bluuebunny/crossref_metadata_2025 huggingface dataset:
Tritium labeling of simple 7‐membered ring compounds
Authors: Hiltunen J.  , Peng C. T.  , Yang Z. C.
Published: October 2006

Seven‐membered ring compounds, from cylcoheptane to complex ring structures containing heteroatoms, substituents and fused phenyl rings, were labeled with tritium, using activated and adsorbed tritium. The 7‐membered ring structures are generally stable towards reactions with tritium, which allows compounds like 1‐benzosuberone, 1‐aza‐2‐methoxy‐1‐cycloheptene, iminostilbene and clozapine to be labeled to reasonably high specific activities. The best method varies greatly from compound to compound. By optimizing the labeling conditions and use of efficient support exceptionally good results can be obtained. The Pd‐on‐alumina support gives consistently higher specific activity and less radioimpurity than other supports. Even molecules containing carbon‐halogen bond and hydrogen bound to nitrogen can usually be labeled with tritium at stable positions and without dehalogenation.
Synthesis of carbon‐14 and tritium labeled methylprednisolone suleptanate
Authors: Stolle Wayne T , Runge Thomas A. , Hsi Richard S. P.
Published: October 2006

Methylprednisolone suleptanate was initially labeled with tritium in the A‐ring of the steroid portion of the molecule, and with carbon‐14 at both carboxylic carbons of the suberic acid portion of the side chain. However these labels proved to lack total metabolic stability after administration to rats. Subsequently a second pair of labeled methylprednisolone suleptanates was synthesized, with tritium at C‐7 in the B‐ring of the steroid and carbon‐14 exclusively at the carboxamide carbon in the side chain. These labeled compounds showed excellent metabolic stability of both the tritium and carbon‐14 labels, and should be well suited for conducting drug disposition studies.
Preparation of deuterated naphthalenes, anilines, m‐toluidines, and anisoles by reductive dehalogenation of the corresponding halogenated derivatives with raney Cu‐Al alloy in an alkaline deuterium oxide solution
Authors: Tashiro Masashi , Tsuzuki Hirohisa , Tsukinoki Takehito , Mataka Shuntaro , Nakayama Kouji , Yonemitsu Tadashi
Published: October 2006

Four deuterated naphthalenes, ten deuterated anilines, three deuterated m‐toluidines, and five deuterated anisoles were prepared in high isotopic purities from the corresponding halo‐substituted derivatives by the reductive dehalogenation with Raney Cu‐Al alloy in an alkaline deuterium oxide solution.
Synthesis of 3H‐labeled sympathomimetic amines for neuronal mapping
Authors: Van Dort Marcian E. , Gildersleeve David L. , Wieland Donald M.
Published: October 2006

The synthesis of two tritium labeled sympathomimetic amines, (R)‐(‐)‐phenylephrine and (1R,2S)‐(‐)‐meta‐hydroxyephedrine, is described. The tritium label was introduced into the aromatic ring in the final step by catalytic reductive dehalogenation of the corresponding iodinated precursor. (1R,2S)‐(‐)‐meta‐hydroxyephedrine was synthesized in four steps from commercially available metaraminol. A novel HPLC purification method provided the labeled compounds in a medium ready for direct animal evaluation. Chemical and radiochemical purity was ≥98%; specific activity was ≥ 22 Ci/mmol.
A rapid and efficient synthesis of 2‐deoxy‐2‐[18F]fluoroacetamido‐D‐mannopyranose and ‐D‐galactopyranose
Authors: Tada Masao , Oikawa Atsushi , Iwata Ren , Sato Kazunori , Kubota Kazuo , Fujiwara Takehiko , Sugiyama Hiroshi , Abe Yoshinao , Sato Tachio , Matsuzawa Taiju , Takahashi Hiromu , Wakui Akira , Ido Tatsuo
Published: October 2006

Rapid and efficient syntheses of 2‐deoxy‐2‐[18F]fluoroacetamido‐D‐mannopyranose (1) and ‐D‐galactopyranose (2), respectively, starting from [18F]fluoride and ethyl bromoacetate are described. [18F]Fluoride was produced by the 18O (p, n) 18F nuclear reaction using the cyclotron. The total times required for synthesis of (1) and (2) are ca. 80 min. The radiochemical yield and purity of (1) are an 18% and ≥98%, respectively. Compound (2) is also synthesized with the same radiochemical yield and purity.
Radiolabeling of proteins with radioisotopes of copper using p‐carboxyalkylphenylglyoxal bis‐(4N‐methylthiosemicarbazone) (TSC) bifunctional chelates
Authors: McPherson D. W. , Umbricht G. , Knapp F. F.
Published: October 2006

A series of p‐carboxyalkylphenylglyoxal and p‐carboxyalkyl‐1,2‐diketo‐bis‐(N4‐methylthiosemicarbazone) bifunctional ligands (TSC) have been prepared and evaluated for use in binding radioisotopes of copper to antibodies. We have developed an improved synthesis of the requisite α‐ketoaldehyde and 1,2‐diketone substrates used for derivatization to the bis‐TSC bifunctional chelates. This approach utilizes a modified Kornblum method and provides a simple alternative to the usual method for fabrication of the 1,2‐bis‐TSC ligands, which avoids the use of highly toxic selenium dioxide for oxidation of substituted acetophenones to 1,2 dicarbonyl compounds. The overall yields of the bis‐TSC chelates using this procedure were 8‐60%. The effects of the alkyl chain length and substitution on the C‐2 position on p‐carboxyalkylphenyl‐1,2‐diketo bis‐TSC bifunctional chelate for attaching radioisotopes of copper to proteins were studied. Following complexing copper‐64 or copper‐67 to the bis‐TSC chelate, the acid moiety of the TSC chelate was activated as the tetrafluorophenyl ester. The copper‐labeled activated TSC chelate was attached to bovine serum albumin under mild conditions in 3% to 40% yield. These studies have demonstrated that the shorter chain analogues of the TSC chelates from the 1,2‐diketones give the highest radiolabeling yields.
Preparation of enantiomerically‐active deuterium‐labelled ibuprofen
Authors: Chen Ching‐Shih , Copeland Debra , Harriman Shawn , Liu Yeuk‐Cheun
Published: October 2006

The chemoenzymatic preparation of optically‐active [3,3,3‐2H3]‐ibuprofen and [2‐2H]‐ibuprofen are described.
Synthesis of 2,2‐dimethyl‐13C2‐propionitrile‐1‐13C and its conversion to triply carbon‐132labeled dowco 429 insecticide
Authors: Roth G. A. , McClymont E. L.
Published: October 2006

A convenient synthesis of triply carbon‐13 labeled 2,2‐dimethyl‐13C2‐propionitrile‐1‐13C is described. The synthetic sequence begins with commercially available propionic acid‐1‐13C and methyl iodide‐13C with the application of a sequential dianion alkylation. The 2,2‐dimethyl‐13C2‐propionitrile‐1‐13C was carried on to triply labeled DOWCO 429 insecticide for use in residue and metabolism studies.
Synthesis of (3R)‐3‐(4‐fluorophenylsulfonamido)‐1, 2, 3, 4‐tetrahydro‐9‐[4‐3H]carbazolepropanoic acid
Authors: Pleiß Ulrich , Radtke Martin , Schmitt Peter
Published: October 2006

(3R)‐3‐(4‐Fluorophenylsulfonamido)‐1, 2, 3, 4‐tetrahydro‐9‐[4‐3H]carbazolepropanoic acid ([3H]BAY u 3405) (5) was synthesized by catalytic reduction of (3R)‐3‐(4‐fluorophenylsulfon‐amido)‐4‐oxo‐1, 2, 3, 4‐tetrahydro‐9‐carbazolepropanoic acid (4) with tritium. The precursor (4) was prepared by esterification and following oxidation of BAY u 3405 with 2, 3‐dichloro‐5, 6‐dicyano‐p‐benzoquinone. 3H NMR analysis of the final product showed the formation of [4α‐3H]BAY u 3405 and [4ß‐3H]BAY u 3405 in a ratio of 1: 1.
An improved synthesis of dideuterated thioridazine with the label in the piperidine ring
Authors: Mohammad T. , Hawes E. M. , McKay G. , Midha K. K.
Published: October 2006

2‐(2‐Hydroxyethyl)‐1‐methyl [6,6‐2H2]piperidine was obtained by a new route from 2‐(2‐hydroxyethyl)‐piperidine. This enabled dideuterated (±)‐thioridazine to be obtained by an improved approach. The key steps involved ruthenium tetroxide oxidation of the N, O‐diacetylated starting material and subsequent lithium aluminum deuteride reduction of O‐acetylated 2‐(2‐hydroxyethyl)‐6‐pieridinone.
Isolation and characterisation of high molecular weight [3H]hyaluronic acid
Authors: Chabreček P. , Šoltés L. , Kállay Z. , Fügedi A.
Published: October 2006

A high‐performance gel permeation chromatographic separation method was developed for the isolation and characterisation of high molecular weight [3H]hyaluronic acid. The molecular characteristics of the labelled sample were MW=3.92x105 Da, MW/Mn=1.55.
Myocardial imaging agents: Synthesis, characterization and evaluation of [(Z) and (Z,E)‐(1‐[82br]bromo‐1‐penten‐5‐yl)]triphenylphosphonium cations
Authors: Srivastava P. C. , Knapp F. F. , Callahan A. P. , Goldstein B. M.
Published: October 2006

The phosphonium compounds, [(Z) and (Z/E)‐(1‐bromo‐1‐penten‐5‐yl)]triphenylphosphonium iodides (yield, 65–70%) and the corresponding bromine‐82‐labeled analogues have been prepared as potential myocardial imaging agents. The 2/1 isomer composition of the Z/E mixture has been confirmed by single crystal X‐ray analysis. The radiobrominated (Z)‐isomer and (Z/E)‐mixture both show high heart uptake and high heart/blood ratios in rats. These data suggest that the bromine‐75 and bromine‐76‐labeled agents could be good candidates for myocardial imaging using positron emission computed tomography.
High‐yield nitration of benzene in the synthesis of 15N‐labelled nitrobenzene, acetanilide, and diphenylamine
Authors: Konior Raymond J. , Yang Ling , Walter Robert I.
Published: October 2006

Labelled H15NO3 was used as the least‐cost source of nitrogen label to prepare nitrobenzene by reaction of acetyl nitrate with excess benzene. This labelled product was subsequently converted to acetanilide‐15N and diphenylamine‐15N.
A simple and high‐yield synthesis of (S)‐BZM, (R)‐BZM AND (S)‐IBZM for the preparation of (S)‐123I‐IBZM
Authors: Bobeldijk M. , Verhoeff N. P. L. G. , Vekemans J. A. J. M. , Buck H. M. , Van Doremalen P. A. P. M. , Van Hoof J. J. , Janssen A. G. M.
Published: October 2006

(S)‐2‐Hydroxy‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide ((S)‐BZM; (S)‐5a), the precursor of (S)‐2‐hydroxy‐3‐123I‐iodo‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide ((S)‐123I‐IBZM) was synthesized via a simple method and in high yield starting from 2,6‐dimethoxybenzoic acid (1a). N‐Hydroxysuccinimide/dicyclohexyl‐carbodiimide (DCC) was used as activating system in the reaction of 1a with (S)‐2‐aminomethyl‐1‐ethylpyrrolidine (3a).
Synthesis of N‐(α,α,α‐tri[18F]fluoro‐m‐tolyl)piperazine. A potent serotonin agonist
Authors: Angelini G. , Speranza M. , Wolf A. P. , Shiue C.‐Y.
Published: October 2006

N‐(α,α,α‐tri[18F]fluoro‐m‐tolyl)piperazine (6), a serotonin agonist, was synthesized from 3‐nitro‐α,α,α‐trichlorotoluene (1) and H[18F] + Sb2O3 in four steps in 27% overall radiochemical yield in a synthesis time of ˜ 3 hours.
Synthesis of optically pure 13C‐labelled propionate from alanine by asymmetric hydrolysis using porcine kidney acylase
Authors: Iida Katsumi , Kajiwara Masahiro
Published: October 2006

Sodium (R)‐[2‐2H,3‐13C]propionate, sodium (S)‐[2‐2H,3‐13C] propionate, sodium (R)‐[3‐13C]‐2‐fluoropropionate, and sodium (S)‐[3‐13C]‐2‐fluoropropionate were synthesized from D[(S)]‐[3‐13C]alanine and L[(R)]‐[3‐13C]alanine, which were obtained by asymmetric hydrolysis using acylase from porcine kidney.
The synthesis of o‐ and p‐[18F]fluorobenzyl bromides and their application to the prepatation of labeled neuroleptics
Authors: Hatano Kentaro , Ido Tatsuo , Iwata Ren
Published: October 2006

The syntheses of o‐ and p‐ [18F]fluorobenzyl bromides as labeled synthons were described. They were obtained from nitrobenzaldehyde via a three step synthesis that exhibited good yield. The preparation of [18F]fluororinated analog of a benzamide neuroleptic, cis‐N‐[(2RS, 3RS)‐1‐[18F]fluorobenzyl‐2‐methylpyrrolidin‐3‐yl] ‐5‐chloro‐2‐methoxy‐4‐methylaminobenzamide, via N‐benzylation with the synthons was also mentioned.
Preparation of deuteriated succinic acids
Authors: Tashiro Masashi , Tsuzuki Hirohisa , Isobe Shin‐Ichiro , Goto Hideyuki , Ogasahara Shoji , Mataka Shuntaro , Yonemitsu Tadashi
Published: October 2006

Succinic [2,3‐2H2]‐ and [2,2,3,3‐2H4]‐acids were prepared from maleic anhydride and dimethyl fumarate, and acetylene dicarboxylic acid and its dimethyl ester by treatment with CuAl and Ni‐Al alloys in 10% NaOD‐D2O in 95% to 100% isotopic purity. The succinic 2H4 acid having high isotopic purity was also obtained on the hydrolysis of 1,2‐ethanedinitrile with alkaline deuterium oxide. Based on the 1H{2H} spectra analysis of N‐(o‐biphenyl)[2,3‐2H2]succinimide, it was elucidated that the Raney alloy reduction with alkaline deuterium oxide proceeds stepwise.
Synthesis of tritium‐labeled (+)loxistatin (E‐64d)
Authors: Huang Zhenya , McGowan Eleanor B. , Detwiler Thomas C.
Published: October 2006

The enantioselective synthesis of tritium‐labeled (+)loxistatin is described. N‐Boc‐[U‐3H]L‐leucine was the starting material for the threestep synthesis. Boc‐leucine was amidated with isoamylamine. The Bocgroup was removed with 4N HCl in dioxane. Transesterification with ethyl p‐nitrophenyl‐L‐trans‐epoxysuccinate led to (+)loxistatin with a specific radioactivity of 4.4 mCi/mmole and a radiochemical purity of > 97%.
A facile and regiospecific tritiation of sphingosine: Synthesis of (2S,3R,4E)‐2‐amino‐4‐octadecene‐1,3‐diol‐1‐3H
Authors: Toyokuni Tatsushi , Nisar Mohammad , Dean Barbara , Hakomori Sen‐Itiroh
Published: October 2006

An easy technique for introduction of tritium into the 1‐position of sphingosine was developed, employing regiospecific oxidation of the primary hydroxy group followed by reduction with NaB3H4. An improved preparation of N,N‐dimethylsphingosine and its quaternization are also described.
Radiolabelling by tritium and [125I]iodine of an angiotensin II related Peptide
Authors: Pham P. , Ramombordes C. , Perret C. , Ronco P. , Budisavljevic M. , Verroust P. , Beaucourt J. P.
Published: October 2006

We describe the 3H‐ and 125I‐ labelling of Glu‐Gly‐Val‐Tyr‐Val‐His‐Pro‐Val, (hIIA), an octapeptide encoded by an RNA strand complementary to the human angiotensin II (AII) mRNA.

The labelling of this peptide with 125I was performed by two ways : 1/ Mono‐iodination of the Tyr residue, using Na125I in the presence of Chloramine T; 2/ Coupling of the [125I]Bolton‐Hunter reagent to the terminal amine group of the octapeptide.

The synthesis of the tritiated (3,5‐3H2‐Tyr4)octapeptide was achieved by a two step synthesis : di‐iodination of the peptide followed by its catalytic dehalogenation in the presence of tritium gas.

The compounds obtained inhibited the binding of AII to its receptors or antibodies but showed no direct binding to these proteins, suggesting no competition between AII and hIIA for these protein binding sites.
The synthesis of the carbonyl‐14C analog of zatosetron maleate, a potent, long‐acting, orally effective 5‐HT3 receptor antagonist
Authors: O'Bannon Douglas D. , Wheeler William J.
Published: October 2006

Endo‐5‐chloro‐2,3‐dihydro‐2,2‐dimethyl‐N‐(8‐methyl‐8 ‐azabicyclo‐[3.2.1.]‐oct‐3‐yl‐7‐benzofurancarboxamide‐[carbonyl‐14C] (Z)‐2‐butenedioate (zatosetron‐[14C] maleate, 1), has been prepared from 5‐chloro‐7‐bromo‐2,3‐dihydro‐2,2‐dimethylbenzofuran (5) in four radiochemical steps with the reaction of 5 with K14CN/CuCN as the key step. The synthesis of 5 from 2‐bromo‐4‐chlorophenol is also outlined.
Synthesis of carbon‐14 labelled cis‐2‐amino‐1,9‐dihydro‐9‐[4‐(hydroxy‐methyl)‐2‐cyclopenten‐1‐YL]‐6H‐purine‐6‐one; [8‐14C]carbovir: A promising anti‐aids drug
Authors: Gopinathan M. B. , Kepler J. A.
Published: October 2006

The synthesis of the title compound (3) is described. Treatment of a solution of triethyl [14C]orthoformate in dry chloroform with cis‐[4‐(2,5‐diamino‐6‐chloro‐4‐pyrimidinyl)‐amino]‐2‐cyclopentenyl carbinol (1) afforded crude 2. Hydrolysis of crude 2 with 2 N sodium hydroxide gave 3 in 34% overall radiochemical yield with specific activity of 19.6 mCi/mmol.
Synthesis of [14CO]ellagic acid
Authors: Zeng Wenguang , Heur Young‐Hun , Kinstle Thomas H. , Stoner Gary D.
Published: October 2006

[14CO]Ellagic acid with a chemical purity of 98.9% and radiochemical purity of 99.9% was synthesized with an overall yield of 16% (both chemically and radiochemically). Reaction of 14CO2 with lithiated 3,4,5‐trimethoxybenzene and demethylation of the resulting 3,4,5‐trimethoxybenzoic acid was followed by esterification and coupling of methyl gallate into ellagic acid. Two efficient coupling methods were employed: direct aeration and aeration of methyl gallate in the presence of the phenolic oxidase, tyrosinase. The latter method produced the highest yield and purity. This preparation produced [14CO]ellagic acid with a specific activity of 20 mCi/mmol. The yields of labeled 3,4,5‐trimethoxybenzoic acid and ellagic acid based on Ba14CO3 were 65% and 16%, respectively.
Asymmetric synthesis of (2S)‐and (2R)‐4‐(3‐t‐butylamino‐2‐hydroxypropoxy)‐benzimidazol‐2‐[11C]‐one ((S)‐and (R)‐[11C]‐CGP 12177) from optically active precursors
Authors: Hammadi Akli , Crouzel Christian
Published: October 2006

Enantiomers of CGP 12177 ((2S)‐and (2R)‐4‐(3‐t‐butylamino‐2‐hydroxypropoxy)‐benzimidazol‐2‐one), a potent adrenergic β‐receptor antagonist were synthesized and labelled with 11C for Positron Emission Tomography studies of β‐receptors in heart. The synthesis was accomplished from (2S)‐and (2R)‐3‐tosyloxy‐1,2‐propanediol acetonide. Enantiomeric excess was greather than 95% for each of the prepared enantiomers. (S)‐ and (R)‐[11C]‐CGP 12177 were obtained with a specific radioactivity of 29.6‐44.4 GBq/μmol.
Synthesis of 2H‐, 3H‐ and 14C‐labelled CP‐45,634 (sorbinil)
Authors: Howard Harry R. , Evans Michael , Sarges Reinhard
Published: October 2006

The syntheses of 3H‐ and 14C‐label led S‐(+)‐6‐fluoro‐2,3‐dihydrospiro‐[4H‐1‐benzopyran‐4,4′‐imidazolidin]‐2′,5′‐dione (sorbinil, CP‐45,634), an aldose reductase inhibitor with potential utility in the treatment of chronic diabetic complications, are described. Tritiated sorbinil was prepared by a reductive dehalogenation of the 8‐chloro substituted analog with 3H2. 14C‐labelled CP‐45,634 was prepared using a Bucherer‐Bergs synthesis of the racemic hydanto in beginning with 2,3‐dihydro‐6‐fluoro‐4H‐1‐benzopyran‐4‐one and 14C‐potassium cyanide, followed by brucine resolution to isolate the pharmacologically active S‐(+)‐enantiomer.
Synthesis of [1,1′ ‐13C2]‐L‐cystine
Authors: Uchida Kenichi , Kainosho Masatsune
Published: October 2006

An improved synthesis of [1,1′‐13C2]‐L‐cystine which includes the optical resolution of the labeled N‐acetyl‐S‐benzyl‐DL‐cysteine by Aspergillus acylase into S‐benzyl‐L‐cysteine is described.
Synthesis of 14 (R,S)‐[18F]fluoro‐6‐thia‐heptadecanoic acid (FTHA)
Authors: Degrado Timothy R.
Published: October 2006

No‐carrier‐added (n.c.a) 14(R,S)‐[18F]fluoro‐6‐thia‐heptadecanoic acid (FTHA) has been synthesized for evaluation as a PET tracer for myocardial long chain fatty acid utilization. The n.c.a. nucleophilic radiofluorination of benzyl 14(R,S)‐tosyloxy‐6‐thia‐heptadecanoate in acetonitrile utilized (cryptate 2.2.2/K)2CO3 for anion activation. The resulting [18F]fluoro‐ester was quantitatively hydrolyzed with addition of aqueous KOH and the product purified by reversed phase HPLC. The radiochemical yield of purified FTHA was 35–65% (n=5) with a synthesis time of 50 min. Radiochemical purity was >99%.
Synthesis of 14‐[2H]arteether, an experimental antmalarial drug
Authors: Hu Yulin , Ziffer Herman
Published: October 2006

A reaction sequence employing a fungus mediated oxidation of arteether, an experimental antimalarial drug, was used to introduce a hydroxyl group on C‐14. The hydroxyl group was replaced by a deuterium by preparing the tosylate and reductively cleaving it with sodium borodeuteride in DMSO. A reaction sequence to introduce a second label was also demonstrated it involved oxidation of the alcohol, with catalytic quantities of tetra‐n‐propylammonium perruthenate, followed by reduction with sodium borodeuteride to regenerate the alcohol. Use of both reactions sequences yield arteether containing two deuterium.
Radioiodination of 7‐methoxy‐ and 6,7‐dimethoxy‐4‐bromomethylcoumarins
Authors: Baranowska‐Kortylewicz Janina , Kortylewicz Zbigniew P.
Published: October 2006

Two coumarins, 4‐bromomethyl‐6,7‐dimethoxy‐2‐oxo‐2H‐benzopyran (1) and 4‐bromomethyl‐7‐methoxy‐2‐oxo‐2H‐benzopyran (3), were radioiodinated using trifluoroacetyl hypoiodite. The dimethoxy derivative 1 gave only a single regioisomer 3‐[125I]iodo‐4‐bromo‐methyl‐6,7‐dimethoxy‐2‐oxo‐2H‐benzopyran (2). The average yield for no‐carrier‐added preparations of 2 was 30%. 125/127I‐2 and 127I‐2 were produced in over 50% yield. In no‐carrier‐added syntheses 7‐methoxy‐coumarin 3 gave 3‐[125I]iodo‐4‐bromomethyl‐7‐methoxy‐2‐oxo‐2H‐benzopyran(5) as the major product (30%) accompanied by a small amount (3–7%) of the 6‐[125I]iodo‐analog 4. When an equimolar amount of iodide was used (i.e. carrier‐added syntheses) 4 and 5 were produced in over 20% yield each. Under these conditions the 8‐iodo‐regioisomer was not formed from either 1 or 3 possibly as the result of steric effects. Sonication greatly accelerated rates of radioiodination reducing the time required to achieve quantitative substitution of 127I from about 4 h to 20 min.
Stereoselective Synthesis of Stable Isotope Labeled L‐α‐Amino Acids: Synthesis of L−[4−13C] and L−[3,4−13C2]Aspartic Acid
Authors: Lodwig Siegfried N. , Unkefer Clifford J.
Published: October 2006

We have developed a stereoselective route to isotopically labeled L‐aspartic acid using L‐serine as a chiral precursor. Labeled serine, prepared biosynthetically was N‐protected by conversion to the N‐t‐Boc derivative. (N‐t‐Boc)‐[3−13C]Serine is cyclized to its β‐lactone which was treated with potassium [13C]cyanide to yield L‐β‐[3,4−13C2]cyanoalanine. Hydrolysis of the cyanoalanine yielded L‐[3,4−13C2]aspartic acid. Similarly, L‐[4−13C]aspartate was produced from L‐serine and K13CN. Using this route, the L‐enantiomer was produced in 96% excess.
One step synthesis of vanillin d3 (4‐hydroxy‐3‐(methoxy d3)‐benzaldehyde)
Authors: Schneider Serge , Rolando Christian
Published: October 2006

A simple one step synthesis of deuteriated vanillin from 3,4‐dihydroxybenzaldehyde and iodomethane‐d3 in strongly basic medium is described.
Synthesis of [triazole‐3(5)‐14C]‐propiconazole stereoisomers
Authors: Hadjidemetriou Demetrios , Loeffler R. Thomas
Published: October 2006

A preparation of all four stereoisomers of the fungicide and sterol biosynthesis inhibitor propiconazole (1‐[2‐(2,4‐dichlorophenyl)‐4‐propyl‐1,3‐dioxolan‐2‐ylmethyl]‐1H‐1,2,4‐triazole), labelled with [14C] in the triazole ring, is described.
14C‐labeling of a tetrahydroacridine, a novel CNS‐selective cholinesterase inhibitor
Authors: Nishioka Kazuhiko , Kamada Takeshi , Kanamaru Hiroshi
Published: October 2006

9‐Amino‐8‐fluoro‐2, 4‐methano‐1,2,3,4‐tetrahydroacridine citrate (SM‐10888), a novel cholinesterase inhibitor, was labeled with carbon‐14 at C9 of the tetrahydroacridine ring for use in metabolic studies. Carbonation of 2,6‐difluorophenyllithium (3) with [14C]carbon dioxide gave the acid (4). Chlorination of 4 followed by treatment of the resulting acid chloride with ammonia afforded the amide (5). Dehydration of 5 with thionyl chloride and subsequent displacement reaction with ammonia gave the aminobenzonitrile (7). Condensation of 7 with the ketone (8) in the presence of anhydrous zinc chloride yielded the aminoacridine (9), which was treated with citric acid to afford [9‐14C]SM‐10888 (1). The overall yield of 1 was 37% from 2, and the specific activity was 1.35 GBq/mmol.
Synthesis of deuterium labelled hexenols
Authors: Brenstrum Timothy , Brimble Margaret A. , Rush Caroly N. J. , Shaw G. John , Reid David. C. W.
Published: October 2006

Hexenols are important flavour components of fruit and vegetables. We report the synthesis of cis‐3‐hexen‐1‐ol‐6,6,6‐2H3, hexen‐1‐ol‐6,6,6‐2H3, hexan‐1‐ol‐6,6,6‐2H3, cis–2‐hexen‐1‐ol‐6,6,6‐2H3 and trans‐2‐hexen‐1‐ol‐6,6,6‐2H3.
Synthesis of high specific activity tritium labeled (E)‐6‐(bromomethylene)‐tetrahydro‐3‐(1‐naphthalenyl)‐2H‐pyran‐2‐one as a selective probe for calcium‐independent phospholipase a2
Authors: Durley Richard C. , Parnas Barry L. , Weiss Randy H.
Published: October 2006

The synthesis of (E)‐6‐(bromomethylene)‐tetrahydro‐3‐([4‐3H]‐1‐naphthalenyl)‐2H‐pyran‐2‐one at a specific activity of 24.0 Ci/mmol is described. This probe was synthesized to determine whether (E)‐6‐(bromomethylene)‐tetrahydro‐3‐(1‐naphthalenyl)‐2H‐pyran‐2‐one inhibits calcium‐independent myocardial phospholipase A2 irreversibly via covalent modification. The material was synthesized in four steps from 1‐naphthalene acetic acid via [4‐3H]‐1‐naphthaleneacetic acid. The yield from [4‐3H]‐1‐naphthaleneacetic acid was 29.7%. The radiochemical purity of the HPLC‐purified final product was 99.5%.
Synthesis of N‐Acyl‐2‐amino‐2‐deoxy‐[1‐14C]‐glucoses as precursors for the biosynthesis of novel N‐acylneuraminic acids
Authors: Kayser Holger , Zeitler Reinhard , Hoppe Berthold , Reutter Werner
Published: October 2006

N‐Propanoyl‐, N‐butanoyl‐, N‐pentanoyl‐, N‐hexanoyl‐, N‐heptanoyl‐ and N‐crotonoyl‐[1‐14C]‐D‐glucosamine were synthesized from [1‐14C]‐D‐glucosamine and their respective carbonic acid anhydrides as precursors for the biosynthesis of the corresponding N‐acyl neuraminic acids. The N‐acyl‐glucosamines are phosphorylated to their respective phosphate by N‐acetyl‐glucosamine kinase in a rat liver homogenate. These precursors may become valuable tools to investigate the biological role of the N‐acyl side chain of N‐acyl‐glucosamines and N‐acyl neuraminic acids which are components of glycoconjugates.
Marquage par 14C ET 13C de la N acetyl O6 benzyl guanosine
Authors: Madelmont J. C. , Cussac C. , Dupuy J. M. , Rapp M. , Labarre P. , Chabard J. L. , Maurizis J. C. , Sauzieres J. , Baudry J. P. , Godeneche D. , Veyre A.
Published: October 2006

O6 Benzyl N acetyl guanosine a new inhibitor of O6 Alkyl Guanine transferase (O6AGT) was labelled by 14C and 13C on the benzyl methylen group in order to realize a pharmacokinetic study on nude mice grafted with human tumors.

The labelling yield calculated from the precursor (Ba 14 or 13CO3) is in the range of 15%.
Marquage par 14C et 3H du 4,4‐dimethyl‐1‐(methylendioxy‐3,4 phenyl)‐1‐pentene‐3‐ ol ou stiripentol
Authors: Madelmont J. C. , Dupuy J. M. , Rapp M. , Labarre P. , Maurizis J. C. , Lepage F. , Veyre A.
Published: October 2006

4,4‐dimethyl‐1‐(3‐4‐methylenedioxyphenyl)‐1‐pentene‐3‐ol or stiripentol was labelled by 14C and 3H.

14C labelling was performed on the carbone 1 of the pentene group via a four steps procedure after the carbonatation. The radiochemical yield calculated from the precursor (Ba14CO3) is 28%.

3H labelling was performed on the position 3 of the pentene chain by reduction of the corresponding cetone via NaBT4. The radiochemical yield calculated from the precursor (NaBT4) is 40%.
Synthesis of the new immunostimulating agent pidotimod (3‐L‐pyroglutamyl‐L‐thiazolidine‐4‐carboxylic acid) labelled with 14C‐ and 35S‐isotopes
Authors: Ferraboschi Patrizia , Grisenti Paride , Santaniello Enzo , Giachetti Claudio , Zanolo Giovanni , Signorelli Giovanni , Coppi Germano
Published: October 2006

3‐L‐Pyroglutamyl‐L‐thiazolidine‐4‐carboxylic acid (Pidotimod), a new immunostimulating agent, has been prepared labelled with 14C and 35 isotopes starting from L‐[U‐14C]‐glutamic acid 5 and L‐[35S]‐cysteine hydrochloride 6, respectively. In the first synthesis, L‐[U‐14C]‐5 is converted into L‐[U‐14C]‐pyroglutamic acid 2, which was reacted with ethyl L‐thiazolidine‐4‐carboxylate 3 to afford the ester 4, in turn hydrolyzed to [14C]‐Pidotimod 1. In the second synthesis, L‐[35S]‐6 reacted with formaldehyde to give L‐[35S]‐thiazolidine‐4‐carboxylic acid 7, which was coupled with the activated ester of pyroglutamic acid, compound 8, to afford [35S]‐Pidotimod 1. The total activity of [14C]‐Pidotimod was 1.2 mCi (specific activity 5.52 mCi/mmol) and that of [35S]‐Pidotimod was 1.0 mCi (specific activity 9.43 mCi/mmol).
High specific activity steroids II: Microscale synthesis of norgestrel‐[9,11‐3H]
Authors: Huang Glenn T. , McCarthy Keith E. , Parnes Howard
Published: October 2006

The synthesis of the high specific activity (39 Ci/mmole) tritium labelled steroid norgestrel is described. A practical synthesis of the required substrate for tritium incorporation, 18‐methyl‐Δ9(11)‐estradiol‐3‐methyl ether (6), was developed from norgestrel itself. Following reduction with carrier‐free tritium gas, microscale conditions were employed for the conversion of the resulting labelled intermediate (7) back to norgestrel‐[9,11‐3H], including a selective in situ protection of the A‐ring ketone of 19‐norandrost‐4‐ene‐3,17‐dione (11).
The preparation of 2H and 3H‐labelled 7,9‐, and 7,10‐dimethylbenz[c]acridine by catalytic dehalogenation
Authors: Ye Yuerong , Holder Gerald M. , Duke Colin C.
Published: October 2006

Deuterated and tritiated 7,9‐dimethylbenz [c] acridine, and 7,10‐dimethyl‐benz[c]acridine, labelled at the methyl groups, were prepared by catalytic dehalogenation of bromomethyl compouds. For each aza‐aromatic compound three brominated derivatives were prepared and characterized. Incorporation of deuterium occurred more readily at the 9‐ or 10‐methyl groups than the 7‐methyl groups suggesting a large isotope effect for catalytic deuteration.
Synthesis of tritium labelled oximes: 2‐pyridine aldoxime methiodide (2‐PAM) and 1‐(2‐hydroxyiminomethylpyridinium)‐1‐(4‐carboxyamidopyridinium)dimethylether dichloride (HI‐6), with high specific activity
Authors: Balan Ayala , Barness Itzhak , Amitai Gabriel
Published: October 2006

Synthesis of two quaternary pyridinium oximes [3H]2‐PAM and [3H]HI‐6 (18 and 22 Ci/mmole, respectively) was performed by using unlabelled 6‐bromo 2‐pyridine aldehyde (I) as a common starting material. The labelling was based on a catalytic ring‐tritiation of 6‐bromo 2‐diethylketal pyridine followed by acid hydrolysis and reaction with hydroxylamine to yield 6‐[3H]2‐hydroxyiminomethyl pyridine (II). [3H]2‐PAM was obtained by reacting II with methyliodide and [3H]HI‐6 was prepared by alkylation of II with bischlorodimethylether followed by coupling to isonicotineamide. The radiochemical purity of [3H]2‐PAM and [3H]HI‐6 was 98% and at least 95% respectively.
An improved synthetic procedure for L‐3‐iodo‐α‐methyl tyrosine suitable for preparation in kit form
Authors: Trivedi Mahendra A , Carnochan Paul
Published: October 2006

We describe a modified method for the synthesis of radiolabelled L–3–iodo—α–methyl tyrosine (IMT) based on electrophilic iodination using KI and KIO3. Purification of the product using reverse phase HPLC gives reproducible radiochemical yields of 85% and chemical purity >99%. The method has been further modified and simplified for the preparation of IMT in kit form.
Synthesis and in vivo behavior of a copper‐64‐labeled dithiosemicarbazone derivative coupled to a dihydropyridine carrier
Authors: Saji Hideo , Saiga Akihiko , Iida Yasuhiko , Magata Yasuhiro , Yokoyama Akira
Published: October 2006

The dihyropyridine ⇄ pyridinium salt redox delivery system was used to develop a perfusion agent that could be labeled with a generator‐produced positron emitter 62Cu. A 64Cu‐labeled dithiosemicarbazone (DTS) molecule attached to a dihyropyridine carrier (PDTS‐DHC) was synthesized by the simple mixing of 64Cu acetate and Zn‐PDTS‐DHC. The latter was prepared by dithionite reduction of the Zn complex of a corresponding pyridinum precursor (PDTS‐QC+). When injected into mice, 64Cu‐PDTS‐DHC showed a high myocardial uptake and high heart‐to‐blood and heart‐to‐lung ratios. These results demonstrate that it may be possible to develop 62Cu‐PDTS‐DHC compounds as radiopharmaceuticals for myocardial perfusion studies using positron emission tomography.
An investigation into the catalytic deuteration and tritiation of dehydroproline9‐buserelin
Authors: Oehlke J. , Brankoff T. , Schmidt M. , Brudel M. , Kertscher U. , Berger H.
Published: October 2006

For optimizing the catalytic tritiation of peptides, the catalytic deuteration of buserelin and DhP9‐buserelin1 in DMA after reaction of DhP9‐buserelin were comparable in both solvents. The nonspecific incorporation of deuterium found after deuteration of buserelin was clearly lower after reaction in DMA. Tritiation of DhP9‐buserelin in DMA using 85% tritium gas, with conditions optimized by the deuteration experiments, resulted in a specific radioactivity of 1.3 TBq/mmol. 72 and 13 percent of the incorporated radioactivity were found to be associated with proline and histidine, respectively, after acidic hydrolysis.
Stereoselective synthesis of stable isotope labeled L‐α‐amino acids: The enzymatic preparation of 13C‐labeled L‐glutamic acids
Authors: Goux Warren J. , Rench Linda , Weber Denise S.
Published: October 2006

We have developed methods for the preparation of L‐glutamic acid, isotopically labeled with 13C, using commercially available purified enzymes. The procedure is sufficiently versatile that L‐glutamic acid may be labeled at any carbons or any combination of carbons using 13C‐labeled pyruvate, acetate and bicarbonate as isotopically labeled precursors. Using the strategy outlined, we have demonstrated the methodology using as an example the preparation of millimolar quantities of L‐[1‐13C], L‐[4‐13C], L‐[5‐13C] and L‐[1,3,4‐13C3]glutamic acid in a one‐pot incubation. We also outline methods for the preparation of 13C‐labeled L‐malate and citrate.
Preparation and biodistribution of a technetium cationic complex ‐ [TcIII(sacac)2en(PPh3)2]+
Authors: Vavouraki H. , Papadopoulos M. , Mastrostamatis S. , Varvarigou A. D. , Psilla M. , Chiotellis E.
Published: October 2006

The new, “mixed‐ligand”, TcIII‐N, N′‐ethylene‐bis‐(acetylacetone‐thioiminato)‐bis‐(triphenylphosphine)–hexafluorophosphate complex, corresponding oxo‐technetium (V) precursor with triphenylphoshine, in methanol. It was characterized by elemental analysis, IR, UV‐Vis and 1H NMR spectroscopy and HPLC. Biodistribution studies showed a considerable heart uptake, but rather slow blood clearance and hepatic elimination.
Synthesis of 15N and 17O labelled phosphoramide mustards
Authors: Ludeman Susan M. , Shulman‐Roskes Ellen M. , Gamcsik Michael P. , Hamill Terence G. , Chang Young H. , Koo Kyo I. , Colvin O. Michael
Published: October 2006

The cyclophosphamide metabolite phosphoramide mustard (PM) was synthesized with isotopic enrichment at each nitrogen and oxygen site. Sequential reaction of N,N‐bis(2‐chloroethyl)phosphoramidic dichloride [Cl2P(O)N(CH2CH2Cl)2] with benzyl alcohol and ammonia gave N,N‐bis(2‐chloroethyl)phosphorodiamidic acid phenylmethyl ester [BzO(H2N)P(O)N(CH2CH2Cl)2]. Catalytic hydrogenation of this benzyl ester followed by the addition of cyclohexylamine (CHA) provided PM as the CHA salt. Incorporation of 15NH3 into this general scheme gave PM with a 15NH2 moiety. Glycine‐15N was converted to bis(2‐chloro‐ethyl)amine‐15N hydrochloride which, in turn, provided for N,N‐bis(2‐chloroethyl)phosphoramidic‐15N dichloride. Use of this compound in the general synthetic pathway yielded PM°CHA with 15N in the mustard moiety. 17O‐Enriched PM was generated through the use of benzyl alcohol‐17O. To obtain the alcohol, labelled benzaldehyde was made by exchange with 17OH2 and was then reduced with sodium borohydride.
Radiation‐induced tritium labelling and product analysis
Authors: Peng C. T.
Published: October 2006

By‐products formed in radiation‐induced tritium labelling are identified by co‐chromatography with authentic samples or by structure prediction using a quantitative structure‐retention index relationship. The by‐products, formed from labelling of steroids, polynuclear aromatic hydrocarbons, 7‐membered heterocyclic ring structures, 1,4‐benzodiazepines, 1‐haloalkanes, etc. with activated tritium and adsorbed tritium, are shown to be specifically labelled and anticipated products from known chemical reactions. From analyses of the by‐products, one can conclude that the hydrogen abstraction by tritium atoms and the substitution by tritium ions are the mechanisms of labelling. Classification of the tritium labelling methods, on the basis of the type of tritium reagent, clearly shows the active role played by tritium atoms and ions in radiation‐induced methods.
Deuterium exchange labelling of substituted aromatics using [IrH2(Me2CO)2(PPh3)2]BF4
Authors: Heys J. R. , Shu A. Y. L. , Senderoff S. G. , Phillips N. M.
Published: October 2006

Deuterium exchange labelling experimets were conducted on several series of compounds, including para‐substituted benzoate esters, para‐substituted N,N‐dimethylbenzamides, and mono‐para‐substituted benzophenones, using [IrH2(Me2CO)2(PPh3)2]BF4as catalyst and deuterium gas as the source of isotope. In most cases, labelling was efficient and regioselective, with deuterium appearing in the positions ortho to the carbonyl‐containing functional group. Apparent from the results of these experiments was that, in each case the para‐substituted rings were labelled more rapidly or to a greater extent than the corresponding unsubstituted rings, regardless of the identity of the substituent.
Synthesis of [3″‐3H]taxol and [13‐3H]taxol1
Authors: Taylor George F. , Thornton Stephen S. , Tallent C. Ray , Kepler John A.
Published: October 2006

7‐Trietylsilylbaccatin III (11) was coupled with cis‐1‐benzoyl‐3‐triethylsiloxy‐4‐(3′‐bromophenyl)azetidin‐2‐one. Hydrolysis of the silyl groups gave 3″‐bromotaxol which was reduced with tritium gas to give[3″‐3H]taxol with specific activity of 19.3 Ci mmol. Reduction of 7‐triethylsilyl‐13‐oxobaccatin III with [3H]borane‐tetrahydrofuran complex gave 7‐triethylsilyl[13‐3H]baccatin III (17). Coupling of 17 with cis‐3‐triethylsiloxy‐4‐phenyl‐(3R,4S)‐azetidin‐2‐one and hydrolysis gave [13‐3H]taxol with specific activity of 1.66 Ci/mmol.
Synthèse d'un herbicide tritié à forte activité spécifique: Le Thifensulfuron méthyle
Authors: Bastide J. , Ortega F.
Published: October 2006

In order to study the binding on acetolactate synthase, a tritiated herbicide sulfonylurea (thifensulfuron methyl) of high specific activity was synthesized. By use of C3H3I for esterification of an acid group, a rapid incorporation of tritium into this compound may be achieved.
Synthesis of [18F]fluoroethoxy‐benzovesamicol, a radiotracer for cholinergic neurons
Authors: Mulholland G. Keith , Jung Yong‐Woon , Wieland Donald M. , Kilbourn Michael R. , Kuhl David E.
Published: October 2006

Full experimental details are given for the preparation of [18F]fluoroethoxy‐benzovesamicol, (−)‐(2R, 3R)‐trans‐2‐hydroxy‐3‐(4‐phenylpiperidino)‐5‐(2‐[18F]fluoroethoxy)‐1,2,3,4‐tetralin, a new fluorine‐18 labeled cholinergic neuron mapping agent for use in positron emission tomography (PET). This radiotracer was made by nucleophilic radiofluorination of tosyloxyethoxy‐benzovesamicol, followed by reverse phase HPLC purification, in decay corrected radiochemical yield exceeding 60%.
Synthesis of 5‐[123I]iodonicotinamide and biodistribution in rat
Authors: Bergström K. A. , Lötjönen S. , Kuikka J. T. , Penttilä P. , Mussalo H. , Hiltunen J. , Länsimies E.
Published: October 2006

5‐[123I] iodonicotinamide (NAM) was prepared by halogen exchange iodination from 5‐bromonicotinamide. In order to study biodistribution and brain accumulation 123I‐NAM was injected into rats. Dynamic gamma camera images were collected. The rats were sacrificed and tissue specific activities were measured. From dynamic images the maximum brain (head) activity after 30 minutes was 8.3% of the injected dose and after 110 minutes, 4.5%. 123I‐NAM was cleared by the kidneys. Radioactivity in the tissue samples of brain, kidney, blood, liver, spleen, lung, muscle, heart, bone and thyroid decreased over the course of 110‐160 minutes, indicating rapid washout of the tracer. In conclusion the uptake in the brain and washout of 123I‐NAM was rapid. 123I‐NAM may be useful as a brain imaging agent.
Synthesis of [3H]‐labelled glucobrassicin, a potential radiotracer for metabolic studies of indole glucosinolates
Authors: Chevolleau S. , Joseph B. , Rollin P. , Tulliez J.
Published: October 2006

Glucobrassicin, an indole glucosinolate widespread in cruciferous plants, appears to be involved in anticarcinogenic activity via its breakdown products. In order to study the “in vivo” metabolism of glucobrassicin, we have synthesized the 5‐[3H]‐indol‐3‐ylmethyl glucosinolate (3H‐labelled glucobrassicin) starting from artificial peracetylated 5‐bromoindol‐3‐ylmethyl glucosinolate. The labelled compounds were characterized by radio‐HPLC and FAB mass spectrometry.
Synthesis of (+)‐N‐(6‐Ethoxy[2,4‐3H]phenyl)‐N‐(1,2,2‐trimethylpropyl)‐2‐nitroethene‐1,1‐diamine ([3H]BAY x 9228)
Authors: Pleiß U. , Lenfers J.‐B. , Schmitt P.
Published: October 2006

The synthesis of tritium‐labelled (+)‐N‐(6‐Ethoxy[2,4‐3H]phenyl)‐N‐(1,2,2‐trimethylpropyl)‐2‐nitroethene‐1, 1‐diamine ([3H]BAY x 9228) a pottassium channel opener, was achieved by dehalogenation of a dibrominated racemic precursor using palladium hydroxide on charcoal as catalyst. The separation into the enantiomers was achieved by an chiral HPLC‐column. The specific activity was 47.9 Ci/mmol (1.8 TBq/mmol).
Stereoselective synthesis of [11 β‐3H]prostaglandin E1
Authors: Bundy G. L. , Easter J. A. , Banitt L. S. , Philopoulos Y. , Sinha A. J. Wickrema , Hsi R. S. P.
Published: October 2006

This report describes an efficient stereoselective synthesis of [11β‐3H]prostaglandin E1 ([11β‐3H]PGE1). The key multiply protected 11‐keto intermediate was prepared in only three steps from PGE1. Reduction of the ketone function at C‐11 with sodium borodeuteride and sodium borotritide, followed by sequential removal of protecting groups, afforded PGE1 labeled with deuterium and tritium, respectively, at the 11‐beta position. The reduction and deprotection were accomplished in one reaction flask without requiring purification of intermediates. Trace amounts of C11‐epimer formed in the reduction were readily separated by means of preparative reversed‐phase HPLC. Using sodium borotritide of nominally 67 Ci/mmol, we obtained [11β‐3H]PGE1 with specific activity of 15 Ci/mmol. A disposition study in the monkey with intravenous administration of this material indicated excellent in vivo metabolic stability of the 11β‐tritium label.
Synthesis of 14C‐labelled sodium pariprazole (E3810)
Authors: Tagami Katsuya , Chiku Shigeru , Sohda Shigeru
Published: October 2006

Sodium pariprazole (E3810), an inhibitory of H+,K+‐ATPase, was synthesized labelled with carbon‐14, starting from 2‐mercapto[2‐14C]‐benzimidazole 1 with a specific activity of 888 MBq/mmol. It was obtained in 49.3% radiochemical yield with a radiochemical purity of more than 98%.
Radiolabelling of pharmaceutical dosage forms by neutron activation of samarium‐152
Authors: Awang M B , Hardy J G , Davis S S , Wilding I R , Parry S J
Published: October 2006

Samarium‐152 can be activated in a neutron flux for the labelling of pharmaceutical dosage forms for evaluation by gamma scintigraphy. The samarium is incorporated as samarium oxide powder which is available with 152Sm in its natural isotopic abundance or isotopically enriched. The yield of 153Sm was reduced considerably following the neutron activation of the non‐isotopically enriched oxide. This can be attributed to the high neutron capture by 149Sm present in the non‐isotopically enriched oxide. In order to keep the mass of the added oxide powder to the minimum and also to reduce the neutron irradiation time, it is recommended that samarium oxide enriched with 152Sm should be used routinely when radiolabelling pharmaceutical dosage forms.
Low cost production of perdeuterated biomass using methylotrophic yeasts
Authors: Haon Stéphane , Augé Sophie , Tropis Marielle , Milon Alain , Lindley Nic D.
Published: October 2006

Three strains of methylotrophic yeasts, Candida boidinii, Pichia angusta (previously Hansenula polymorpha) and Pichia Pastoris, were studied for their capacity to grow on methanol in deuterated media. Growth rates, determined relative to the extent of deuteration of water and/or methanol, showed that water deuteration was the major limiting factor. After adaptation to deuterium by progressive transfer through media of increasing deuteration, growth rates were diminished relative to those obtained on hydrogenated media of identical salts composition: the two Pichia species retained the highest growth rates (μ=0.02 h−1) in the fully deuterated medium. Perdeuterated biomass (16 g) was obtained in a 1 liter fed‐batch fermentation and the extent of deuteraton of isolated ergosterol has been shown to be 97.5% by mass spectrometric analysis.
C10‐Oe‐N‐(4‐azido‐5‐125iodo salicyloyl)‐β‐alanyl‐β alanyl ryanodine (Az‐βAR), a novel photo‐affinity ligand for the ryanodine binding site
Authors: Bidasee Keshore R. , Besch Henry R. , Kwon Sangyeol , Emmick Jeffrey T. , Besch Kurt T. , Gerzon Koert , Humerickhouse Rod A.
Published: October 2006

A high affinity, photoactivatable, radio‐iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium‐release‐channel, C10‐Oeq‐N‐(4‐azido‐5‐125iodo salicyloyl)‐β‐alanyl‐β‐alanyl ryanodine (Az‐βAR), was synthesized at a specific activity of 1400mCi/mmol. Prepared by condensing the versatile synthon, N‐(4‐azido‐5125iodo salicyloyl)‐β‐alanine with C10‐Oeq‐β‐alanyl ryanodine, Az‐βAR, like [3H] ryanodine, does not demonstrate saturation binding kinetics. 127Az‐βAR exhibits an IC50 of 27.2 ± 2 × 10−9 M (mean ± SD) compared to ryanodine's 6.2 ± 0.4 × 10−9 M for the ryanodine receptor/calcium release channel of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle.
Synthesis of a radiotracer for studying σ receptors in vivo using PET: (+)‐N‐[11C]‐benzyl‐N‐normetazocine (1S, 5S,9S‐(+)‐cis‐2‐[11C]‐2′‐hydroxy‐5,9‐dimethyl‐6,7‐benzomorphan)
Authors: Musachio John L. , Mathews William B. , Ravert Hayden T. , Carroll F. Ivy , Dannals Robert F.
Published: October 2006

(+)‐N‐[11C]‐Benzyl‐N‐normetazocine (1S,5S,9S‐(+)‐cis‐2‐[11C]‐benzyl‐2′‐hydroxy‐5,9‐dimethyl‐6,7‐benzomorphan), a potent and selective ligand for the σ receptor, was prepared by N‐benzylation of (+)‐cis‐N‐normetazocine with [α‐11C]‐benzyl iodide in ethanol using sodium hydrogen carbonate as the proton acceptor. The radiotracer was purified by semi‐preparative reverse‐phase HPLC. The average specific activity was 746 mCi/μmol calculated at end‐of‐synthesis (EOS). The average time of synthesis including formulation was 35 minutes.
2‐Amino‐2′‐[18F]fluorobenzhydrols, intermediates for the synthesis of [2′‐18F]‐1,4‐benzodiazepine‐2‐ones
Authors: Johnström Peter , Stone‐Elander Sharon
Published: October 2006

A method for synthesizing 18F‐labelled 2‐amino‐2′‐fluorobenzhydrols under nocarrier‐added conditions for use as radiolabelled intermediates in the synthesis of[2′‐18F]‐1,4‐benzodiazepine‐2‐ones is presented. Anilinodichloroborane reagents were formed by the reaction of boron trichloride with 4‐chloro‐N‐methylaniline, 6a, 4‐nitro‐N‐methylaniline, 6b, 4‐nitro‐N‐ethylaniline, 6c, and 4‐chloro‐N‐(2,2,2‐trifluoroethyl)aniline, 6d. 2‐[18F]Fluorobenzaldehyde, 5, synthesized in 55–70% yields by the nucleophilic aromatic substitution of 2‐nitrobenzaldehyde with the Kryptofix/K+ complex of [18F]F−, was subsequently reacted with the anilinodichloroborane coupling reagents with aromatic substitution occurring ortho to the amino group. The resulting 2‐amino‐2′‐[18F]fluorobenzhydrols, 7a ‐ 7d, were produced in conversions of 60–95% with reaction time ⩽ 10 min at room temperature or 60°C, depending on the aniline used. The total synthesis time, including evaporation of the target water, was 60–65 min. The total radiochemical conversions were of the order of 50–65% for 7a ‐ 7c and 35–45% for 7d, decay‐corrected and based on [18F]F−.
The synthesis of [10‐13C]bilirubin IXα
Authors: Sturrock E. D. , Bull J. R. , Kirsch R. E.
Published: October 2006

The total synthesis of [10‐13C]bilirubin IXα, the principal waste product of haem degradation, is described. Site specific labelling was accomplished by the Vilsmeier formylation of one of the dipyrrolic fragments using [1‐13C]dimethylformamide. The penultimate dehydrohalogenation reaction was complicated by a competing elimination reaction which yielded a bridged biliverdin derivative. [10‐13C]bilirubin IXα was prepared in an overall yield of 6% (from the step where 13C was introduced) with quantitative isotopic incorporation.