bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of carbon‐14 labelled ethyl 2‐(P‐chlorophenoxy)‐2‐methyl propionate (CLofibrate; atromid‐S); clofibric acid and clofibric amide
Authors: Burns J.
Published: October 2006

The preparation of [14C] Ethyl 2‐(p‐chlorophenoxy)‐2‐methyl propionate (Atromid‐S; clofibrate) with the label separately located in three different positions is described, together with purification procedures employed. From each of the three labeled products, clofibric acid (CPIB acid;ICI 7132) has been prepared by hydrolysis. The labeled amide has also been synthesized.
1,3‐dihydroxybenzene‐2‐13C: Its preparation and reaction with chlorine and bromine in aqueous solution
Authors: Boyce Scott D. , Barefoot Aldos C. , Hornig James F.
Published: October 2006

1,3‐cyclohexanedione‐2‐13C was prepared by intramolecular Claisen condensation of methyl 5‐oxohexanote‐6‐13C with sodium methoxide. Formation of the ketoester starting material involved treatment of a mixed dicarboxylic anhydride with an isotopicallylabelled Grignard reagent, methyl‐13C magnesium iodide. Dehydrogenation of carbon‐13 labelled cyclohexanedione over a palladium/carbon catalyst produced 1,3‐dihydroxybenzene‐2‐13C. Chlorination and bromination of dihydroxybenzene in aqueous solution yielded isotopically‐labelled chloroform and bromoform, each having enriched carbon‐13 contents equivalent to that of the organic substrate.
An efficient synthesis of ethyne‐1‐13C
Authors: Colborn Robert E. , Vollhardt K. Peter C.
Published: October 2006

A synthesis of the title compound from 13CO2 is described. The final step utilizes lithium hexamethyldisilazide as a base in the double dehydrobromination of 1,2‐dibromoethane‐1‐13C. Some alternative procedures are discussed.
N‐succinimidyl propionate: Characterisation and optimum conditions for use as a tritium labelling reagent for proteins
Authors: Tang Yui S , Davis Ann‐Marie , Kitcher J Philip
Published: October 2006

N‐Succinimidyl propionate [NSP] was synthesised and characterised as a pale yellow waxy solid. Rates of hydrolysis in buffers range pH 5–9 were determined. Optimum conditions for reaction with lysine were within the range pH 7 to 8. A protein, wheat germ agglutinin was labelled at pH 7.5 at room temperature for two hours. Rates of reaction of other substrates under these conditions were investigated.
[14C]Senecionine and [14C]isosenecionine from the pyrrolizidine alkaloid retrorsine
Authors: Mattocks A. Robin
Published: October 2006

Retrorsine (1) has been oxidized to a mixture of two epimeric cyclic keto esters (2) which, [14C]methylmagnesium iodide gave [18‐14C]senecionine (3a) and [18‐14C] isosenecionine (3d).
Syntheses of 1‐dodecyl‐d25 phosphate
Authors: Sniegoski Lorna T. , White Edward
Published: October 2006

1‐Dodecyl‐d25 phosphate was prepared from commercially available 1‐dodecanol‐d26. The 1‐dodecanol‐d26 reacted with diphenyl phosphorochloridate to produce 1‐dodecyl‐d25 diphenyl phosphate, which was reduced with hydrogen in the presence of Adams catalyst to give a 58.9 percent yield of 1‐dodecyl‐d25 phosphate with 99.4 atom percent deuterium.
Synthesis of 195Au, 32P and 35S‐labelled auranofin, A novel orally effective gold antiarthritic drug
Authors: Hill David T. , Sutton Blaine M. , Levinson Sidney H. , Meier Joseph , Kline Smith
Published: October 2006

Auranofin (1), a phosphine gold(I) thiolate antiarthritic agent effective on oral administration, was labelled separately with 195Au, 32P and 35S. 195Au‐labelled auranofin 19 was made from H195AuCl4.3H20 via the intermediate chloro(triethylphosphine)gold‐195Au (18). Auranofin ‐35S (23) was prepared using thiourea‐35S. The synthetic routes for 19 and 23 were similar to those used for unlabelled 1. However, auranofin‐32p (28) was made by the novel, direct coupling of the 1: complex (2,3,4,6‐tetraO‐acetyl‐l‐thio‐β‐D‐glucopyranosato‐S)gold (27) with 32p(C2H5)3 (26) synthesized from 32PCl3 (24). The labelled compounds were used in pharmacokinetic, tissue distribution and metabolism studies.
D‐glucose derivatives labelled with 75,77Br and 123I
Authors: Kloster Gerd , Laufer Peter , Stöcklin Gerhard
Published: October 2006

Synthetic routes to D‐glucose derivatives labelled with either the positron emitter 75Br (T1/2 = 1.6 hr) or the single photon emitters 77Br (T1/2 = 56 hr) and 123I (T1/2 = 13.3 hr) in positions 2 or 3 were investigated in order to prepare useful tracers for glucose utilization studies in brain and heart.

3‐Deoxy‐3‐iodo‐D‐glucose and 3‐deoxy‐3‐bromo‐D‐glucose were prepared from 1,2:5,6‐di‐isopropylidene‐D‐allose via its triflate in 10‐20 % radiochemical yield.

2‐Deoxy‐2‐iodo‐D‐glucose and 2‐deoxy‐2‐bromo‐D‐glucose could not be prepared by the routes presented in this publication. On the route to these compounds, some intermediates of possible use as tracers for glucose utilization were prepared, namely the methyl glucosides methyl 2‐deoxy2‐iodo‐β‐D‐glucopyranoside (MIDG) and methyl 2‐deoxy‐2‐bromo‐β‐D‐glucopyranoside (MBDG) and the acetylated methyl glucosides methyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐iodo‐β‐D‐glucopyranoside (MTIG) and methyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐bromo‐β‐D‐glucopyranoside (MTBG). Radiochemical yields from 3,4,6‐tri‐O‐acetyl‐D‐glucal, halide ion and dichloramin T were 35 % for MTBG, 40 % for MTIG, 15 % for MBDG and 20 % for MIDG. Preparation times were less than 2 hours.
Quality control procedures in the preparation of 2‐deoxy‐D‐[1‐11C] glucose radiopharmaceutical
Authors: Vora Manhar M. , Boothe Thomas E. , Finn Ronald D. , Smith Patricia M. , Gilson Albert J.
Published: October 2006

Preparation and quality control of 2‐deoxy‐D‐[1‐11C] glucose (11C‐2DG, 1) have been accomplished by a combination of cation‐exchange and high performance liquid chromatography (HPLC) to give the radiopharmaceutical in greater than 99% radiochemical purity and an overall 25‐35% radiochemical yield in 45‐50 min. Quality control procedures utilizing GC and HPLC have been developed to determine not only chemical and radiochemical purity of the final product, but also to examine the reactants used and the products formed during the preparation of 1.
Tritium labelling of enkephalin analogs : Tyr‐D‐Ala‐Gly‐NH‐CH(CH3)‐CH2‐CH(CH3)2 (trimu 4), Tyr‐D‐Ser‐Gly‐Phe‐Leu‐Thr (DSLET), Tyr‐D‐Thr‐Gly‐Phe‐Leu‐Thr (DTLET), μ and δ opiate‐receptors specific ligands
Authors: Gacel G. , Dodey P. , Roques B. P. , Morgat J. L. , Roy J. , Fromageot P.
Published: October 2006

Unambiguous biochemical characterization of the different opiate receptors (i.e., μ and δ) imperatively requires fully specific and radiolabelled ligands. Therefore, in this paper, we report the synthesis of the 3,5‐dibromotyrosyl precursors of three highly selective peptides : Tyr‐D‐Ala‐Gly‐NH‐CH(CH3)‐CH2‐CH(CH3)2, TRIMU 4 (μ) Tyr‐D‐Ser‐Gly‐Phe‐Leu‐Thr, DSLET (δ) and Tyr‐D‐Thr‐Gly‐Phe‐Leu‐Thr, DTLET (δ). Reductive tritiation by exchange with 3H2 leads to the labelled enkephalins analogs in high yields and with specific activities between 45 to 60 Ci/mmole.
Preparation and purification of 77Br‐labelled p‐bromospiroperidol suitable for in vivo dopamine receptor studies
Authors: Dejesus Onofre T. , Friedman Arnold M. , Prasad Anita , Revenaugh James R.
Published: October 2006

An efficient and reliable method of preparing 77Br‐p‐bromo spiroperidol suitable for labelling dopamine receptors in vivo has been developed. This synthesis involves the reaction of 77Br−, H2O2, and spiroperidol in glacial acetic acid. The purity of the product was assured by the use of two column reverse phase high performance liquid chromatography. Radio‐chemical yields were in the range of 80–90%, while specific activities of 80–140 Ci/mmole were obtained at the end of the synthesis.
Synthesis of deuterium labelled perphenazine
Authors: Hawes E. M. , Gurnsey T. S. , Shetty H. U. , Midha K. K.
Published: October 2006

Procedures for the preparation of perphenazine‐d2, ‐d4, and ‐d6, and N‐deshydroxyethylperphenazine‐d4 and ‐d6 are described. Deuterium was introduced in the propylpiperazine side chain by treatment of the appropriate ester or imide with lithium aluminum deuteride. The γ‐carbon of the propyl group was labelled with two deuterium atoms by reduction of 2‐chloro‐10‐(2‐methoxycarbonylethyl)‐10H‐phenothiazine, while four deuterium atoms were incorporated into the piperazine ring by reduction of 2‐chloro‐10‐[3‐(3,5‐dioxo‐1‐piperazinyl)‐propyl]‐10H‐phenothiazine.
Synthesis of 14C‐labeled 5‐[1‐hydroxy‐2‐[2‐(o‐methoxyphenoxy) ethylamino] ethyl]‐2‐methylbenzenesulfonamide hydrochloride (YM‐09538)
Authors: Arima Hideki , Tamazawa Kazuharu
Published: October 2006

Preparation of the title compound, a novel antihypertensive agent, is described. The labeled material with a specific activity of 4.76 mCi/mmol was synthesized in a 50.6% radiochemical yield from [U‐14C]ethylene oxide via a process of six steps.
One‐pot procedure for the preparation of 14C ‐labelled trisodium phosphonoformate hexahydrate (foscarnet)
Authors: Gawell Lars
Published: October 2006

Trisodium phosphono[14C]formate is synthesized from [14C]phosgene in 4 steps. All reactions are performed in situ in an overall radiochemical yield of 51%.
The synthesis of (3H)‐xylamine, an irreversible inhibitor of norepinephrine uptake
Authors: Ransom R. W. , Kammerer R. C. , Cho A. K.
Published: October 2006

Xylamine [N‐(2‐chloroethyl)‐N‐ethyl‐2‐methylbenzylamine], an irreversible inhibitor of neuronal norepinephrine uptake, has been synthesized with tritium incorporated in the aromatic nucleus. Initially, 2‐methylbenzyl bromide was nonselectively mono‐brominated on the ring and the resulting isomeric products were condensed with 2‐(ethylamino)ethanol. Unequivocal identification of the products of each reaction was provided by mass spectral analysis. A mixture of mono‐bromobenzylamine isomers was isolated for catalytic reduction with 3H2 at a commercial facility. Carrier N‐(2‐hydroxyethyl)‐N‐ethyl‐2‐methylbenzylamine was added to the crude tritiated product prior to refluxing in the presence of excess thionyl chloride. (3H)‐Xylamine was obtained as the hydrochloride salt and repeated recrystallizations yielded a radiochemically pure product with a specific activity of 3.09 Ci/mmol. Several analytical procedures established that the radiolabel was associated with xylamine.
Synthesis of trideuterated stanozolol labelled selectively at the 17‐methyl group
Authors: Johnston D. , Henderson K.
Published: October 2006

A synthetic procedure for stanozolol‐d3is described. Deuterium labelling was achieved by the Grignard reaction of androstan‐3β ‐ ol ‐ 17 ‐ one with deuterium labelled methyl magnesium iodide (CD3Mg I). The synthesis was achieved in five steps from Δ5‐androstan‐3‐β‐ol‐17‐one in an overall yield of 15%. The procedure resulted in a product which was selectively deuterated and chemically pure.
Tritium labelling of antidepressants with regard to their chemical structure
Authors: Buchman Ouri , Azran Jacques , Shimoni Michael
Published: October 2006

Different methods of tritium incorporation have been applied to 14 available tricyclic antidepressant drugs. The specific activities of the labelled compounds are compared. The results are discussed by comparison with hydrogendeuterium exchange and with regard to the chemical structure of these derivatives.
The synthesis of 1‐[(1‐methylethyl) amino]‐3‐{[(4‐methyl‐thio)‐1‐naphthalenyl]OXY}‐2‐propanol hydrochloride‐naphthalene‐1114C: 4′‐methylthiopropranolol
Authors: Gransden D. F. , Roth G. A. , Takahashi I. T.
Published: October 2006

The antihypertensive drug, 1‐[(1‐methylethyl)amino]‐3‐{[(4‐methylthio)‐1‐naphthalenyl ]oxy} ‐2‐propanol hydrochloride has been labeled with carbon‐14 in the 1‐position of the naphthalene. A total of 18.76 mCi was prepared in five steps starting with 1‐naphthol‐1‐14C. The overall yield for the synthesis was 33.6% following five recrystallizations of the free base. The radiochemical purity of the hydrochloride product was 98.0% by high pressure liquid chromatography (HPLC)/liquid scintillation counting (LSC). The specific activity of the product was found to be 11.68 ∓ 0.45 mCi/mmole. Structural confirmation was done by infrared spectroscopy.
Regioselective deuteration kinetics of 2,3,6‐trimethyl‐4‐phenylpyrylium and 2,6‐dimethyl‐3,4‐diphenylpyrylium salts (1)
Authors: Balaban Alexandru T. , Balaban Teodor Silviu , Uncuta Cornelia , Gheorghiu Mircea D. , Chiraleu Filip
Published: October 2006

The deuteration of 2,3,6‐trimethyl‐4‐phenylpyrylium salts in D2O + D3CCN indicates that the 2‐methyl group is deuterated 3.3 times faster than the 6‐methyl group. The 1H‐NMR assignment is based on an unambiguous synthesis of the 2‐CD3‐congener; similar assignments were made for 2,3,6‐trimethyl‐4‐phenylpyridine, and lanthanide‐induced shifts were determined. The deuteration of 2,6‐dimethyl‐3,4‐diphenylpyrylium perchlorate in anhydrous HCOOD + NaOOCH (the assignment in 1H‐NMR spectra is straightforward owing to the shielding of 2‐methyl protons by the neighbouring orthogonal phenyl group) indicates similarly that the 2‐methyl group is deuterated 3.0 times faster than the 6‐methyl group. Though the relative rates for 2‐ and 6‐methyl groups do not differ sufficiently for preparative regioselective deuterations, the present findings raise interesting problems for M.O. calculations.
Derivatives of β‐adrenergic antagonists. Preparation of propranolol‐3,3‐2H2 and propranolol‐18O
Authors: Nelson Wendel L. , Bartels Michael J.
Published: October 2006

Syntheses of 1‐(isopropylamino)‐3‐(1‐naphthoxy)‐2‐propanol‐3,3‐2H2 (propranolol‐3,3‐2H2) (1) and of 1‐(isopropylamino)‐3‐(1‐naphthoxy‐180)‐2‐propanol (propranolol‐180) (2) are described. Reaction of 1‐naphthol (3) with glycerol‐2,3‐acetonide‐1,1‐2H2 tosylate (4) afforded, after hydrolysis, 3‐(1‐naphthoxy)propane‐1,2‐diol‐3,3‐2H2 (5). Tosylation afforded the primary tosylate (6) which was converted into 3‐(1‐naphthoxy)‐1,2‐epoxypropane‐3,3‐2H2 (7). Reaction of 7 with isopropylamine afforded 1 in 31% overall yield from 4. Reaction of 1‐naphthol‐180 (8) with epichlorohydrin (pyridine) afforded a mixture of 1‐chloro‐3‐(1‐naphthoxy‐180)‐2‐propanol (9) and 1,2‐epoxy‐3‐(1‐naphthoxy‐180)propane (10), which was converted to chlorohydrin 9 with HCl. Reaction of 9 with isopropylamine afforded 2 in 60% overall yield from 1‐naphthol‐180.
[N‐methyl‐11C]‐scopolamine: Synthesis and distribution in rat brain
Authors: Vora Manhar M. , Finn Ronald D. , Boothe Thomas E. , Liskwosky David R. , Potter Lincoln T.
Published: October 2006

The muscarinic antagonist [N‐methyl‐11C]‐scopolamine was synthesized by reductive methylation of norscopolamine with H11CHO and sodium cyanoborohydride, and then purified using preparative high performance liquid chromatography (HPLC). Preliminary in vivo studies in rat suggest the distribution of this compound to parallel with the muscarine receptor population in the brain.
Synthese de L'Acide [Pyridinyl‐2‐(14C‐2,6) Dithio]‐3 Propanoique Reactif de Couplage Covalent
Authors: Noel J. P. , Pichat L.
Published: October 2006

3‐([2,6‐14C]2‐pyridinyldithio) propanoic acid, a disulphide covalent coupling reagent was synthesized in 12 steps from sodium [14C] cyanide. Condensation of sodium [14C] cyanide with 1,3‐dibromopropane gave, after hydrolysis [1,5‐14C] glutaric acid: 4 which was converted into [1,5‐14C] glutarimide : 5 by heating at 280°C with anhydrous ammonia. The imide : 5 was then converted into [2, 6‐14C] 2, 6‐dichloropyridine: by 6 by treatment with phosphorous penta and trichlorides. Chlorine removal from 6 by hydrogen (Roney Nickel) gave [2, 6‐14C] pyridine: 7 which was isolated as the hydrochloride. The latter was tranformed into [2, 6‐14C] pyridine‐N‐oxide :11 by hydrogen peroxide treatment. 11 treated by acetic anhydride (15 hours ‐ 130°C) rearranged into 2‐acetyloxy [2, 6‐14C] pyridine: 12 which was hydrolysed into [2, 6‐14C] 2‐pyridone: 13. Thiation of the latter by P2S5 in xylene gave 2‐mercapto [2, 6‐14C] pyridine: 10 which was then oxidized into [2, 6‐14C] 2‐dipyridinyldisuplphide: 14 the chlorination of which lead to [2, 6‐14C] 2‐pyridinylsulfenyl chloride: 15 which was not isolated. It was condensed with 3‐mercapto propanoic acid to give 1 with an overall yield of 4% based on sodium cyanide ‐ Specific activity was 55 mCi/mMol. The radiochemical purity checked by TLC and HPLC was 98.7%.
Deuteration with Lindlar's catalyst: Effects of various poisons on isotopic purity
Authors: Adlof R. O. , Emken E. A.
Published: October 2006

The Lindlar‐catalysed deuteration of methyl stearolate was studied to determine the effect of various poisons on the rate of reaction and on the isotopic purity of the methyl oleate‐9, 10‐d2 produced. Poisons containing both exchangable and nonexchangable α protons on the heterocyclic ring [quinoline, quinaldine, γ‐collidine, acridine, and pyridine] were used. All poisons yielded methyl oleate‐9, 10‐d2 having 94–97% isotopic purity. Very little over‐reduction of oleate to stearate occurred. Lindlar‐catalysed H‐D exchange involving the poisons was not significant.
Deuterated anabolic drugs. Part 2 synthesis of (R,S)‐3, 4‐bis(4‐hydroxyphenyl)‐[2,2,5,5‐d 4]hexane (HEX‐d4) and (E,E)‐3,4‐bis(4‐hydroxyphenyl)‐[2,5‐d2]hexa‐2,4‐diene (DE‐d2)
Authors: Zomer Gijsbert , Derks Henk J. G. M. , Wynberg Hans
Published: October 2006

Hexestrol‐d4 was synthesized from 1‐hydroxy‐1p‐methoxyphenyl‐[2,2‐d2]propane (7) by reductive coupling. The preparation of 7 involved reduction of p‐methoxy‐[2,2‐d2]propiophenone (2b) obtained by exchange deuteration. Dienestrol‐d2 was synthesized from p‐hydroxy‐[2,2‐d2]propiophenone by pinacol coupling followed by dehydratation of the coupling product using acetic anhydride/acetyl chloride.
Deuteration of verapamil by acid catalyzed exchange
Authors: Nelson Wendel L. , Bartels Michael J.
Published: October 2006

Deuteration of verapamil, 5‐[(3,4‐dimethoxyphenylethyl)methyl‐amino]‐2‐(3,4‐dimethoxyphenyl)‐2‐isopropyvaleronitrile, an important calcium channel antagonist was accomplished by direct exchange in 25% 2H2SO4 in 2H2O. Refluxing for 140 hr incorporated 4–6 atoms of deuterium, which were distributed into both aromatic rings, but primarily in the ring attached through position 5 of the valeronitrile moiety.
Deuterium labelling of the GABA agonist thiomuscimol
Authors: Jacobsen Poul , Krogsgaard‐Larsen Povl
Published: October 2006

Deuterium labelled thiomuscimol (6) was synthesized via catalytic deuteration in strongly basic C2H3O2H‐2H2O (9:1) of 3‐methoxy‐4‐bromo‐5‐(N‐methoxycarbony Iaminomethyl)isothiazole (3). The replacement of bromine by deuterium was accompanied by partial exchange of the side chain methylene protons for deuterium and by complete reesterification of the methoxycarbonyl group. Acid catalyzed deprotection of the reduction product 3‐methoxy‐4‐[2H]‐5‐(N‐[2H]methoxycarbonylamino[2H]methyl)isothiazole (5) gave 6 with only minor loss of deuterium from the ring and side chain.
A potentially general synthesis of high specific activity specifically labelled tritiated peptides: Synthesis of [D‐3‐(2‐naphthyl)‐[2,3‐3H]alanine6]LHRH
Authors: Parnes Howard , Shelton Emma J.
Published: October 2006

High specific activity (43.7 Ci/mmol) D‐3‐(2‐naphthyl)‐[2,3,‐3H] alanine (7) was obtained by reduction of methyl 2‐N‐acetylamino‐3‐(2‐naphthyl) acrylate (5) with carrier free tritium in the presence of (Ph3P)3RhCl followed by enzymatic resolution and hydrolysis. Reductions of 5 and other substrates catalyzed by Pd/C afforded products of low to medium specific activity (0.1–17 Ci/mmol).

A synthetic approach which maximizes the specific activity, guarantees specificity of label, and may be applied toward the preparation of any tritiated (or 14C) peptide is suggested.

The synthesis of the decapeptide [D‐3‐(2‐naphthyl)‐[2,3‐3H]alanine6]LHRH (12) at 45.7 Ci/mmol, using this methodology, is described.
The synthesis of C‐13 labeled vitamin E, [12′‐13C] all‐rac‐α‐tocopherol
Authors: Urano Shiro , Nakano Shun‐Ichiro , Matsuo Mitsuyoshi
Published: October 2006

[12′‐13C]all‐rac‐α‐Tocopherol (1) was synthesized from [2‐13C]acetone. The condensation of 6‐methoxymethoxy‐2,5,7,8‐tetramethyl‐2‐(5‐mercaptothiazolinyl‐4‐methyl‐3‐penten‐1‐yl)chroman (8) with [7‐13C]geranyl bromide (7), which was prepared by the coupling of (6‐benzoyloxy‐4‐methyl‐4‐hexenyl)triphenylphosphonium bromide (5) with [2‐13C]acetone following bromination, afforded [12′‐13C]6‐methoxymethoxy‐2,5,7,8‐tetramethyl‐2‐(3E,7E,9E)‐5‐mercaptothiazolinyl‐(4,8,12‐trimethyl‐3,7,9‐tridecatrien‐1‐yl) chroman (9). After desulfurization and reduction of 9, the reaction product obtained was converted into [12′‐13C]all‐rac‐α‐tocopherol (1) by hydrolysis. The total yield of 1 was 33.7% on the basis of [2‐13C]acetone.
The synthesis of oxygen‐18 enriched phenol and naphthol from 18O2
Authors: Walker T. E. , Goldblatt M.
Published: October 2006

Phenols enriched with oxygen‐18 can be synthesized using an acid exchange reaction in H218O at elevated temperature, however, to obtain highly enriched products very large quantities of water must be used and recycled. Grignard reagents will react readily with oxygen gas with almost no isotopic dilution to produce the 18O enriched alcohol or phenol. Aromatic Grignards do not produce as high a yield as the aliphatic Grignards, however, both provide convenient routes to labeled products. The yield of naphthol from an aryl halide can be improved by the addition of an aliphatic halide (which produces the alcohol as a by product), however, the yield of naphthol from 18O2 gas is not improved by this approach. Either 1‐bromo‐naphthalene or bromobenzene was converted into the Grignard reagent and reacted with oxygen‐18 enriched gas at 0° in a sealed reaction system. The reaction was worked up in the conventional manner and the yields from 18O2 were 34% for [18O] phenol and 23% for 1‐[18O]naphthol.
Preparation of sodium cromoglycate (intalR) labelled with isotopic hydrogen
Authors: Lockley W J S , Wilkinson D J
Published: October 2006

Procedures for the labelling of the anti‐allergic drug, sodium cromoglycate, with both tritium and deuterium are described. Sodium [6,6′,8,8′‐2H] cromoglycate was prepared by acid catalysed exchange with deuterosulphuric acid. The 2‐2H and 2‐3H isotopomers were prepared via borodeuteride and borotritide reductions of an oxo‐precursor. Sodium [3,3′‐3H] cromoglycate was prepared at high specific radioactivity by rhodium(III) chloride catalysed exchange with high atom % abundance tritiated water.
Specific radioactivity determinations of ionic organic compounds of high specific activity by fast atom bombardment and field desorption mass spectrometry
Authors: Lehmann W. D. , Kaspersen F. M.
Published: October 2006

Carbon‐14 and tritium labelled ionic organic compounds such as quaternary ammonium salts, steroid sulphates, bile acid conjugates, and oligopeptides have been analyzed for their label distribution and for their specific radioactivity by fast atom bombardment and field desorption mass spectrometry. No significant differences between the quantitative results with both techniques are found. The minimal specific radioactivities detectable by this approach are about 20 MBq mmol−1 or 10 GBq mmol−1 for compounds labelled with one atom of carbon‐14 or one atom of tritium per molecule, respectively. Specific radioactivity determinations of highly labelled biochemicals are characterized by a precision and an accuracy in the region between 1% and 5%.
Preparation of high purity carbonyl[35S]sulphide
Authors: Kluczewski S. M. , Brown K. A. , Bell J. N. B. , Sandalls F. J. , Jones B. M. R. , Minski M. J.
Published: October 2006

The title compound was synthesised by the reaction between elementary[35s]sulphur and carbon monoxide at 300°C, and purified by passage over Porapak QS. The only detectable S‐impurity in the purified product was CS2 at <0.05% (v/v) of the COS concentration.
Application of the nucleophilic substitution reaction to the synthesis of No‐carrier‐added [18F]fluorobenzene and other 18F‐labeled aryl fluorides
Authors: Shiue C.‐Y. , Watanabe M. , Wolf A. P. , Fowler J. S. , Salvadori P.
Published: October 2006

No‐carrier‐added (NCA) [18F]fluorobenzene was prepared in a multistep synthesis with a radiochemical yield of 20‐30%.

A series of NCA and CA 18F‐labeled aryl fluorides which are important precursors of 18F‐labeled butyrophenone neuroleptics have also been synthesized in radiochemical yields of 30–50%. The direct synthesis of [18F]spiroperidol and [18F]benperidol from the parent compounds and/or nitro and/or chloro compound using the nucleophilic substitution reactions were also investigated.
The preparation of [15N,15N′]‐ and [4,4′‐13C2]‐4,4′‐dichloroazobenzene and [15N, 15N′]‐4‐chloroazobenzene
Authors: Shine Henry J. , Rhee Eun Sook
Published: October 2006

Syntheses of specifically labelled [15N,15N′]‐ and [4,4′‐13C2]‐4,4′‐dichloroazobenzene and [15N, 15N′]‐4‐chloroazobenzene have been accomplished.
Deuterium, tritium, and carbon‐14 labeling of 9‐[ [2‐methoxy‐4‐[ (methylsulfonyl)amino]phenyl] amino]‐N, 5‐dimethyl‐acridinecarboxamide (CI‐921), a new antitumor agent
Authors: Hays Sheryl J. , Huang C. C.
Published: October 2006

CI‐921 2, a potent antitumor agent has been labeled with deuterium and tritium by an exchange reaction employing platinum black as a catalyst. The title compound was carbon‐14 labeled from 2‐chloro‐benzoic‐carboxy‐14C acid to produce the isethionic salt 2d with a specific activity of 26.9 mCi/mmol. The overall radiochemical yield for the carbon‐14 sequence was 22%.
Synthesis of a highly tritiated photoaffinity labelled pheromone analog for the moth antheraea polyphemus
Authors: Prestwich Glenn D. , Golec Frederick A. , Andersen Niels H.
Published: October 2006

The synthesis of the tritiated sex pheromone of the saturniid moth Antheraea polyphemus was accomplished by stereospecific T2 reduction of (E)‐hexadec‐6‐en‐11‐yn‐1‐yl acetate. The [11, 12‐3H2]‐(E, Z)‐6, 11‐hexadecadieny 1 acetate was then converted to the corresponding diazoacetate, a behaviorally active photoaffinity label for the A. polyphemus pheromone binding and receptor proteins. Synthesis of the enyne precursors is also described.
Synthesis, characterization, and in vivo disposition of iodinatable polyethylene glycol derivatives: Differences in vivo as a function of chain length
Authors: Larwood David J. , Szoka Francis C.
Published: October 2006

A series of iodinatable water soluble polyethylene glycol (PEG) derivatives were prepared for use as model hydrophilic drugs. Polyethylene glycol diamine 6000 was coupled to methyl p‐hydroxybenzimidate, and PEG 1900‐ and PEG 5000‐monomethyl ethers were coupled to tyramine and histamine. The derivatives underwent facile iodination with the chloramine‐T reaction and were stable under a wide range of conditions. The larger derivatives showed rapid renal clearance, but the 1900 MW compounds underwent significant clearance via the bile.
The synthesis of deuterium labelled mono‐hydroxy metabolites of phenytoin
Authors: Hoskins John A
Published: October 2006

The synthesis of the 3‐hydroxyphenyl and 4‐hydroxyphenyl metabolites of 5,5‐diphenylhydantoin (Phenytoin) labelled with deuterium in either of the two phenyl rings and 5(4‐hydroxy‐[2H4]phenyl)‐5‐[2H5] phenylhydantion is described.
Probes for narcotic receptor mediated phenomena 8. Tritiation of irreversible mu or delta specific opioid receptor affinity ligands to high specific activity
Authors: Burke Terrence R. , Rice Kenner C. , Jacobson Arthur E. , Simonds William F. , Klee Werner A.
Published: October 2006

Tritiation of the delta‐specific opioid alkylating ligand FIT, 3 and the mu‐specific opioid alkylating ligand BIT, 9 to high specific activity is described. Both compounds were derived from dibrominated amino intermediates (4 and 10, respectively) which were tritiated with tritium gas over Pd/C before conversion of the amine functions to isothiocyanates.
Synthesis of [2‐d]estradiol, [4‐d]estradiol, [2‐t]estradiol and [4‐t]estradiol with high specificity
Authors: Porubek David J. , Namkung Moses J. , Juchau Mont R. , Nelson Sidney D.
Published: October 2006

17‐β‐Estradiol has been labeled in the 2 or 4 position with tritium or deuterium. Both 2‐ and 4‐iodoestradiol were prepared by treatment of estradiol with N‐iodosuccinimide in ethanol followed by chromatographic separation. Reductive dehalogenation of 2‐ and 4‐iodoestradiol with tritium gas gave [2‐t] estradiol and [4‐t] estradiol, respectively, with specific activities of approximately 2 Ci/mmole. Greater than 99% of the radiolabel was incorporated into the target positions as determined by rehalogenation of the radiolabeled compounds. Analysis of the deuterium labeled compounds, [2‐d] estradiol and [4‐d] estradiol, similarly prepared by reduction with deuterium gas, revealed that isotope incorporation was high and specific.
Syntheses of 2‐([14C]methyl)furan and 4‐oxo[5‐14C]‐2‐pentenal
Authors: Ravindranath Vijayalakshmi , Burka Leo T. , Boyd Michael R.
Published: October 2006

A simple one‐step syntheses of 2‐([14C]‐methyl) furan and 4‐oxo‐[5‐14C]‐2‐pentenal have been described. Carbon‐14 labeled 2‐methylfuran was synthesized by treatment of 2‐furyl lithium with 14C‐methyl iodide, and 14C‐acetylacrolein was obtained by peracid oxidation of labeled 2‐methylfuran.
A facile microsynthesis of 14C‐labelled picene
Authors: Beermann Dieter , Petrovic Peter , Seidel Albrecht , Oesch Franz
Published: October 2006

Microscale Wittig olefination of commercially available [7‐14C]‐benzal dehyde of high specific radioactivity with aryl bromomethyl phosphonium salt and subsequent oxidative photocyclisation affords pure 14C‐labelled picene in efficient yield.
Synthesis of 11C‐labelled choline
Authors: Diksic Mirko , Yamamoto Y. Lucas , Feindel William
Published: October 2006

We report the synthesis of 11C‐labelled choline using the reaction of “nocarrier‐added” 11C‐labelled methyliodide and 2‐amino‐(N,N‐dimethyl)‐ethanol. After determining the optimum temperature and duration for the reaction, we achieved a radiochemical yield of about 30% and the radioactivity levels needed for PET studies in humans.
Radiosynthesis of no‐carrier‐added 75,77Br‐brombenperidol
Authors: Moerlein S. M. , Stöcklin G.
Published: October 2006

A three‐step synthesis of the neuroleptic benperidol is presented, and the rapid no‐carrier‐added (n.c.a.) radiobromination of this compound to form brombenperidol (BBP), a radiolabelled dopaminergic receptor‐binding ligand, is described. N.c.a. radiobromination of benperidol using dichloramine‐T in trifluoroacetic acid at elevated temperatures results in bromination totally at the benzimidazolinyl ring of the neuroleptic, leaving the molecular characteristics necessary for receptor binding unaltered. Radiopharmaceutical production results in n.c.a. 75,77Br‐brombenperidol with a corrected radiochemical yield of 30% and a specific activity exceeding 8,000 Ci/mmol.
Synthesis of N‐hydroxymethylpentamethylmelamine (ring 14C), a cytotoxic‐alkylating metabolite of hexamethylmelamine
Authors: Sanders Mark E. , Ames Matthew M.
Published: October 2006

The 14C‐ring labeled carbinolamine N‐hydroxymethylpentamethyl‐melamine, a metabolite of the clinically useful anticancer agent hexamethylmelamine, was prepared in good yield from cyanuric chloride (ring, 2,4,6,‐14C). Amination of cyanuric chloride with dimethylamine gave 2‐chloro‐4,6‐bis(dimethylamino)‐1,3,5‐triazine‐2,4,6‐14C. Further amination with anhydrous methylamine gave pentamethylmelamine‐2,4,6‐14C. Condensation of pentamethylmethyl‐melamine with excess aqueous formaldehyde gave N‐hydroxymethylpentamethylmelamine in 54% overall yield.
Synthesis of N‐[35S]‐sulpho‐2‐amino tricarballylate
Authors: Brown Malcolm R. , Shankar Ravi , Sallis John D.
Published: October 2006

The synthesis of [35S]‐labelled N‐sulpho‐2‐amino tricarballylate (SAT) and methods for its purification and analysis are described. In the first stage of the two‐step synthesis, chloro‐[35S]‐sulphonic acid is reacted with pyridine to yield pyridine‐[35S]‐sulphur trioxide. This agent is then utilized to sulphonate 2‐amino tricarballylic acid yielding the ultimate product [35S]‐SAT, which was required for pharmacokinetic studies.
Two syntheses of 7,8‐dichloro‐1,2,3,4‐tetrahydroisoquinoline‐1‐14C
Authors: Mendelson Wilford L. , Villani Anthony J. , Petka Louis A. , Spainhour Charles B.
Published: October 2006

Two complementary radiosynthetic routes to the potent PNMT inhibitor 7,8‐dichloro‐1,2,3,4‐tetrahydroisoquinoline‐1‐14C(1) from 2,3‐dichlorobenzaldehyde‐formyl‐14C(4) are described. In the Pomeranz‐Fritsch sequence isoquinoline 6 was prepared from Schiff's base 5. Catalytic hydrogenation of 6 (H2/PtO2) furnished 1 in 28% radiochemical yield from 4. In the aluminum chloride fusion sequence, 4 was converted via amino alcohol 7 to chloro amine 8. Treatment of the latter with aluminum chloride/ammonium chloride (fusion, 190°C) yielded labeled 1 in 31% radiochemical yield from 4.
1,3,5‐Trinitroso‐ and 1,3,5‐trinitrohexahydro‐1,3,5‐triazine‐2H6
Authors: Boyer Joseph H. , Kumar G.
Published: October 2006

Perdeuteration of 1,3,5‐trinitrosohexahydro‐1,3,5‐triazine was brought about by treatment with potassium alkoxide in CH3O2H(99.5%). The important high energy compound, 1,3,5‐trinitrohexahydro‐1,3,5‐ triazine (RDX), was obtained in its perdeuterated modification (>99% 2H) by oxidation of the perdeuterated trinitrosamine with a mixture of nitric acid (100%) and hydrogen peroxide (30%).
Synthesis and physico‐chemical properties of (R, S)‐6‐ditrideuteriomethylamino‐4,4‐diphenylheptan‐3‐one hydrochloride (methadone‐d6)
Authors: Gérardy Bruno M. , Poupaert Jacques H. , Vandervorst Daniel , Dumont Pierre , Declerq Jean‐Pierre , Van Meerssche Maurice , Portoghese Philip S.
Published: October 2006

A reaction sequence is described to synthesize (R, S)‐6‐ditrideuteriomethylamino‐4,4‐diphenylheptan‐3‐one hydrochloride ( methadone‐d6.HCl ) in 10.5% overall yield starting from dimethylamine‐d6 hydrochloride. While methadone‐d6.HCl had rather similar physicochemical properties compared to methadone.HCl in the solid phase, a divergent behaviour was observed in solution ( pKa, chromatographic and 13C‐NMR data ). A higher basicity along with a more important hydrophilicity were observed for the d6‐derivative. A 13C‐NMR study showed significant differences in the 13C chemical shifts, which were attributed in part to the intrinsic nature of D itself and in part to a conformational perturbation. The longer duration of antinociceptive action, along with higher t1/2 and clearance, and the depression of the metabolic N‐demethylation process were the only biological properties modified by the deuteration.
synthesis of 10‐[3H]‐5H‐dibenz[b, f] azepine‐5‐carboxamide ([3H]‐carbamazepine)
Authors: Brundish D. E.
Published: October 2006

The title compound has been prepared from a bromo derivative at a specific activity of 27 Ci mmol−1 with radiochemical purity of 98.4% by a selective catalytic reduction with tritium gas. Bromine was replaced without reduction of the stilbene double bond using a poisoned, deactivated catalyst.
Synthesis of 3′‐CTNU radiolabelled with 14C in the alkylating moiety and 3H in the carbamoylating moiety
Authors: Brubaker William F. , Prusoff William H.
Published: October 2006

[6‐3H]3′‐[3‐(2‐Chloroethyl)‐3‐nitrosoureido]‐3′‐deoxythymidine ([3H]3′‐CTNU) radiolabelled with 3H in the carbamoylating moiety has been synthesized in high yield by conversion of tritiated 3′‐amino‐3′‐deoxythymidine([3H]3′‐ATdR) to [6‐3H]3′‐[3‐(2‐chloroethylureido)]‐3′‐deoxythymidine ([3H]3′‐UTdR), followed by nitrosation with N2O3 gas. The title compound radiolabelled with 14C in the alkylating moiety was prepared by conversion of [2‐14C]ethanolamine hydrochloride to [1‐14C]chloroethylamine hydrochloride, followed by reaction with phosgene to yield [1‐14C] chloroethyl isocyanate. This was converted to 3′‐3‐([1‐14C] 2‐chloroethylureido)‐3′‐deoxythymidine([14C]3′‐UTdR), and nitrosated to afford 3′‐[3‐([1‐14C] 2‐chloroethyl) ‐3‐nitrosoureido]‐3′‐deoxythymidine ([14C]3′‐CTNU). HPLC methodology was developed for the purification of intermediate and final products.
Synthesis of 14C‐labeled and 2H‐labeled dibucaine
Authors: Chaudhuri Naba K.
Published: October 2006

A synthesis of dibucaine labeled with 14C in the heterocyclic ring is described. The synthesis was accomplished in five steps starting with isatin and acetic anhydride‐2‐14C as shown in Scheme I. Two deutero analogs, dibucaine‐d2 and dibucaine‐d9, were also synthesized by the reactions shown in Scheme II. Dibucaine‐d9, was synthesized by condensation of 2‐chloro‐N‐[2‐(diethylamino)ethyl]‐4‐quinoline carboxamide with sodium salt of n‐butyl‐d9 alcohol. Dibucaine‐d2 was synthesized by condensation of 2‐chloroquinoline carboxylic acid chloride with N,N‐diethyl dideutero‐ethylenediamine (prepared from chloroacetyl chloride) followed by reaction with sodium n‐butoxide. 14C‐labeled dibucaine was found to undergo considerable radiolysis on storage to give 2‐butoxy‐quinoline‐4‐carboxamide as a major decomposition product.
Synthesis of deuterium‐labeled imipramine using acid‐catalyzed exchange reaction
Authors: Baba S. , Furuta T. , Sasaki Y. , Kasuya Y.
Published: October 2006

Synthesis of three forms of selectively deuterated imipramine with high isotopic purity using acid catalyzed hydrogen‐deuterium exchange reaction is described. Deuterated imipramine labeled at the positions of 2,4,6 and 8 [IP‐d4(I)] was prepared directly by heating imipramine in 10% DCl‐D2O at 80° for 8hr. Imipramine labeled at all of the eight aromatic positions (IP‐d8) was synthesized from iminodibenzyl‐1,2,3,4,6,7,8,9‐d8 which was prepared by treating iminodibenzyl (IDB) in 37% DCl‐D2O at 160° for 24hr. And imipramine labeled at the positions of 1,3,7 and 9 [IP‐d4(II)] was obtained by “back‐exchange” of IP‐d8 under the protio condition according to the exchange procedure of IP‐d4(I).
The syntheses of 1‐[11C]‐D‐glucose and related compounds for the measurement of brain glucose metabolism
Authors: Shiue Chyng‐Yann , Wolf Alfred P.
Published: October 2006

A new synthesis of 1‐[11C]‐D‐glucose (3) and related compounds from H11CN is described. Reaction of D‐arabinose (1) with Na11CN at pH 8 gives 1‐[11C]‐aldononitriles (2). Reduction of 2 with Raney alloy in 30% formic acid gives 1‐[11C]‐D‐glucose (3) and 1‐[11C]‐D‐mannose (4) in radiochemical yields of ∼ 40–50% (EOB) in a synthesis time of 50 min from EOB. The yield and ratio of 3 and 4 is pH dependent. Compounds 3 and 4 are separated by HPLC. The radiochemical yield of 3 is ∼ 15% (EOB) and the total synthesis time (including HPLC purification) is 70 min from EOB. The same method has also been applied to synthesize 1‐[11C]‐D‐galactose (6) with radiochemical yields of ∼ 30% (EOB) in a synthesis time of 70 min from EOB. The advantages and disadvantages of this synthetic method are discussed.
Synthesis of 14C‐labelled 1‐(3,5‐bis‐trifluoromethyl)‐phenyl‐4‐methyl thiosemicarbazide, C 2696‐GO
Authors: Maller R. K. , Nagarajan K. , Zoebeli H.
Published: October 2006

For pharmacokinetic and metabolism studies in experimental animals C 2696‐Go was labelled initially with 14C on the thiocarbonyl carbon of the thiosemicarbazide moiety of the molecule, having a specific activity of 3.14 μCi/mg, in a radiochemical yield of 43%, based on the starting potassium [14C]thiocyanate.

C 2696‐Go alternatively labelled with 14C on one of the trifluoromethyl groups, having a specific activity of 3.6 μCi/mg was also synthesized in an overall radiochemical yield of 5.1%, starting from Ba[14C]O3.
Synthesis of [5,6‐13C2, 1‐14C]olivetolic acid, methyl [1′‐13C]olivetolate and [5,6‐13C2, 1‐14C]cannabigerolic acid
Authors: Porwoll Joseph P. , Leete Edward
Published: October 2006

Potential advanced intermediates in the biosynthesis of Δ9‐tetrahydrocannabinol have been synthesized labeled with two contiguous 13C atoms and 14C. Methyl [5,6‐13C2, 1‐14C]olivetolate was prepared from lithium [13C2]acetylide and dimethyl [2‐14C]malonate. Reaction with geranyl bromide afforded methyl [5,6‐13C2, 1‐14C]cannabigerolate, and hydrolysis of these methyl esters with lithium propyl mercaptide yielded the corresponding labeled acids. The 13C‐13C couplings observable in the 13C NMR spectra of these 13C‐enriched compounds and their synthetic precursors are recorded. Methyl [1′‐14C]olivetolate was prepared from 13CO2 to confirm assignments of the 13C chemical shifts in the pentyl side chain of these compounds.
Microscale synthesis of volatile, 14C‐labelled acid chlorides
Authors: Parnes Howard , De Keczer Steve
Published: October 2006

A method for the microscale (one mmole) synthesis of volatile, 14C‐labelled acid chlorides from Ba14CO3 using vacuum line techniques is described. By a judicious choice of reagents, desired intermediates and products may be isolated in high yield by simple vacuum transfer techniques without fractionation.
Synthesis of [4‐3H]‐2‐pyrrolidinone, [4‐3H]‐N‐methyl‐2‐pyrrolidinone and N‐[14C‐methyl]‐2‐pyrrolidinone
Authors: Wells David A. , Chaney James E. , Digenis George A.
Published: October 2006

An efficient synthesis of 2‐pyrrolidinone and N‐methyl‐2‐pyrrolidinone was developed in which the compounds can be labeled with tritium at either the 3‐ and 4‐positions or the 4‐position of the lactam ring. Cyclization of [2,3‐3H]‐γ‐aminobutyric acid (GABA) yielded [3,4‐3H]‐2‐pyrrolidinone and cyclization of [3‐3H]‐GABA, prepared by acid‐catalyzed exchange of tritium from [2,3‐3H]‐GABA, yielded [4‐3H]‐2‐pyrrolidinone was synthesized by methylation of [3,4‐3H]‐2‐pyrrolidinone using phase transfer catalysis, followed by basecatalyzed tritium exchange. N‐[14C‐Methyl]‐2‐pyrrolidinone was prepared from [14C] methyl iodide and 2‐pyrrolidinone, also using phase transfer catalysis.
Synthesis and 3H NMR of 3H‐alaproclate of high specific activity
Authors: Bengtsson Stefan , Gawell Lars , Högberg Thomas , Sahlberg Christer
Published: October 2006

The antidepressant alaproclate (1) is a selective inhibitor of neuronal serotonin reuptake with low affinity for other receptor sites. 3H‐Alaproclate (3, 2‐([2,5‐3H2]‐4‐chlorophenyl)‐2‐methyl‐2‐propyl 2‐aminopropanoate) with high specific activity (38 Ci/mmol) was prepared by hydrogenolysis of its 2,5‐dibromo analogue 2 with tritium gas. The compound 2 was prepared in a seven step synthesis from 4‐chlorotoluene. The position of the tritium incorporation was verified by 3H NMR.
The preparation of carbon‐14 labeled avermectin B1a
Authors: Ku C. C. , Hwang S. C. , Kaplan L. , Nallin M. K. , Jacob T. A.
Published: October 2006

Carbon‐14 labeled avermectin B1a was synthesized by a fermentation process using sodium [1‐14C]propionate as the precursor, then isolated and purified by preparative HPLC. The total amount of purified product obtained in this preparation was 225 mg with a specific activity of 16.4 μCi/mg. The radiopurity was 99+% by TLC and HPLC analyses. The labeled positions were determined by carbon‐13 NMR analysis of [13C]propionate. The labeled atoms were determined to be C‐3, C‐7, C‐11, C‐13 and C‐23. However, EI/MS indicated this product was a mixture of five single carbon‐13 labeled compounds. The overall radiochemical yeild of [14C]avermectin B1a biosynthesis was estimated to be 0.69%.
Gas‐liquid chromatographic determination of relative amounts of 2‐deoxy‐2‐flouro‐D‐glucose and 2‐deoxy‐2‐fluoro‐D‐mannose synthesized from various methods
Authors: Shiue Chyng‐Yann , Fowler Joanna S. , Wolf Alfred P. , Alexoff David , Macgregor Robert R.
Published: October 2006

A column (6 ft × 1/8 in) containing 4% SE‐30 + 6% OV‐210 on Chromosorb W‐HP 80/100 mesh was employed to determine the relative amounts of 2‐deoxy‐2‐fluoro‐D‐glucose (2‐FDG) and 2‐deoxy‐2‐fluoro‐D‐mannose (2‐FPM) synthesized using various methods. The 2‐FDG synthesized from published methods contains 4–56% of 2‐FDM.
Synthesis OF 3‐[14C]‐(p‐chlorophenylthio)‐2‐aminopropane hydrochloride (C 2998‐Go)
Authors: Maller R. K. , Nagarajan K. , Nair M. D.
Published: October 2006

For pharmacokinetic and metabolism studies in animals and humans, C 2998‐Go, an antidepressant was labelled with carbon‐14 on the thiomethylene carbon. The radiolabelled compound having a specific activity of 1.82μCi/mg was obtained in an overall yield of 13.6% using [14C]paraformaldehyde and with a radiochemical purity >98%.
Synthesis of |21‐14C|‐3β‐hydroxy‐5β‐pregnan‐20‐one and |21‐14C|‐5β‐cholestan‐3β‐ol
Authors: Garraffo H. M. , Deluca M. E. , Seldes A. M. , Gros E. G.
Published: October 2006

|21‐14C|‐3β‐Hydroxy‐5β‐pregnan‐20‐one was synthesised from 3β‐acetoxy‐5β‐androstan‐17β‐carboxylic acid chloride and |14C2|dimethyl‐cadmium. Reaction of the labelled product with isohexyl bromide yielded, after dehydration and catalytic hydrogenation, |21‐14C|‐5β‐cholestan‐3β‐ol (|21‐14C|‐coprostanol).
Synthesis of 14C‐labelled etintidine hydrochloride
Authors: Stefanick Stephen M. , Kasulanis Charles F. , Levine Seymour D. , Fabian Arthur C.
Published: October 2006

Two 14C preparations of the H2‐antagonist etintidine hydrochloride are reported. In one, the label is introduced by reacting [1‐14C] propargylamine with the appropriate isothiourea, followed by hydrochloride formation. This afforded a material of 95% radiochemical purity whose specific activity was 1.5 mCi/mmol.

To obtain material labelled in an alternate position, uniformly labelled 14C‐cysteamine hydrochloride was reacted with 4‐methyl‐5‐hydroxymethyl Imldazole hydrochloride to produce 4‐methyl‐5‐[(2‐aminoethyl)thiomethyl]lmidazole. This was converted in three additional steps to etintidine hydrochlorlde yielding material of 96% radlochemlcal purity and specific activity of 9.0 mC1 /mnol.
Efficient syntheses of deuterium labeled epinines
Authors: Sinhababu Achintya K. , Borchardt Ronad T.
Published: October 2006

Syntheses of N‐methyl‐2‐(3,4‐dihydroxyphenyl)ethylamine hydrochlorides (epinines) labeled with deuterium in the ring, in the N‐methyl group and both in the ring and N‐methyl group are described. The N‐trideuteromethyl group was generated by the LiAlD4 reduction of the corresponding carbamate while the ring deuterated epinines were produced by the DCl catalyzed exchange in D2O of the corresponding ring unlabeled epinines.
Synthesis of 16‐iodo‐[carboxyl‐14C]hexadecanoic acid
Authors: le Bars D. , Apparu M. , Léo P. M. , Vidal M. , Luu‐Duc C.
Published: October 2006

Iodo‐hexadecanoic acid labelled with carbon 14 in the carboxyl group was obtained with good yield in three steps from [14C] NaCN using bromopenta decyl tetrahydropyranyl ether 2. Specific radioactivity: 0.0166 mCi/mg; 6.34 mCi/mmol. Radiochemical yield: 69.6 % of the theoretical amount.
Tritium labelled hyaluronic acid derivative
Authors: Orlando P. , de Sanctis G. , Giordano C. , Valle G. , la Bua R. , Ghidoni R.
Published: October 2006

High molecular weight hyaluronic acid derivative was prepared in a radioactive form, labelled with tritium.

The mucopolysaccharide was oxidized under mild conditions by sodium periodate. After purification the oxidation product was reduced with [3H]NaBH4. The tritium labelled hyaluronic acid derivative was obtained with a high specific radioactivity (0.15 mCi/mg) and was found to have similar physical and chemical characteristics (high molecular weight, infrared spectrum and electrophoretical behaviour) to the parent compound. The radiochemical purity of labelled hyaluronic acid derivative was found to be greater than 95%.
Mecanistic study on exchange between labeled cyanide and nitriles
Authors: Hussain Munir , Chaney James E. , Digenis George A. , Layton W. John
Published: October 2006

The potential of a clean, rapid exchange between the nitrile function of mandelonitrile and cyanide was examined for the preparation of labeled mandelonitrile which could be subsequently rapidly reduced with borane to labeled phenylethanolamine (PEOH). The mandelonitrile exchange (CN‐CN) was studied using [13C]‐NaCN with crown ethers in THF, monitoring the results with 13C‐NMR. A large increase in the intensity of the signal due to [13C]‐nitrile was observed. The exchange was also carried out using [14C]‐PEOH. The chemical Yield for the reduction of [14C]‐mandelonitrile to [14C]‐PEOH was 60% and the overall radiochemical yield of the cyanide‐exchange and borane reduction (based on [14C]‐NaCN used) was 20%. Mechanisms are proposed which were found to be consistent with results of cyanide exchange of appropriately selected nitriles.
Synthese de L'Acide (Propyl‐1‐13C)‐2 Pentanoique‐3‐13C (acide valproïque)
Authors: Servens C. , Filliatre C. , Sion R.
Published: October 2006

A method was developped for the synthesis of 2‐(propyl‐1‐13C) pentanoic‐3‐13C acid on a scale of ten grams and with an isotopic purity of 98,9%.