of 1,4‐butanediamine‐1,1,4,4‐d4, 1,4‐butanediamine‐2,2,3,3‐d4, and their respective bis(ammonium nitrate) salts
Authors: Marchand Alan P. , Satyanarayana N. , McKenney Robert L. , Struck Stephen R.
Published: October 2006

Syntheses of the title compounds from diethyl succinate and from dimethyl acetylenedicarboxylate in 16% and 18% overall yield, respectively, are described; a procedure for converting these specifically deuterated diamines into the corresponding bis(ammonium nitrate) salts in 62% and 60% yield, respectively, is presented.
The synthesis of tritium‐labelled azidothymidine
Authors: Aggarwal Sunil K. , Shalinsky David R. , Agrawal Krishna C.
Published: October 2006

The synthesis of 3H‐labelled azidothymidine (AZT) from [methyl‐3H]thymidine is described. Purification of labelled AZT was accomplished by column chromatography. The purity of the labelled compound was determined by high performance liquid chromatography connected with a radioactive flow detector. The labelled AZT was found to be stable at pH ranging from 2.3 to 7.4 at 37°C and at hyperthermic temperature of 42°C.
A new synthesis of double labelled [4,6‐13C2] mevalonolactone
Authors: Zamir Lolita O. , Lin Mubin , Nguyen Cong‐Danh
Published: October 2006

The chemical synthesis of double labelled mevalonolactone with carbon 13C at positions C‐4 and C‐6 is reported.
Syntheses of carbon‐14 and tritium labelled forms of bupropion hydrochloride – a novel antidepressant
Authors: Hill John A. , Scharver Jeffrey D.
Published: October 2006

Bupropion hydrochloride 1 (2‐tert‐butylamino‐3′‐chloropropiophenone hydrochloride) was synthesized in the [14C]‐labelled form with specific activity 36.5 mCi/mmol suitable for drug metabolism, distribution and pharmacokinetic studies. The drug was synthesized in the [3H]‐labelled form with specific activity 20.5 Ci/mmol suitable for development of a radioimmunoassay procedure.
Synthesis of optically pure deuterium‐labelled nicotine, nornicotine and cotinine
Authors: Jacob Peyton , Benowitz Neal L. , Shulgin Alexander T.
Published: October 2006

We describe methods for the synthesis of enantiomerically pure (S)‐nicotine‐3′,3′‐d2. (S)‐nornicotine‐3′,3′‐d2, and (S)‐cotinine‐4′,4′‐d2. The key intermediate was 5‐bromomyosmine, which underwent base catalyzed exchange with deuterium oxide to give 5‐bromomyosmine‐3′,3′‐d2 with > 99% incorporation of label. This intermediate was reduced to (±)‐5‐bromonornicotine‐3′,3′‐d2 with sodium borohydride, resolved, and converted to (S)‐nornicotine‐3′,3′‐d2 by reductive debromination with hydrogen and a palladium catalyst. Reductive alkylation with formaldehyde and sodium borohydride provided (S)‐nicotine‐3′,3′‐d2. which was converted to (S)‐cotinine‐4′,4′‐d2 by reaction with bromine followed by zinc reduction. The deuterium label is located at positions that are not attacked in the major routes of mammalian metabolism of these alkaloids. Syntheses of tetradeuterated analogs of nicotine and cotinine and a pentadeuterated analog of nicotine, in which additional deuterium atoms are incorporated in the methyl groups, are also reported.
Tritium labelling of antitumor DNA bis‐intercalators: Synthesis of [3H] ditercalinium
Authors: Léon P. , Garbay‐Jaureguiberry C. , Le Greneur S. , Besselièvre R. , Roques B. P.
Published: October 2006

Ditercalinium : 2,2′‐[4,4′‐bipiperidine‐1,1′‐bis (ethane‐1,2‐diyl)] bis (1O‐methoxy‐7H‐pyrido[4,3‐c] carbazolium) tetramethanesulfonate (NSC 366241) is a potent antitumor DNA bis‐intercalator characterized by a new mechanism of action. In order to elucidate its biological action at the cellular level and its pharmacokinetic and metabolic properties, radiolabelled ditercalinium was prepared. In the present paper, we report the synthesis of the 11‐bromo‐1O‐methoxy‐7H‐pyrido [4,3‐c] carbazole presursor and its reductive tritiation by exchange with [3H]2. The pyrido[4,3‐c]carbazole ring labelled in position 11 is then condensed either with the 1,1′ bis (2‐chloroethyl)‐ 4,4′‐bipiperidine chain to provide tritiated ditercalinium or with the 1‐(2‐chloroethyl) piperidine chain to yield its monomeric analog.
A convenient one‐pot synthesis of 2,5‐anhydro‐3,4,6‐tri‐O‐benzoyl‐D‐[1‐14C]allononitrile, and its conversion to methyl 2‐β‐D‐ribofuranosyl‐4‐[2‐14C]selenazolecarboxylate
Authors: Woo Peter W. K.
Published: October 2006

Reaction of 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (3) with [14C]cyanotrimethylsilane, generated in situ by reaction of potassium [14C]cyanide and chlorotrimethylsilane in the presence of sodium iodide and 2,6‐lutidine, gave 2,5‐anhydro‐3,4,6‐tri‐O‐benzoyl‐D‐[1‐14C]allononitrile (4). Sequential reaction of the latter with hydrogen selenide, ethyl bromopyruvate, and methanolic sodium methoxide gave methyl β‐D‐ribofuranosyl‐4‐[2‐14C]selenazolcarboxylate (7), penultimate precursor to [2‐14C]CI‐935, or 2‐β‐D‐ribofuranosyl‐4‐[2‐14C]selenazolecarboxamide (8).
Synthesis of [14C]ciladopa
Authors: Hicks D. R. , Dolak L. , Foss D.
Published: October 2006

[14C]Ciladopa (S(−)‐2‐[4‐[[2‐14C]‐2‐hydroxy‐2‐(3,4‐dimethoxyphenyl)ethyl]‐1‐piperazinyl]‐2,4,6‐cycloheptatrien‐1‐ one hydrochloride; AY‐27,110 hydrochloride) has been synthesized in six steps incorporating [14C]carbon dioxide. [7‐14C]Acetoveratrole, obtained from veratric acid via the acid chloride, was brominated and coupled with a troponylpiperazine salt. The resulting ketone was stereospecifically reduced microbiologically to give the S(−) enantiomer of the corresponding alcohol. Two batches of [14C]ciladopa were produced, giving a combined overall yield of 25% from [14C]barium carbonate (sp. act. 44.7 ± 0.6 and 43.4 ± 0.8 μCi/mg; 99.2 and 98.9 % radiochemical purity, respectively).
Synthesis of tritiated ciprofibrate
Authors: Johnston D. , Ormiston R. A. , Slowey P. D.
Published: October 2006

A synthetic procedure for [3H]ciprofibrate is described. The radiolabel was introduced by catalytic dehalogenation of bromociprofibrate with tritium gas, as shown in the Scheme.
Synthesis of 13C, 14C and 2H13C labeled adrenoceptor antagonists: 6‐chloro‐2,3,4,5‐tetrahydro‐3‐methyl‐1H‐3‐benzazepine hydrochloride and its N‐desmethyl analog
Authors: Villani A. J. , Etzkorn F. , Rotert G. A. , Heys J. R.
Published: October 2006

The compound 6‐chloro‐2,3,4,5‐tetrahydro‐3‐methyl‐1H‐3‐benzazepine (SK&F 86466) was prepared in phenyl‐U‐14C and phenyl‐13C6 labeled forms in a six step sequence beginning with the appropriately labeled benzenes. In addition, the N‐desmethyl analog of the carbon‐14 labeled isotopomer and the N‐methyl‐2H3 derivative of the carbon‐13 isotopomer were prepared via the N‐(2,2,2‐trichloroethyl) carbamates by hydrolysis and lithium aluminum deuteride reduction, respectively.
The synthesis of [3H]cadralazine of high specific activity
Authors: Brundish Derek E. , Kane Peter D.
Published: October 2006

The title compound has been prepared by two different approaches. The first involved a five‐stage “hot” synthesis where the tritiation step was selective debromination of a cyclic β‐bromo‐α‐β‐unsaturated ketone. The double bond was protected by formal aromatisation. The absolute structure of this intermediate was determined by 3H‐FTNMR spectroscopy of its reduction product. Cadralazine was also labelled in its side chain by reduction of the appropriate ketone with high specific activity sodium borotritide. Both labelled products had specific activities of 18 Ci/mmol and radiochemical purities of 90–96%.
Syntheses of [4‐14c] and [6‐14c]nisoldipine
Authors: Scherling D. , Pleiß U.
Published: October 2006

The synthesis of [4‐14C]nisoldipine started from dimethyl [14C]formamide which was allowed to react with 2‐nitrophenyllithium yielding 2‐nitro[7‐14C]benzaldehyde. Knövenagel condensation with isobutyl acetoacetate yielded isobutyl 2‐(2‐nitro[7‐14C]benzylidene) acetoacetate. Key reaction step was the cyclizing Michael addition with methyl 3‐aminocrotonate to obtain 3‐isobutyl 5‐methyl 1, 4‐dihydro‐2, 6‐dimethyl‐4‐(2‐nitrophenyl)‐[4‐14C]pyridine‐3,5‐dicarboxylate (= [4‐14C]nisoldipine).

Starting material of the synthesis of [6‐14C]nisoldipine was barium[14C]carbonate which was converted to [1‐14C]acetyl chloride. The acid chloride was condensed with Meldrum's acid (2,2‐dimethyl‐1, 3‐dioxane‐4,6‐dione). The resulting intermediate was treated with boiling methanol to give methyl [3‐14C]acetoacetate. Reaction of the ß‐ketoester with gaseous ammonia in toluene afforded the corresponding aminocrotonate, which was condensed with isobutyl 2‐(2‐nitrobenzylidene)‐acetoacetate to yield [6‐14C]nisoldipine.
Photochemical synthesis of deuterium labelled 4‐N‐substituted cytosines
Authors: Celewicz Lech , Spychała Jarosław , Golankiewicz Krzysztof
Published: October 2006

The efficient photochemical method for the preparation of 4‐N‐(1‐deuterio‐alkyl)cytosines using as precursors 4‐N‐(1‐carboxy‐alkyl)cytosines is described.
Synthesis [4‐14C]‐ and [6,7‐D2]trilostane
Authors: Jonston D. , Elder D.
Published: October 2006

A synthetic procedure for producing [6,7‐d2]trilostane is described. The synthesis was accomplished in 6 steps from androsta‐4,6‐dien‐3,17‐dione with the label being introduced by catalytic deuteration. The synthetic procedure, using [4‐14C]testosterone, gave the required [4‐14C]trilostane in four steps.
Semi‐micro conversion of isotopically enriched water to dioxygen and carbon dioxide
Authors: Woolf A. A.
Published: October 2006

The quantitative conversion of heavy water on the decigram scale to dioxygen and carbon dioxide via the following sequence
U + 2D2O18 = UO218 + 2D2; UO + 2BrF3 = UF6 + Br2 + O and C + O = CO is described in detail. The reasons for choosing this particular route are outlined.
Synthesis of tritium‐labelled stobadine, a new cardioprotective agent
Authors: Marko Vladimir , Filip Jiří , Uhrín Dušan , Trnovec Tomáš , Beneš Luděk
Published: October 2006

Synthesis of dihydrochloride of (−)‐cis‐2,8‐dimethyl‐6‐[3H]‐2,3,4,4a,5,9b‐hexahydro‐1H‐pyrido[4,3b]indole by catalytic reductive dehalogenation of dihydrochloride of (−)‐cis‐2,8‐dimethyl‐6‐bromo‐2,3,4,4a,5,9b‐hexahydro‐1H‐pyrido[4,3b]indole is described together with the reaction conditions of the tritiation using 5% Pd/BaSO4 (UVVVR) in 0.1 M phosphate buffer pH 7.4. Specific activity of the product was 0.9 TBq.mmol−1, its radiochemical purity 96%.
Labelling of ochratoxins with 3H or 125I
Authors: Schmiedová D. , Vereš K. , Černý B. , Ruprich J. , Němeček J.
Published: October 2006

Catalytic hydrogenation of ochratoxin A by carrier‐free tritium was used to prepare 3H‐ochratoxin B with a high specific activity. Iodination of ochratoxin B by carrier‐free Na125I using the chloramine method yielded 125I‐ochratoxin with a high specific activity. Another 125I‐derivative of ochratoxin A was prepared by iodination of an ochratoxin A ‐ L‐tyrosine‐methylester conjugate. All three radioactive preparations were found to be useful for radioimmunoassay.
Synthesis of D‐threo‐2,2‐[37Cl2]dichloro‐N‐[β‐hydroxy‐α‐(hydroxymethyl)‐4‐nitrophenyl]acetamide ([37Cl2]chloramphenicol)
Authors: Jacquemijns Marjorie , Stavenuiter Johannus F. C. , Zomer Gijsbert
Published: October 2006

[37Cl2]Chloramphenicol was synthesized from D‐threo‐2‐amino‐1‐(4‐nitrophenyl)‐1,3‐propanediol and ethyl[37Cl2]dichloroacetate. Ethyl [37Cl2]dichloroacetate was prepared by chlorination with 37Cl2 of ethyldiazoacetate. 37Cl2 was obtained by reaction of a solution of Na37Cl in 30% hydrogen peroxide with fuming sulfuric acid. The overall yield (from Na37Cl) was 36%.
Facile synthesis of 1‐nitropyrene‐d9 of high isotopic purity
Authors: Fatiadi Alexander J. , Hilpert Laurence R.
Published: October 2006

1‐Nitropyrene‐d9, 1,3‐dinitropyrene‐d8, 1,6‐dinitropyrene‐d8, and 1,8‐dinitropyrene‐d8, used as internal standards for the determination of nitropolycyclic aromatic hydrocarbons (NPAH) in simple and complex mixtures, and required for GC/MS measurements used in the certification of NBS Standard Reference Material (SRM) 1596 (a mixture of nitropyrenes), were synthesized in one step from commercially available pyrene‐d10 and nitric acid‐d1. The electron impact mass spectra and isotopic purity of 1‐nitropyrene‐d9 and the deuterated dinitropyrenes were determined; the compounds were characterized by gas chromatpgraphy‐mass spectrometry (GC‐MS) and by high performance liquid chromatography (HPLC).
The preparation of 3‐Aminoxy‐1‐amino[1,1′‐3H2]propane
Authors: Pankaskie Marvin C. , Scholtz Stephen J.
Published: October 2006

3‐Aminoxy‐1‐aminopropane (APA) has previously been shown to be a potent inhibitor of the polyamine biosynthesis enzymes ornithine decarboxylase, adenosylmethionine decarboxylase, and spermidine synthase. Little information is known, however, regarding its mechanism of action, binding site mode(s), or cellular distribution. This report presents a relatively simple three step synthesis of 3‐aminoxy‐1‐amino[1,1′‐3H2]propane via the catalytic tritiation of 3‐aminoxypropionitrile hydrochloride. The latter compound has previously been described in the literature, albeit in little detail, but is included in this report for continuity.
A facile synthesis of δ‐aminolevulinic acid (ALA) regioselectively labeled with13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG)
Authors: Kurumaya Katsuyuki , Okazaki Takeo , Seido Nobuo , Akasaka Yuzuru , Kawajiri Yoshiki , Kajiwara Masahiro , Kondo Masao
Published: October 2006

δ‐Aminolevulinic acid (ALA), labeled with13C at position 1, 2, 3, 4, or 5, was synthesized from13C‐labeled glycine, Meldrum's acid, or bromoacetate. The latter compounds were prepared from13C‐sodium acetate or13C‐acetic acid. Enzymatic transformation from ALA to porphobilinogen (PBG) was directly observed by13C‐NMR.
The synthesis of (−), (+) and (±)‐[14C] SK&F 94836 a selective PDE III inhibitor
Authors: Armitage M. A. , Crowe A. M. , Lawrie K. W. M. , Rawlings D. A. , Saunders D. , Singh S.
Published: October 2006

SK&F 94836, a selective PDE III inhibitor is a positive inotropic agent with vasodilator activity. The syntheses of (‐)‐[N‐methyl‐14C]SK&F 94836, (+)‐[N‐methyl‐14C]SK&F 94836 and [carbonyl‐14C] SK&F 94836 are described. The racemate, labelled in the dihydropyridazinone heterocycle was obtained in 24.6% overall yield from K[14C]CN. The chiral compounds were radiolabelled by reacting a resolved precursor with [14C]methylamine.
Gehirn‐affine ruthenocen‐derivate: Chinuclidinol‐ester. Brain affinity of ruthenocene compounds: Quinuclidinol‐ester
Authors: Wenzel M. , Preiss D.
Published: October 2006

The ester of ferrocene carboxyl acid and quinuclidinol was synthesized, which after heating with 103RuCl3 yielded the labelled ruthenocenoyl‐ester. The organ distribution of this ester and of 103Ru‐labelled ruthenocenyl‐N(isopropyl)‐ethyl‐amin was studied in mice and rats and compared with the organ distribution of lodo‐labelled N(‐isopropyl)‐amphetamine. A high brain affinity was found and the ruthenocenoyl‐quinuclidinol‐ester showed a remarkable heart/blood ratio.
Radioiododestannylation. Convenient synthesis of a stable penicillin derivative for rapid penicillin binding protein (PBP) assay
Authors: Blaszczak Larry C. , Halligan Noreen G. , Seitz David E.
Published: October 2006

Radioiodination of p‐(trimethylstannyl)penicillin V with [125I]Na using a modification of the chloramine‐T method is simple, high yielding, and site‐specific. The structure and penicillin binding protein (PBP) affinity of p‐[125l]‐penicillin V (IPV) are similar to penicillin G and the product can be used directly without purification in the PBP assay. Because of the high degree of stability toward autoradiolysis and equivalent PBP binding affinity, IPV can be used in place of [3H]‐penicillin G or [14C]‐penicillin G for these experiments.
Synthesis of leukotrienes labelled with deuterium: [11,12,14,15‐2H4]‐LTA4 ‐LTC4, ‐LTD4 and ‐LTE4
Authors: Lellouche J. P. , Aubert F. , Noel J. P. , Boullais C. , Beaucourt J. P.
Published: October 2006

Semi‐hydrogenation by D2 gas on Lindlar catalyst of an acetylenic precursor led to [11,12,14,15‐2H4]‐LTA4 methyl ester 1a. Nucleophilic opening of the epoxide ring by amino thioacids afforded after saponification the corresponding deuterated peptidoleukotrienes LTC4, LTD4 and LTE4.
Preparation of 6‐deoxy‐D‐[U‐14C]glucose
Authors: Siglerová V. , Vereš K.
Published: October 2006

A synthesis of 6‐deoxy‐D‐[U‐14C]glucose is described. The compound, having a specific radioactivity of 912.6 MBq/mmol, was obtained in a 11.8 % overall radiochemical yield from the starting D‐[U‐14C]glucose.
Stoichiometric complexes tin‐methylenediphosphonate: Composition, biodistribution and elements of structure
Authors: Osinski P. , Poupaert J. , Gallez B. , Adline J. , Dumont P.
Published: October 2006

Stoichiometric methylenediphosphonate (MDP) complexes of tin were prepared and their composition was determined as Sn (II)‐(MDP)2 and Sn (IV)‐MDP. Biodistribution studies in mice have shown differences in organ uptake related to the valence of the metal ion and the nature of the injection solvent. N.M.R. spectra and gel filtration experiments indicated a simple, homogeneous structure for the stannous complex and the heterogeneous nature (hexa‐ and tetra‐coordinated) as well as a high apparent molecular weight for stannic species.
Enzymatic synthesis of [ribose‐U‐14C]8‐azaguanosine
Authors: Tozzi Maria Grazia , Camici Marcella , Corso Antonella Del , Ipata Pier Luigi
Published: October 2006

8‐Azaguanosine 14C‐labeled in the ribose moiety was enzymatically synthesized in two steps: 1) phosphorolytic cleavage of [U‐14C]inosine to yield [U‐14C]ribose‐1‐phosphate; 2) synthesis of 8‐azaguanosine from [U‐14C]ribose‐1‐phosphate and 8‐azaguanine catalyzed by purine nucleoside phosphorylase. The radiochemical yield was 70%, and no contaminants were present in the isolated radioactive nucleoside analog, as judged by HPLC analysis.
Synthesis of 5‐fluoroalkyl‐5‐methyloxazolidine‐2,4‐diones and their 18F‐labeled analogs as potential indicators of tissue pH
Authors: Maeda Minoru , Tatsuki Yoshihiko , Fukumura Toshimitsu , Kojima Masaharu
Published: October 2006

5‐Fluoromethyl‐, 5‐(2′‐fluoroethyl)‐ and 5‐(3′‐fluoropropyl)‐5‐methyloxazolidine‐2,4‐diones (4a,b,c) were prepared as potential indicators of tissue pH, based on the fluorinative dehydroxylation with diethylaminosulfur trifluoride and/or the displacement reaction with fluoride ion. 5‐(3′‐[18F]Fluoropropyl)‐5‐methyloxazolidine‐2,4‐dione (4d) was obtained by tosylate displacement in 14‐16% radiochemical yield in a synthesis time of 40 min from start of the radiofluorination. The other two congeners labeled with 18F resisted our efforts to prepare them using [18F]fluoride ion.
Synthesis of tritium labelled (–)–U50,488, a selective kappa opioid agonist
Authors: Thurkauf Andrew , De Gosta Brian , Rice Kenner C.
Published: October 2006

The preparation of 3H labelled (‐)‐trans‐3,4‐dichloro‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl) cyclohexyl]benzeneacetamide (U50,488) in four steps from N‐methylcyclohexylaziridine is described. The synthesis of the pharmacologically active (‐) isomer of U50,488 was accomplished through the resolution of the intermediate 2‐[1‐(3‐pyrrolinyl)]‐N‐methylcyclohexylamine using (+)‐mandelic acid.
Synthesis of tritium labelled sparsomycin
Authors: Van Den Broek Leon A. G. M. , Willemsen Kitty C. M. W. , Schlachter Irene H. G. , Ottenheijm Harry C. J. , Kaspersen Frans M.
Published: October 2006

The synthesis is described of tritiated sparsomycin (5), a broad‐spectrum antitumor antibiotic, with high specific activity (31.4 Ci/mmol, 1.16 TBq/mmol). The radiolabel was introduced by reduction of the cysteine methyl ester 1 with lithium borotritide. 3H NMR analysis of the final product showed the concomitant formation of the mono‐ and ditritiated compound in a ratio of 2:1.
Radiosynthesis of [11C]nifedipine and [11C]nicardipine
Authors: Wilson Alan A. , Dannals Robert F. , Ravert Hayden T. , Donald Burns H. , Lever Susan Z. , Wagner Henry N.
Published: October 2006

The radiosyntheses of the dihydropyridine (DHP) calcium channel blockers [11C]nifedipine and [11C]nicardipine by alkylation of the appropriate DHP 3‐monocarboxylic acid anion with [11C]iodomethane are described. Isolated radiochemical yields of 30–50% were obtained 25 minutes after the end‐of‐bombardment, with specific activities of 400–1400 mCi/μmol at the end‐of‐synthesis. A variety of positron emitting DHPs with different ester side chains in the 3 and 5 positions on the DHP ring may be prepared by this approach using currently available labelled alkylating agents.
Synthesis of [2‐14C]nimodipine
Authors: Scherling D.
Published: October 2006

[2‐14C]Nimodipine (8) was synthesized from isopropyl [3‐14C]acetoacetate (5), which was converted to isopropyl 3‐amino[3‐14C]crotonate (6) by reaction with gaseous ammonia in toluene. The 14C‐labelled drug 8 was prepared by the cyclising Michael addition of the 3‐aminocrotonate 6 onto 2‐methoxyethyl 2‐(3‐nitrobenzylidene)acetoacetate (7) in boiling ethanol.
Synthesis of [pyrrolidine‐14C]‐cotinine from 14C‐nicotine
Authors: Peeters R. , Daenens P.
Published: October 2006

The synthesis and purification of 14C‐cotinine is reported. 14C‐nicotine is converted into 14C‐dibromocotinine. Debromination of the latter results in 14C‐cotinine which is purified by high performance liquid chromatography.

The total radioactive yield of the synthesis is 44.8%. Starting from 500 μCi 14C‐nicotine, 224 μCi 14C‐cotinine is obtained with a specific activity of 0,23 mCi/mmol.
Synthesis of 1‐ethyl‐1‐(2‐hydroxyethyl)aziridinium‐1,2‐14C2 chloride (1) ([14C]AF64A)
Authors: Mistry Jehangir S. , Abraham Donald J. , Hanin Israel
Published: October 2006

1‐Ethyl‐1‐(2‐hydroxyethyl)aziridinium‐1,2‐14C2 chloride (1) ([(14C]AF64A), the labelled analogue of a selective presynaptic cholinotoxin, was prepared from labelled ethylene oxide. The synthetic intermediate, 1,2‐14C2‐2[ethyl[2‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]ethyl]amino]ethanol, obtained in good yield by the reaction of 2‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]diethylamine with [14C] ethylene oxide, was converted to the corresponding ethyl chloride derivative using CH3SO2Cl/n‐BuLi. Subsequent removal of the THP group under mild acidic condition gave the mono‐armed mustard as a stable hydrochloride salt in an overall chemical yield of 46% and radiochemical yield of 27%. Conversion of the mustard compound to the corresponding aziridinium species was followed by 1H NMR.
In‐vitro preparation of 113mIn (Ca)‐phytate colloid for liver scintigraphy
Authors: Al‐Janabi M. A. A.
Published: October 2006

A method for preparation' of in vitro radiocolloidal solution of 113mIn (Ca)‐phytate is reported. The radiochemical purity was determined using paper chromatography and it was higher than 95%. Liver uptake in mice was high (87%) with low lung uptake. This radiopharmaceutical has, therefore, medical disgnostic specifications.
Synthesis of tritium‐labelled natural prostaglandins of series 1,2,3
Authors: Shevchenko V. P. , Myagkova G. I. , Yu. Lazurkina T. , Dyomin P. M. , Shram S. I. , Zabolotsky D. A. , Yu. Nagayev I. , Belosludtsev Yu. Yu. , Evstigneeva R. P. , Myasoyedov N. F.
Published: October 2006

The complete chemical synthesis of unsaturated precursors of eicosanoids of series 1,2,3 is described. Selective hydrogenation by gaseous tritium of eicosapolyenoic acid acetylenic analogues was used to introduce the label into dihomo‐α‐linolenic, arachidonic and timnodonic acids, from which [3H]PGE, [3H]PGD and [3H]TXB2 were obtained by biosynthesis. From [3H]PGE multiply labelled PGA, PGB, PGFα, PGI2ME, 6‐keto‐PGF1αME were synthesized by chemical methods.
The effect of catalytic reaction conditions on the incorporation of tritium in unsaturated compounds
Authors: Shevchenko V. P. , Yu. Nagayev I. , Myasoedov N. F.
Published: October 2006

We have obtained multiple‐tritium‐labelled 5‐α‐androstan‐3‐one, dihydropicrotoxin, dimethyl‐propyl‐3‐chloro‐butyl‐ammonium chloride, 2,2‐di(trifluoromethyl)‐3,3‐dicyanobicyclohept[2,2,1]ane, dihydroalprenolol, undecanoic acid, dihydro‐m,m'‐di‐tert.‐butyl‐p‐coumaric acid and dihydrofusicoccin. By varying the conditions for the hydrogenation of terminal double bonds one can considerably increase the molar radioactivity of such compounds through isotopic exchange. We discuss some tentative explanations of the effect of the labelling reaction conditions upon the synthesis of compounds with desired properties.
Synthesis of 1‐(2,6‐difluorobenzoyl)‐3‐(2‐fluoro‐4‐(2‐chloro‐4‐trifluoromethylphenoxy) [ring‐U‐14C] phenyl)urea
Authors: Gillam Martyn G
Published: October 2006

1‐(2,6‐Difluorobenzoyl)‐3‐(2‐fluoro‐4‐(2‐chloro‐4‐trifluoromethylphenoxy) [ring‐U‐14C]phenyl)urea, a potent new acylurea insecticide and acaricide known as flufenoxuron, was labelled with carbon‐14 starting from o‐dinitro[ring‐U‐14C]benzene 1. 2‐Fluoronitro[ring‐U‐14C]benzene, 2 obtained by fluorination of 1 with n‐tetrabutylammonium fluoride, was converted in two stages to 4‐amino‐3‐fluoro[ring‐U‐14C]phenol 3, coupled with 3‐chloro‐4‐fluorobenzotrifluoride 4 to give 2‐fluoro‐4‐(2‐chloro‐4‐trifluoromethylphenoxy) [ring‐U‐14C]aniline 5, which when reacted with 2,6‐difluorobenzoylisocyanate 6 gave the required urea 7. [aniline ring‐U‐14C] flufenoxuron, having a specific activity of 851MBq/mmol (23mCi/mmol), was obtained in 24% overall radiochemical yield and a radiochemical purity of >99%.