bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of [3H] tyr‐D‐thr‐gly‐phe(pN3)‐leu‐thr an irreversible photoaffinity probe for the opioid δ receptors
Authors: Gacel G. , Fellion E. , Roques B. B. , Genet R. , Morgat J. J. , Fromageot P.
Published: October 2006

In a previous work, the synthesis of [3H] Tyr‐D‐Thr‐Gly‐Phe‐Leu‐Thr (DTLET), a highly selective probe for δ opioid receptors has been described. More recently, Az‐DTLET (Tyr‐D‐Thr‐Gly‐Phe (pN3)‐Leu‐Thr) has been shown to be a specific and irreversible photoaffinity ligand for δ opioid sites. In the present paper, we reported the synthesis of the 3,5 dibromotyrosyl 4′‐amino‐3′,5′ diiodophenylalanyl precursor of [3H] Az‐DTLET. Reductive tritiation by exchange with 3H2 followed by the introduction of the azido group leads to the labelled azido analog of enkephalin with specific activity of 50 Ci/mmole. This compound is now used to characterize the subunits of opioid δ receptors and to visualize these targets in the brain by electron microscopy.
Multi‐13 C‐labelled inhibitors of tubulin assembly: 5‐substituted methyl N‐(1H‐benzimidazol‐2‐YL)carbamates
Authors: Cheung H. H. Andrew , Chau Diem Dieu , Lacey Ernest
Published: October 2006

Eight methyl N‐(1H‐benzimidazol‐2‐yl) carbamates with various 5‐substituents were synthesized, each 13C‐enriched at carbon 2, and the carbonyl and methoxy carbons. Five were prepared by cyclization involving the appropriate 4‐substituted 1,2‐diaminobenzene (C6H5CO‐, CH3CH2CH2O‐, CH3CH2S‐, C6H5S‐ and CH3CH2CH2‐), and methyl‐13C N‐[imino(methylthio) methyl‐13C]carbamate‐13C or methyl N, N'‐bis(methoxy‐13C‐carbonyl‐13C)carbamimidothionate‐ 13C. The latter were prepared from commercially available 13C‐enriched (91‐92 atom %) carbon tetrachloride, methanol, and thiourea. The remaining three (5‐substituents: C6H5CH(OH)‐, C6H5SO‐ and CH3CH2CH2SO‐) were prepared by side‐chain reduction or oxidation. The 1H‐ and 13C‐NMR, and the methane CI mass spectral data of the products and intermediates are presented.
Folate analogues: 27. syntheses of 14carbon‐labeled 10‐deazaaminopterin and 10‐ethyl‐10‐deazaaminopterin
Authors: Nair M. M. , Nanavati Nitin T.
Published: October 2006

10‐Deazaaminopterin (1) and 10‐Ethyl‐10‐deazaaminopterin (2) labeled uniformly with 14C at the glutamate moiety were prepared by the following procedure. Uniformly labeled L‐glutamic acid was converted to its dimethyl ester (3). 4‐Amino‐4‐deoxy‐10‐deazapteroic acid (4) and 4‐amino‐4‐deoxy‐10‐ethyl‐10‐deazapteroic acid (5) were converted to their respective mixed anhydrides 6 and 7 with isobutylchloroformate. Reaction of 6 and 7 with labeled dimethyl‐L‐glutamate gave dimethyl‐10‐deazaaminopterin (8) and dimethyl 10‐ethyl‐10‐deazaaminopterin (9) respectively, which on mild alkaline hydrolysis gave the target compounds 1 and 2 in 22‐25% yield, based on the amount of radiolabeled glutamic acid used.
Synthesis of (R)‐(+)‐3H‐etomidate
Authors: Janssen Cor G. M. , Thijssen Jos B. A. , Verluyten Willy L. M. , Heykants Jozef J. P.
Published: October 2006

Etomidate, (R)‐(+)‐ethyl‐1‐(1‐phenylethyl)‐1H‐imidazole‐5‐carboxylate, is a short‐acting hypnotic. A new synthesis, featuring optical resolution on a non‐radioactive precursor and introduction of the tritium label by reductive dehalogenation, is described.

The title compound was obtained at a specific activity of 3.77. Ci/mmol and a 99.9 % HPLC purity.
Synthesis of 1,2,3,4‐tetrahydrocarbazole‐9a‐13C and carbazole‐9a‐13C
Authors: Pickering R. E. , Wysocki M. A. , Eisenbraun E. J. , Pell R. J. , Gearhart H. L. , Hamming M. C.
Published: October 2006

The synthesis of 1,2,3,4‐tetrahydrocarbazole‐9a‐13C and carbazole‐9a‐13C via cyclohexanone‐1‐13C, prepared in turn from carbon dioxide‐13C and 1,5‐pentanedimagnesium bromide is described.
Direct deuterium labelling of xanthone with the lithium salt of 1,3‐diaminopropane‐N, N, N',N'‐d4
Authors: Abrams Suzanne R.
Published: October 2006

A direct method for selective deuteration of xanthone 1 employing the lithium salt of 1,3‐diaminopropane‐N, N, N',N'‐d4 is described. Dibenzofuran is also found to be deuterated selectively under these conditions.
Radioactively labelled epoxides. part V. Tritium labelled K‐region oxides and trans‐dihydrodiols of pyrene, benzo[a]pyrene and dibenz[a, h]anthracene
Authors: Setiabudi Frans , Oesch Franz , Platt Karl L.
Published: October 2006

Tritium labelled K‐region oxides of pyrene, benzo[a]pyrene and dibenz[a,h]anthracene have been prepared by cyclization of the corresponding trans‐dihydrodiols which were obtained by reduction of K‐region quinones with sodium borotritide in the presence of oxygen. This synthetic pathway not only yields two metabolically important radioactively labelled derivatives of polycyclic aromatic hydrocarbons in a simple and efficient manner, but also requires a rather inexpensive source of tritium.
Synthesis of [4,4,4‐2H3]butanoic acid
Authors: Visser Frans R.
Published: October 2006

The synthesis of [4,4,4‐2H3]butanoic acid with 10% yield from deuterated acetic acid is described. The structure is confirmed by n.m.r. and mass spectroscopy and the percentage of labelling is established as >98.5% [2H3]butanoic acid.
Synthesis of [14C]amiflamine ‐ an MAO‐A inhibitor
Authors: Sahlberg Christer , Gawell Lars
Published: October 2006

Amiflamine ( (S)‐(+)‐2‐(4‐dimethylamino‐2‐methylphenyl)‐1‐methylethylamine) is a potent, selective, and reversible MAO‐A inhibitor. Carbon‐14 labelled amiflamine (8) with a specific activity of 8.1 mCi/mmol was prepared. The key‐step in the synthesis is a Cu(I)‐catalyzed reaction of an organometallic derivative obtained from compound (6) with 14CH3I. Also described is the synthesis of the optically active compound (6).
Synthesis of [2‐14C]‐1‐(2‐deoxy‐2‐fluoro‐β‐D‐arabinofuranosyl)‐5‐fluoro(chloro)uracil
Authors: Misra Hemant K. , Wiebe Leonard I. , Knaus Edward E.
Published: October 2006

The reaction of [2‐14C]‐2,4‐bis‐O‐(trimethylsilyl)uracil (2) with 3‐O‐acetyl‐5‐O‐benzoyl‐2‐deoxy‐2‐fluro‐α‐D‐arabinofuranosyl bromide (3) yielded the 3‐O‐acetyl‐5‐O‐benzoyl nucleoside 4 which was hydrolyzed with methanolic ammonia to afford [2‐14C]‐1‐(2‐deoxy‐2‐fluro‐β‐D‐arabinofuranosyl)uracil (5) in 55% radiochemical yield with a specific activity of 2 mCi/mmol (74 MBq/mmol). The reaction of 5 with molecular fluorine and chlorine in glacial acetic acid at 25°C afforded the 5‐fluoro‐6a and 5‐chloro‐6b analogues of [2‐14C]‐1‐(2‐deoxy‐2‐fluoro‐β‐D‐arabinofuranosyl)uracil in 85.6 and 87.9% isolated radiochemical yield, respectively. Similar radiochemical yields were obtained when [2‐14C]uracil having a specific activity of 12 mCi/mmol (444 MBq/mmol) was utilized.
The Synthesis of 8‐β‐[(Methylsulfinyl‐[18O])‐methyl]‐6‐propylergoline
Authors: Wheeler William J.
Published: October 2006

The synthesis of 18O‐labeled 8‐β‐[(methylsulfinyl)‐methyl]‐6‐propyl‐ergoline (pergolide‐[18O]‐sulfoxide) of undetermined stereochemistry by the reaction of 8‐β‐(methylthiomethyl)‐6‐propyl‐ergoline (pergolide) with bis‐(4‐methoxyphenyl)‐selen‐[18O]‐oxide in acetic acid is described. Although the yields were low and the incorporation of 18O was not high, this procedure represents a convenient method for the preparation of 18O‐labeled sulfoxides of pergolide and other sulfides present in compounds for which the usual methods are inappropriate.
Modified and improved method for synthesis of p‐halogenated‐N‐isopropylamphetamine leading to synthesis of “no carrier added” I‐131 iodoamphetamine
Authors: Najafi A.
Published: October 2006

I‐123 labeled N‐isopropyl‐p‐iodoamphetamine (IMP) has been shown to be an important and useful radiopharmaceutical for measurement of cerebral blood flow (1–4). Since substituted amphetamines have a strong pharmacological activity, the synthesis of “No Carrier Added” (NCA) labeled IMP would be desirable (5). In this paper we would like to report a modified and improved method for the synthesis of para‐halogenated‐N‐isopropylamphetamine and the preparation of NCA I‐131 IMP. This procedure involves a labeling reaction using I‐131 sodium iodide and para‐bromo‐N‐isopropyl amphetamine (BrMP) followed by HPLC separation of I‐131 IMP and BrMP using reverse phase chromatography.
Synthesis of double carbon‐14 labeled CI‐9371 and CI‐942, potential new anticancer drugs
Authors: Hicks James L. , Huang C. C. , Showalter H. D. Hollis
Published: October 2006

CI‐937 and CI‐942, compounds which show potent anticancer activity, were synthesized with double labeled high specific activity carbon‐14. The key intermdiate in the synthesis, 3,6‐dichloro‐[dicarbonyl‐14C2]phthalic anhydride was made by treating 2‐bromo‐1,4‐dichlorobenzene with n‐butyllithium and 14CO2 to give 2,5‐dichloro[carboxy‐14C]benzoic acid, which was converted to its diethylamide. Ortho‐directed lithiation followed by a second carboxylation produced the ortho acid‐amide. Hydrolysis and dehydration generated the anhydride. Friedel‐Crafts acylation of the anhydride with 1,4‐benzenediol gave 1,4‐dichloro‐5,8‐dihydroxy[9,10‐14C2]‐9,10‐anthracenedione. Protection and hydrazination gave a chloroanthrapyrazole intermediate which was converted into [14C2]CI‐937 or [14C2]CI‐942 in two steps. The specific activities of the final compounds were 196 μCi/mg and 182 μCi/mg respectively.
A simple, efficient synthesis of 3′‐D3‐mevalonic acid
Authors: Hawkins Douglas R. , Calvin Melvin
Published: October 2006

3′‐D3‐Mevalonic acid was required to study triterpenoid biosynthesis. It was synthesized by a simple route in a 24% yield from D3‐acetic acid‐D. The product was characterized as the crystalline salt: N, N'‐dibenzylethylenediammonium bis‐(3,5‐dihydroxy‐3‐(D3‐methyl)‐pentanoate) and was shown by mass spectroscopy and 1H‐NMR to be essentially 100 atom% deuterium labelled.
Synthesis of tritium‐labeled (3)‐O‐(3‐hydroxypropyl)‐17α‐estradiol chromium tricarbonyl: The first radioactive transition metal carbonyl steroid hormone
Authors: Top Siden , Vessieres Anne , Jaouen Gérard
Published: October 2006

3‐O‐(3‐hydroxypropyl)‐17β‐estradiol chromium tricarbonyl 1 has been labeled in the 17α position with deuterium or tritium. These complexes were prepared by reduction of the corresponding estrone by NaBD4 or NaB[3H]4. The radioactive hormone was obtained in a solid state with a specific activity of 4.1 Ci/mmole, which is sufficiently high for hormone receptor binding studies.
Preparation of E‐ and Z‐5‐deuterioadamantan‐2‐ol
Authors: Lin Man‐Hua , Le Noble W. J.
Published: October 2006

The title synthesis can readily be carried out on a 50 mg scale or more, starting with the 54/46 mixture of E‐ and Z‐5‐bromoalcohols obtained from the sodium borohydride reduction of the ketone. The key feature on which the synthesis dependes is the fact that the Z‐trimethylsilyl bromoether is reduced by zinc borohydride (and ‐deuteride) in benzene much faster than the E‐ epimer.
Synthesis of specifically labelled L‐phenylalanines using phenylalanine ammonia lyase activity
Authors: Hädener A. , Tamm Ch.
Published: October 2006

Specifically labelled L‐phenylalanines have been prepared using a variety of classical synthetic methods in combination with phenylalanine ammonia lyase (PAL) enzyme activity of the yeast Rhodosporidium toruloides ATCC 10788 or Rhodotorula glutinis IFO 0559, respectively. Thus, L‐[2‐2H]phenyl‐[2‐2H]alanine (5) was formed from (E)‐[2,2′‐2H2]cinnamic acid and ammonia in 46% yield, whereas L‐phenyl‐[2‐13C,15N]alanine (9) was obtained from (E)‐[2‐13C]cinnamic acid in 45% overall yield using an 8.3‐fold excess of 15NH4Cl and repeating the reaction after recovery of unchanged labelled material. Generally, labelled cinnamic acids were recovered in pure form from the reaction mixture, with a loss of 6‐8%. Likewise, unchanged 15NH3 was reisolated as 15NH4Cl after steam distillation with overall losses of less than 4%. Labelled cinnamic acids were prepared by Knoevenagel condensations between appropriately labelled benzaldehydes and malonic acids. [2‐2H]Benzaldehyde was obtained from 2‐bromotoluene by decomposition of the corresponding Grignard reagent with 2H2O and subsequent oxidation. Since simple molecules, most of them commercially available in labelled form or otherwise easily accessible, may serve as starting material, and due to its defined stereochemistry, the reaction catalyzed by PAL opens a short and attractive route to specifically labelled L‐phenylalanines.
Synthesis of 1‐[(1,4‐benzodioxan‐2‐ylmethyl)amino]‐3‐(3‐pyridazinon‐2‐YL)‐[3‐14C]propane hydrochloride (gyki‐12743), a new antihypertensive agent
Authors: Birkás‐Faigl E. , Zólyomi G. , Makk N. , Kasztreiner E.
Published: October 2006

A new antihypertensive agent, GYKI‐12743, has been labelled with carbon‐14 via a six‐step synthesis. The label was introduced by chain elongation of an appropriate precursor using potassium [14C]cyanide as radioactive starting material. A satisfactory overall yield, 44.7 %, relative to KCN was achieved.
Synthèse et distribution tissulaire chez le rat du Phénylacétate de Diéthylamino‐2 éthyle marqué par 14C
Authors: Moreau M. M. , Michelot J. , Labarre P. , Parry D. , Veyre A.
Published: October 2006

2‐Diethylaminoethyl phenylacetate was labelled by 14C in two positions:

‐ on the carboxylic group by means of 14C‐phenylacetic acid.

‐ on the aminoethanol part using 14C ethanolamine as intermediate.

Biodistribution studies were performed in rats for the two labellings after i.v. administration of the compound.
Synthesis of S‐[3H]‐DO‐710, a benzamide ligand of the D2‐dopamine receptor and of S‐[3H]‐azidosulpride, its photoactivable analog
Authors: Rognan D. , Mann A. , Hamdi P. , Wermuth C. C. , Sokoloff P. , Schwartz J. J. , Roy J. , Morgat J. J.
Published: October 2006

The preparation of the tritium labelled benzamides, S‐[3H]‐DO‐710 and S‐[3H]‐azidosulpride is reported. The synthesis involves enantioselective preparation of the pyrrolidinyl moiety, reductive tritiation of an allylic precursor and conversion of an amino, to an azido function.

Both labelled ligands are D2‐dopaminergic antagonists, useful in binding experiments and to achieve covalent bonds after light exposure at the receptor site level.
Synthesis and enzymatic decarboxylation of 6‐bromo‐L‐dopa, a potential brain tracer for L‐dopa
Authors: Wong Michael , de Jesus Onofre T.
Published: October 2006

Direct bromination of L‐dopa with stoichiometric amounts of molecular bromine was found to yield 6‐bromo‐L‐dopa as the sole product. This determination was made using liquid chromatography with electrochemical detector, mass spectroscopy, and proton NMR. 6‐Bromo‐L‐dopa was found to be a substrate of an isolated decarboxylase enzyme although the rate of decarboxylation was much slower than that for L‐dopa. These results suggest that a radiobrominated L‐dopa analog may be a suitable PET or SPECT tracer for L‐dopa in the brain.
Synthesis of 3H‐ and 14C‐cisapride
Authors: Janssen C. C. M. , Lenoir H. H. C. , Thijssen J. J. A. , Knaeps A. A. , Heykants J. J. P.
Published: October 2006

Cisapride, (±)‐cis‐4‐amino‐5‐chloro‐N[1‐[3(4‐fluorophenoxy)propyl]‐3‐methoxy‐4‐piperidinyl]‐2‐methoxybenzamide, is a new gastrokinetic drug with a potent stimulating effect on the gastrointestinal motor activity. Metabolic studies required the synthesis of cisapride labelled at one of the three major moieties. Hence, cisapride was tritiated either in the fluorophenyl moiety by means of reductive dehalogenation, or via reductive amination in the piperidine ring.

14C‐Cisapride was labelled in the benzamide function. The title compounds were obtained at a specific activity of 17.0 Ci/mmol, 59.8 mCi/mmol and 7.8 mCi/mmol, respectively and with HPLC purities of > 98 %.
Perdeuteration at the 9,10‐positions of 9,10‐dibromoanthracene and anthracene‐d10
Authors: Pickering R. E. , Eisenbraun E. J. , Doughty D. , Strube M. M. , Gammon B. E.
Published: October 2006

Na/D2O/THF is highly effective in perdeuteration of anthracene‐d10 and 9,10‐dibromoanthracene at the 9,10‐positions to give 9,10‐dihydro‐9,10‐d2‐anthracene‐d10 and 9,10‐dihydro‐9,9,10,10‐d4‐anthracene respectively.
Synthesis of tri‐, tetra‐, and penta‐deuterated forms of vitamin a
Authors: Robert Bergen H. , Furr Harold C. , Olson James A.
Published: October 2006

The synthesis of 20,20,20‐trideutero, 14,20,20,20‐tetradeutero, 12,14,20,20,20‐pentadeutero, and 10,19,19,19‐tetradeutero analogs of retinoic acid ethyl ester and retinyl acetate, by a modified Wittig‐Horner synthesis, is described. Deuterium was introduced by base‐catalyzed exchange into appropriate intermediates. The 10,19,19,19‐2H4‐vitamin A, because of its high isotopic integrity (>98% 2H4), is the preferred analog for biological studies of vitamin A metabolism.
Synthesis of c‐9‐14C‐1,8‐dihydroxy‐3‐carboxyanthraquinone
Authors: De Witte P. , Lemli J.
Published: October 2006

The synthesis of C‐9‐14C‐rhein is reported, 14CO2 is used as a 14C‐source. After preparing 14C‐1,8‐dimethoxy‐3‐methylanthraquinone by a condensation reaction, the product is demethylated and the 3‐methyl group converted to the corresponding 3‐carboxy group. The radio‐active yield of the total synthesis, starting with 1 Ci 14CO2 is 6,9% (6,9 mCi); 352 mg 14rhein is produced with a specific activity of 55,7 mCi/mmol.
Synthesis of f‐18 labelled fluoro‐melatonins and 5‐hydroxy‐fluoro‐tryptophans
Authors: Chirakal Raman , Sayer Brian G. , Firnau Gunter , Garnett E. S.
Published: October 2006

Reaction of dilute [F‐18]fluorine gas with either melatonin or 5‐hydroxy‐tryptophan in hydrogen fluoride at −70°C gives 6‐fluoro‐melatonin or 4‐ and 6‐fluoro‐5‐hydroxytryptophan. They are of potential use in Positron Emission Tomography to image the binding sites for melatonin and to study the metabolism of serotonin.
Synthesis of [14C]‐labelled AY‐30,068
Authors: Hicks D. R. , Hangeland J. J. , Mobilio D. , Delange B.
Published: October 2006

[14C]AY‐30,068 (cis‐1,8‐diethyl‐2,3,4,9‐tetrahydro‐4‐(2‐propenyl)‐1H‐carbazole‐1‐acetic acid), a potent analgesic agent, was prepared by incorporating [14C]methyl iodide via a Wittig reaction. The intermediate aldehyde was synthesized in six steps from cis‐1‐ethyl‐2‐oxo‐4‐(2‐propenyl)cyclohexaneacetic acid methyl ester. Three batches of the [14C]labelled AY‐30,068 were produced, giving a combined overall yield of 9% from [14C]methyl iodide (sp. act. 51.2, 17.7 and 4.4 μCi/mg; 97.5, 98.3, and 98.6% radiochemcical purity, respectively).
Synthesis of D/L‐ and L‐SE‐[methyl‐11C]selenomethionine
Authors: Någren Kjell , Långström Bengt
Published: October 2006

The syntheses of D/L‐ and L‐Se‐[methyl‐11C]selenomethionine are reported. The Se‐benzyl selenohomocysteines were deprotected in sodium/liquid ammonia and the selenide anions generated in situ were alkylated with [11C]methyl iodide to give, after purification by LC, the products in 80 to 85 % radiochemical yield, with a radiochemical purity higher than 99 % within 30 min and with a specific radioactivity of 20 to 200 mCi/μmol. The enantiomeric purity of the L‐compound, determined by LC, was higher than 99 %.
Synthesis of two S‐(methyl‐3H)‐labelled enkephalins and S‐(methyl‐14C)substance P
Authors: Någren Kjeli , Franzèn Henry M. , Ragnarsson Ulf , Långström Bengt
Published: October 2006

The synthesis of 3H‐labelled Met‐enkephalin and Tyr‐D‐Ala‐Gly‐Phe‐Met‐NH2 (DALA) and 14C‐labelled Substance P (SP) from previously described, fully protected intermediates is reported. The labelled peptides were prepared by methylation with (3H)‐ or (14C)methyl iodide of the sulphide anions formed on deprotection of the corresponding S‐benzyl‐homocysteine precursors with sodium in liquid ammonia. After purification by LC, the labelled peptides were obtained in radiochemical yields in the range of 9 to 24 % with a radiochemical purity higher than 97%. The specific radioactivities of the 3H‐ and 14C‐labelled products, corresponding to the labelled methyl iodides used, were 80 mCi/μmol and 60 μCi/‐μmol, respectively.
Synthesis of three 11C‐labelled methionine‐containing enkephal in analogues
Authors: Någren Kjell , Ragnarsson Ulf , Långström Bengt
Published: October 2006

The synthesis of three S‐[methyl‐11C]‐labelled enkephal in analogues, iyr‐D‐Ala‐Gly‐Phe‐Met‐NH2, Tyr‐D‐Ala‐D‐Ala‐Phe‐Met‐NH2 and Tyr‐D‐Met‐Gly‐Phe‐Pro‐NH2, from the corresponding S‐benzyl‐homocysteine‐containing peptides is reported. The protected pentapeptide amides were prepared by (3+2) fragment condensations in solution. These peptides were subsequently deprotected with sodium in liquid ammonia and the sulphide anions formed alkylated with [11C]‐methyl iodide to give the S‐[methyl‐11C]‐labelled enkephalins. After purification by preparative LC, these labelled peptides were obtained in 55 to 75 % radiochemical yield, decay corrected, based on the [11C]methyl iodide produced, within 30‐40 min from start of the synthesis of this reagent. The radiochemical purities of the products were higher than 98 %, and the specific activity was in the order of 20‐200 mCi/μmol.
Preparation of carbon‐11 labelled prazosin, a potent and selective α1‐adrenoreceptor antagonist
Authors: Ehrin Erling , Luthra Sajinder K. , Crouzel Christian , Pike Victor W.
Published: October 2006

The α1‐adrenoreceptor antagonist, Prazosin : 2‐[4‐(2‐furoyl) piperazin‐1‐yl]‐4‐amino‐6,7‐dimethoxyquinazoline, has been labelled with carbon‐11 for in vivo studies of α1‐adrenoreceptors using positron emission tomography. The preparation of [2‐11C] furoyl chloride, from cyclotron‐produced [11C] carbon dioxide, and its reaction with the secondary amine, 2‐(piperazin‐1‐yl)‐4‐amino‐6,7‐dimethoxyquinazoline, provides a fast (35 min) route to carbon‐11 labelled prazosin in high radiochemical yield (30‐40 %, decay‐corrected) with high specific activity (26‐37 GBq/μmol, 0.7‐1.0 Ci/μmol).
Synthesis of [14C]propane
Authors: Dass Desmond V. , Martin R. Wayne , Odell Allan L. , Quinn Gregory
Published: October 2006

[14C]propane of high chemical and radiochemical purity has been prepared from [14C]acetone via [1,3‐14C]acetone semicarbazone.
Synthesis of 1‐([1‐14C] cyclohexyloxycarbonyloxy) ethyl 7β‐[2‐(2‐aminothiazol‐4‐YL)acetamido]‐3‐[[[1‐(2‐dimethylamino‐ethyl)‐1H‐tetrazol‐5‐YL]thio]methyl]ceph‐3‐EM‐4‐carboxylate dihydrochloride ([14C]SCE‐2174)
Authors: Watanabe Masazumi , Tada Norio , Imanishi Masayuki , Yamaoka Masayoshi
Published: October 2006

1‐(Cyclohexyloxycarbonyloxy)ethyl 7β‐[2‐(2‐amino‐thiazol‐4‐yl)acetamido]‐3‐[[[1‐(2‐dimethylaminoethyl)‐1H‐tetrazol‐5‐yl]thio]methyl]ceph‐3‐em‐4‐carboxylate dihydrochloride (SCE‐2174), a new orally active cephalosporin, was labeled with carbon‐14 starting from [1‐14C]cyclohexanol (1). 1‐Chloroethyl [1‐14C]cyclohexyl carbonate (3) obtained by acylation of 1 with 1‐chloroethyl chloroformate (2) was converted to iodide (4) which was condensed with the potassium salt of Cefotiam (5). [14C]SCE‐2174, having a specific activity of 672 MBq/mmol, was obtained in 13% overall radiochemical yield and had a radiochemical purity of 92%.
Synthesis of six specifically deuterated analogs of 1,2‐dibromo‐3‐chloropropane
Authors: Omichinski James G. , Nelson Sidney D.
Published: October 2006

The convenient preparation of six selectively deuterated analogs of 1,2‐dibromo‐3‐chloropropane have been described. The compounds were prepared by direct chlorination of the correspondingly deuterated 2,3‐dibromopropanol derivatives using N‐chlorosuccinimide and triphenylphospine. Spectral analysis revealed that the isotope incorporation was high and specific in all cases.
Synthesis of deuterated 1,2,3,4‐tetrahydroisoquinolines
Authors: Meese Claus O. , Ebner Thomas
Published: October 2006

The synthesis of five 1,2,3,4‐tetrahydroisoquinolines (2), which were either randomly labelled (1,1,3,3,4,4‐2H6,2b) or regioselectively labelled (1,1‐2H2,2c; 3,3‐2H2, 2d; 4,4‐2H2, 2e) from isoquinoline (4), indan‐2‐one (7), and phenylacetonitrile (11) is described. These deuterated bases were used in the preparation of labelled analogues of the antihypertensive agent debrisoquine.
The synthesis of deuterium labeled T‐2 toxin
Authors: Michaud Dennis P. , Karger B. L. , Vouros Paul
Published: October 2006

We report the synthesis of isotopically pure trideuteriated T‐2 toxin, a useful internal standard for mycotoxin analysis. Peracetylation of HT‐2 toxin with hexadeuteriated acetic anhydride, followed by selective hydrolysis of the C‐3 acetate afforded the desired compound in good yield.
Effects of reaction conditions on rates of incorporation of no‐carrier added F‐18 fluoride into several organic compounds
Authors: Korguth Ml , Degrado Tr , Holden Je , Gatley Sj
Published: October 2006

Apparent rate constants (fractional incorporation per minute per mole of organic reactant) were determined for reaction of no‐carrier added F‐18 fluoride with several aliphatic and aromatic substrates in acetonitrile or DMSO. No large differences were seen between tetraethylammonium and potassium Kryptofix‐2,2,2 as supporting cation. Three hexose derivatives with triflate or cyclic sulfate leaving groups all gave apparent rate constants (obtained by dividing fractional incorporation by time in minutes and by molar concentration of reactant) near 0.4 at 23° and 5 at 55°. An aliphatic iodide reacted ten times more slowly. Aromatic substrates tested showed a wide range of rate constants from >50 at 23° (isotope exchange in 2,4‐dinitrofluorobenzene) to 0.6 at 134° (p‐nitroacetophenone).
Labeling of a serotoninergic ligand with 18F : [18F] setoperone
Authors: Crouzel C. , Venet M. , Irie T. , Sanz G. , Boullais C.
Published: October 2006

Setoperone has been labeled with 18F to visualize the serotoninergic receptors by positron emission tomography. The synthesis is carried out by a nucleophilic substitution from a nitro derivative of setoperone with 18F−. The synthesis of nitro‐derivative is described as well as the different trials of recovery of ion 18F− from neon or aqueous target. The considered technique of labeling allow to obtain from 7.4 GBq (200 mCi) 18F, 1.5 to 2 GBq (40–50 mCi) of [18F]setoperone, 110 minutes after the end of bombardment. The specific activity obtained from this quantity of radioactivity is about 37 GBq/μMol (1 Ci/μMol).
Alternative synthesis of no‐carrier‐added 2‐deoxy‐2‐[18F]fluoro‐D‐glucose using [18F] fluoride ion
Authors: Haradahira Terushi , Maeda Minoru , Kojima Masaharu
Published: October 2006

Two alternative routes to no‐carrier‐added synthesis of 2‐deoxy‐2‐[18F]fluoro‐D‐glucose (2‐18FDG) involving nucleophilic displacements of methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐O‐(trifluoromethanesulfonyl) ‐β‐D‐mannopyranoside (1) and 1,6‐anhydro‐3, 4‐di‐O‐benzyl‐2‐O‐(trifluoromethanesulfonyl)‐β‐D‐mannopyranose (2) are described. The triflates (1 and 2) reacted with aminopolyether (Kryptofix 222) supported potassium [18F]fluoride and tetra‐n‐butylammonium [18F]fluoride in acetonitrile to give methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐2‐[18F] fluoro‐β‐D‐glucopyranoside (3) and 1,6‐anhydro‐3,4‐di‐O‐benzyl‐2‐deoxy‐2‐[18F] fluoro‐β‐D‐glucopyranose (4), respectively. The displacement yield with 1 was consistently higher than that with 2. Hydrolysis of 3 with 6N HCl, followed by passage through an ion retardation resin column and a neutral alumina column, gave 2‐18FDG in 34–43% overall radiochemical yield without correction for decay. Removal of the protecting groups from 4 with 6N HCl or 50% CH3SO3H led to incomplete hydrolysis. The total preparation time was about 80 min from start of the radiofluorination.
Synthesis of 14C‐labeled stepholidine
Authors: Liu Yang , Xin Zhang
Published: October 2006

(8‐14C)Stepholidine was synthesized by Mannich condensation of 7‐benzyloxy‐1‐(4‐benzyloxy‐3‐hydroxybenzyl)‐6‐methoxy‐1,2,3,4‐ tetrahydroisoquinoline (2) with (14C)formalehyde at pH 6.4 followed by methylation and debenzylation in 32% radiochemical yield.
The comparative synthesis of 18F‐fluorophenylalanines by electrophilic substitution with 18F‐F2 and 18F‐AcOF
Authors: Murakami M. , Takahashi K. , Kondo Y. , Mizusawa S. , Nakamichi H. , Sasaki H. , Hagami E. , Iida H. , Kanno I. , Miura S. , Uemura K.
Published: October 2006

Fluorination with 18F‐F2 and 18F‐AcOF were compared for the synthesis of 18F‐fluorophenylalanines. L‐phenylalanine in CF3COOH trapped 18F‐AcOF more effectively than 18F‐F2. The main product was ortho‐18F‐fluorophenylalanine when 18F‐AcOF was used as a reagent. Lower radiochemical yield of 18F‐fluorophenylalanines and significant formation of by‐product were observed in the case of 18F‐F2.
Synthesis of [14C]‐labelled dihydropyridine calcium channel entry blockers: Nicardipine‐[4‐14C] and RS‐93522‐[4‐14C]
Authors: Parnes Howard , Huang Glenn T. , Shelton Emma J.
Published: October 2006

The Hantzsch synthesis has been applied to the general preparation of 4‐aryl‐dihydropyridines labelled in the metabolically stable 4‐position of the dihydropyridine ring. The synthesis is based on the preparation of a key common intermediate, m‐nitrobenzaldehyde‐[formyl‐14C], in high yield from Ba14CO3.
A short radiosynthesis of natural juvenile hormone III, methyl [12‐3H]‐(10R)‐10,11‐epoxyfarnesoate
Authors: Eng Wai‐Si , Prestwich Glenn D.
Published: October 2006

A new asymmetric synthesis of natural JH III from methyl farnesoate allows introduction of tritium from sodium borotritide into the 12‐methyl group. Selective allylic oxidation followed by Sharpless epoxidation of the (E)‐allylic alcohol gives an epoxy alcohol (>97% e.e.), which is oxidized to the aldehyde. Sodium borotritide (65 Ci/mmol) reduction of the aldehyde is followed by tosylation, iodide displacement, and cyanoborohydride displacement to give [3H]‐(10R)‐JH III, specific activity 14 Ci/mmol.
Synthesis of [14α, 15α‐3H]‐norgestrel
Authors: Wagner H. , Römer J.
Published: October 2006

The preparation of the well‐known gestogen norgestrel in a tritium labelled form is described. Starting material was 18‐methyl‐3‐methoxy‐estra‐1,3,5(10),8,14‐pentaen‐17B‐ol acetate. In a four step synthesis 17α‐ethinyl‐17B‐hydroxy‐18‐methyl‐[14α,15α‐3H]‐estr‐4‐en‐3‐one was obtained with a specific activity of 52 Ci/mmol and a radiochemical purity > 99 %.
A chiral synthesis of (2S, 3S)‐phenylalanine‐3‐2H via boronic esters
Authors: Matteson Donald S. , Beedle Ellen C. , Christenson Erik , Dewey Michael A. , Peterson Mark L.
Published: October 2006

Reduction of (s)‐pinanediol (S)[(phenyl) (chloro)‐methyl]boronate (1) with lithium triethylborodeuteride yielded (s)‐pinanediol (R)‐[(phenyl)methyl]boronate‐α‐2H (2). The chiral purity of 2 was measured via peroxidic oxidation to (S)‐benzyl alcohol‐α‐2H (3), which was analyzed with an NMR chiral shift reagent. (Dichloro‐methyl)lithium converted 2 to (s)‐pinanediol (1S,2S)‐1‐chloro‐2‐phenylethylboronate‐2‐2H (4), which with sodium azide yielded (s)‐pinanediol (1R,2S)‐1‐azido‐2‐phenylethylboronate‐2‐2H (5). (Dichloromethyl) lithium with 5 yielded (s)‐pinanediol (1S, 2S,3S)‐1‐chloro‐2‐azido‐3‐phenylpropylboronate‐3‐2H (6), which was oxidized by sodium chlorite to (2S,3S)‐2‐azido‐3‐phenylacetic acid‐3‐2H (7). Hydrogenation of 7 yielded (2S,3S)‐phenylalanine‐3‐2H (8) in high diastereomeric and enantiomeric purity.
Synthesis of 14C‐labeled and stable isotope‐labeled CGS 16617
Authors: Chaudhuri Naba K. , Markus Bohdan , Sung Ming‐Sang
Published: October 2006

The synthesis of a 14C‐labeled and two stable isotope‐labeled analogs of CGS 16617 is described. The synthetic method involved the preparation of tetrahydro‐3‐bromo‐1‐benzazepin‐2‐one, labeled with a 14C or four deuterium atoms, followed by introduction of two side chains at 1‐ and 3‐positions. The labeled bromobenzazepinones were prepared by Beckmann rearrangement of bromooximes of α‐tetralones, obtained by cyclization of labeled benzenebutanoic acids. The 14C‐labeled acid was prepared by hydrolysis of the nitrile, prepared by reaction of 3‐bromopropylbenzene and K14CN. The tetradeutero acid was prepared from ethyl phenylpropynoate by catalytic reduction of the triple bond with deuterium gas, followed by reduction of the deuterated ester with lithium aluminum hydride and conversion of the resulting alcohol into the carboxylic acid. The acetic acid side chain was introduced by N‐alkylation with ethyl bromoacetate or ethyl bromoacetate‐1,2‐13C2 followed by hydrolysis, and the L‐lysine side chain, by reaction with L‐(−)‐3‐amino‐caprolactam followed by hydrolysis of the caprolactam ring.
Synthesis of carbon‐14 labeled (±)‐2‐methyl‐3,3‐diphenyl‐3‐propanolamine (2‐MDP)
Authors: De Costa Brian , Thurkauf Andrew , Jacobson Arthur E. , Rice Kenner C.
Published: October 2006

The preparation of 14C labeled (±)‐2‐methyl‐3,3‐diphenyl‐3‐propanolamine (3) from [14C]‐carbonyl‐benzophenone is described.
The synthesis of [14C] and [3H2] SK&F l‐94901. A novel thyromimetic
Authors: Crowe A M , Lawrie K W M , Saunders D
Published: October 2006

A novel thyromimetic SK&F L‐94901, L‐3,5‐dibromo‐3′‐(6‐oxo‐1, 6‐dihydro pyridazin‐3‐ylmethyl) thyronine, has been labelled with 14C and 3H for drug metabolism and nuclear binding studies. A six stage synthesis from [β‐14C] tyrosine is described. The overall radiochemical yield was 13.7%.

Syntheses of [3H2] SK&F L‐94901 of 1.22Ci mmol−1 and 13.9Ci mmol−1 are described, and the instability of these compounds noted.
35S‐labelled thiophosphorylated derivative of inositol trisphosphate
Authors: Folk P. , Kmoníčková E. , Krpejšová L. , Strunecká A.
Published: October 2006

We have prepared the [35S] thiophosphate labelled inositol trisphosphate and [32P]phosphate labelled inositol trisphosphate (IP3) from human erythrocytes. These compounds were used as substrates for the inositol trisphosphate 5‐phosphomonoesterase assay in human erythrocyte membranes. During 60 min incubation with the enzyme, the 35S‐labelled IP3 was not hydrolyzed, meanwhile the 32P‐labelled IP3 was broken down to 19.8 ± 2.4 %. This suggests that due to the presence of thiophosphate in the molecule the 35S‐labelled IP3 cannot serve as substrate for inositol trisphosphate 5‐phosphomonoesterase. The [35S] thiophosphorylated derivative thus represents a nonhydrolyzable analogue of IP3 and could be used in the study of its second messenger role.
Autoradiography with photographic paper of thin‐layer chromatograms of radiocarbon‐labelled compounds
Authors: Sugimoto Yasuo , Ohta Yoshihiro , Tamaoki Bun‐Ichi
Published: October 2006

By exposing a thin‐layer chromatogram of 4‐14C‐labelled steroids directly onto a sheet of photographic paper, evidence was obtained on the distribution of radioactivity on the chromatogram. This method offers a relatively easy way to make a copy for publication and recording.
Labelling of a new serotoninergic ligand : [18F]ritanserin
Authors: Crouzel C. , Venet N. , Sanz G. , Denis A.
Published: October 2006

Ritanserin has been labelled with 18F to visualize the serotoninergic receptors by Positron Emission Tomography (PET). The synthesis was carried out by a nucleophilic substitution of a nitro substituent of a nitrophenylketone by 18F− and then addition of a Grignard reagent to the ketone followed by dehydration of the tertiary alcohol so formed.

The total time to have [18F]ritanserin ready for injection into a patient was 150 minutes (after the end of bombardement for the 18F production [18O (p,n) 18F]).

The labelling technique described was used to obtain 1.1 to 1.5 GBq (30 to 40 mCi) of [18F]Ritanserin with a specific activity of 44 GBq/μmol (1.2 Ci/μmol) starting from 18.5 GBq (500 mCi) 18F.
Isosteres Oxygenes d'Hydroxy‐di‐n‐Propylaminotetralines Syntheses de Monomethoxy et Monohydroxy‐ (DI‐N‐Propylamino)‐3 Chromannes [n‐Propyl‐3H] Racemiques: Nouveaux Radioligands des Sites de Liaison Serotoninergiques 5‐HT1a et Dopaminergiques D2
Authors: Cossery J. M. , Perdicakis C. , Coudert G. , Guillaumet G. , Pichat L.
Published: October 2006

Oxygen Isosteres of hydroxy‐di‐n‐propylaminotetralines. Syntheses of racemic monomethoxy and monohydroxy‐3‐(di‐n‐[3H‐propyl] amino) chromanes: new Radioligands for 5–HT1A and D2 receptors sites labelling.

Condensation of monomethoxy salicylaldehydes: 4a–d with nitroethanol gave methoxy‐3‐nitro‐2H chromenes 5a–d which were reduced with LAH into methoxy‐3‐amino chromans 6a–d. Two syntheses of 2‐hydroxy‐6‐methoxy‐benzal‐dehyde: 4a were described. N‐alkylations of 6a–d were carried out a/ by Borch procedure b/ by n‐propylation with propyl iodide in presence of bases c/ by allylation in presence of bases. Methoxy‐3‐(diallyl‐amino) chromans: 13a–d were catalytically reduced with hydrogen (Pd/C in methanol) into mixtures of methoxy‐3 (di‐n‐propylamino) chromans 2a–d and methoxy‐3‐ (n‐propylamino) chromans resulting from the hydrogenolysis of one allyl group.

Methoxy‐3‐dialkylamino chromans 2a–d and 13a were O‐demethylated either by boiling 48% HBr or by BBr3 in CH2Cl2.

Catalytic hydrogenation with tritium of precursors 13a–d and15a in methanol in presence of 10% Pd/C gave [3H] – 5. OH‐DPLC: 3a; [3H] 5. OMe‐DPAC: 2a and the isomers: 2b‐2d which were purified by HPLC, analyzed by reversed HPLC, 3H‐NMR, M.S. (spec. radioactivity: 37.2‐80 Ci/μMole. Radiochemical purity: 98.3–99.6%).
A convenient enzymatic preparation of specifically‐labelled geraniol
Authors: Banthorpe Derek V. , Branch Stephanie A.
Published: October 2006

Geraniol was formed in high (up to 36%) yield when equimolar quantities of isopentenyl and 3,3‐dimethylallyl pyrophosphates (1 mmole) together with inhibitors of the isomerase that interconverts them were incubated with a strictly defined cell‐free extract from flowerheads of Rosa dilecta cv. Lady Seaton. The C5 units were incorporated in toto with essentially (>98%) complete position specificity. A simple route is thus available, given the appropriately labelled C5 precursors, for the preparation of geraniol and thence by standard chemical routes of its isomers nerol and linalool and their pyrophosphates with any chosen carbon atom specifically labelled at isotope abundances suitable for biosynthetic studies. Similarly, any desired 2H or 3H labelled geraniol or its relatives could in principle be prepared with both regio‐ and stereo‐specificity.
Synthesis of [3H]‐desciclovir, prodrug of the antiviral acyclovir
Authors: Moorman Allan R. , Hill John A.
Published: October 2006

The title compound was prepared by direct radiochemical synthesis from 2‐acetylamino‐9‐[(2‐hydroxyethoxy)methyl]‐9H‐purine. The product had a specific activity of 21.5 Ci mmol−1 and a radiochemical purity of 99.2%. The general approach described may be applicable to other “acyclic” nucleosides.
Immunoaffinity methods in radiolabelling of antibodies. A critical assessment using i‐125‐anti‐β‐chorionic gonadotropin as an example
Authors: Li‐Cheng Fu , Andres Roger Y.
Published: October 2006

The usefulness of immunoaffinity methods for the preparation of biologically fully active radiolabelled antibodies was investigated, using anti‐β‐chorionic gonadotropin as a model substance. Immunoaffinity purification increased the fraction of antigen binding antibody after previous labelling from 25 % to 81 %. Radiolabelling of anti‐β‐chorionic gonadotropin while bound to the antigen resulted in biologically highly active material, possibly due to the protection of the immunologically active sites on the antibody during the labelling procedure. Immunoaffinity purification prior to labelling did not result in biologically active material. Elution yields from immunoaffinity supports were generally low.
Synthesis of substituted bromobenzene derivatives via bromoanilines. A moderately selective ortho‐bromination of [14c]‐aniline
Authors: Weller Paul E. , Hanzlik Robert P.
Published: October 2006

The synthesis of [14C]‐labeled bromobenzene, 2‐bromophenol, 4‐bromophenol, 1,2‐dibromobenzene, 2‐bromobenzonitrile, 2‐bromotoluene, and 2‐bromoanisole are reported. [14C]‐Aniline is selectively monobrominated to ortho‐and para‐bromoanilines in 5 to 3 ratio. The separated bromoanilines are diazotized and either reduced, hydrolyzed, coupled to bromide, coupled to cyanide, or coupled to carbon. 2‐Bromophenol is O‐methylated to 2‐bromoanisole.
Preparation of18F‐labelled N‐fluoropyridinium triflate
Authors: Oberdorfer Franz , Hofmann Evelyn , Maier‐Borst Wolfgang
Published: October 2006

N‐Fluoropyridinium triflate was labelled with18F proceeding through N‐trimethylsilylpyridinium triflate and [18F]F2diluted to 1% in Ne. A typical experiment afforded this new fluorine‐18 transfer reagent with up to 46% radiochemical yield. The specific activity of18F‐labelled N‐fluoropyridinium triflate was determined by iodometric titration to be in the range of 4·10−8mg/Bq (1.5 mg/mCi; 1.67·10−4Ci/μM).
Synthesis of tritium‐labelled fenoxycarb and S‐31183, two phenoxyphenyl ether insect growth regulators
Authors: Boehm Marcus F. , Prestwich Glenn D.
Published: October 2006

Using 4‐(m‐bromophenoxy)phenol as an intermediate, two brominated phenoxyphenyl ether IGRs were prepared. Reductive tritiodebromination of the bromo IGRs furnished high specific activity tritium‐labelled fenoxycarb and S‐31183, which can be used to study the molecular action of these two potent juvenoid‐type IGRs.
Synthesis of 14C and 3H labeled arabinosyl‐5‐azacytosine
Authors: Taylor George F. , Zamani Kahveh , Kepler John A.
Published: October 2006

Arabinosyl‐[6‐3H]5‐azacytosine is prepared by catalytic exchange with tritium gas. The preparation of arabinosyl‐[2,4‐14C]5‐azacytosine from barium [14C]carbonate via [U‐14C]guanylurea and [2,4‐14C]5‐azacytosine is described.
Investigation of the catalytic deuteration of N‐acetyl‐DL‐3,4‐dehydroproline amide
Authors: Oehlke J. , Niedrich H. , Zöpfl H.‐J. , Franke P.
Published: October 2006

As a model for the tritium labelling of peptides the catalytic deuteration of N‐acetyl‐DL‐3,4‐dehydroproline amide was investigated by means of mass spectrometric measurements. The unwanted incorporation of hydrogen instead of deuterium, found especially in the presence of water, was compensated partially by an incorporation of deuterium proceeding additionally to the saturation of the double bond. Both effects were most intensive in the presence of water and rose with ascending catalyst amounts and descending pH.
The preparation of 18O, 15N, and 14C enriched N‐methyl‐2‐(4‐nitrophenoxy)‐ethanamine hydrochlorides and N‐methyl‐N‐(2‐hydroxyethyl)‐4‐nitroanilines
Authors: Yilmaz Ibrahim , Shine Henry J.
Published: October 2006

Preparations are described of the hydrochloride of partially enriched N‐methyl‐2‐(4‐nitrophen[18O]oxy)ethanamine, N‐methyl‐2‐(4‐nitrophenoxy)‐ethan[15N]amine, and N‐methyl‐2‐(4‐nitro[1‐14C]phenoxy)ethanamine, designated herein as [18O]‐2, [15N]‐2, and [14C]‐2, respectively. By base‐catalyzed rearrangement these enriched ethanamine derivatives were converted, respectively, into N‐methyl‐N‐(2‐[18O]hydroxyethyl)‐4‐nitroaniline, N‐methyl‐N‐(2‐hydroxyethyl)‐4‐nitro[15N]aniline, and N‐methyl‐(2‐hydroxyethyl)‐4‐nitro[1‐14C]aniline, designated as [18O]‐3, [15N]‐3, and [14C]‐3.
Synthesis of methotrexate‐3‐15N‐2‐15NH2. A convenient method for preparation of guanidiine‐15N3
Authors: Degraw Joseph I. , Ryan Kenneth J. , Colwell William T. , Arnold John R. P. , Roberts Gordon C. K.
Published: October 2006

Condensation of guanidine‐15N3 with 4‐[N(2‐amino‐3‐cyano‐5‐pyrazinyl‐methyl)‐N‐methylamino] benzoic acid (1) in refluxing methanol afforded 4‐amino‐4‐deoxy‐N10‐methylpteroic‐3‐15N‐2‐15NH2 (2). The mass spectrum clearly indicated no label introduction at the pterin N1 position. Coupling of 2 with diethyl L‐gluatmate and subsequent alkaline hydrolysis yielded methotrexate‐3‐15N‐2‐15NH2 (4). Triply 15N‐labeled guanidine was readily prepared from thiocyanic‐15N acid (derived from KSC15N) and ammonia‐15N by heating the resultant ammonium thiocyanate‐15N2 at 180°C, followed by isolation as the water insoluble picrate salt.
New stereospecific labeling of mevalonolactone at position C‐5 with deuterium and tritium
Authors: Zamir Lolita O. , Nguyen Cong‐Danh
Published: October 2006

The synthesis of (3RS) (5R)[5‐2H]‐, (3RS) (5S) [5‐2H]‐and (3RS) (5S) [5‐3H]‐mevalonolactones are described.
Synthesis of tritium‐labelled 9‐deazainosine
Authors: Singh Ambarish K. , Klein Robert S.
Published: October 2006

The synthesis of labelled 9‐deazainosine (1a,b) from the fully blocked 9‐deazainosine (2) is achieved in six steps by selective detritylation, oxidation of the C‐5′ hydroxyl group, followed by purification via its N,N′‐diphenylimidazolidine derivative, deprotection to obtain the 5′‐aldehyde, borotritide reduction, and deisopropylidenation to give the labelled nucleoside. The sequence is of general utility in labelling nucleosides at the C‐5′ position for biochemical studies.
Synthesis of high specific activity 125I‐ and 123I‐labelled enantiomers of 2,5‐dimethoxy‐4‐iodophenylisopropylamine (DOI)
Authors: Mathis C. A. , Hoffman A. J. , Nichols D. E. , Shulgin A. T.
Published: October 2006

The syntheses of high specific activity 125I‐ and 123I‐labelled (R)‐ and (S)‐2,5‐dimethoxy‐4‐iodophenylisopropylamine (DOI) are described. Three radiosynthetic routes, two of which involved use of amine protecting groups and one of which utilized the free base, were compared to maximize the radiochemical yields and specific activities of the products. The method which provided the highest yields utilized the free amine with no protecting group in aqueous acidic solvent with chloramine‐T oxidant. Final radiochemical yields of ca. 80% were achieved for both 125I and 123I incorporation. The specific activities of the 125I‐labelled products averaged 1100 Ci/mmol and the 123I‐labelled products were > 20,000 Ci/mmol.
Synthesis of tritium labelled (3R*, 5S*)‐3, 5‐dihydroxy‐9, 9‐diphenyl‐6, 8‐nonadienoate
Authors: Wint Lewin T. , McCarthy Peter A.
Published: October 2006

Methyl (3R*, 5S*)‐(E)‐3,5‐dihydroxy‐9,9‐diphenyl‐6,8‐nonadienoate (1) is a competitive inhibitor of HMG‐CoA reductase, the rate‐limiting step in cholesterol biosynthesis. We synthesized 1 with a tritium label at C3 in order to investigate tissue selectivity. The synthesis began with β‐phenyl‐ cinnamaldehyde which was homologated to (E)‐5,5‐diphenyl‐2,4‐pentadienal in three steps. Addition of the dianion of methyl acetoacetate gave methyl (E)‐5‐hydroxy‐ 9,9‐diphenyl‐3‐oxo‐6,8‐nonadienoate. Diastereoselective introduction of the tritium label was achieved using tritium labelled sodium borohydride, triethylborane and a catalytic amount of pivalic acid. The radiochemical yield for this step was 7.5 %, the specific activity was 13.3 mCi/mmole, and the product was >95% radiochemically pure. This method may be applicable to the preparation of other radiolabelled HMG‐CoA reductase inhibitors which possess a 3,5‐dihydroxy acid moiety.
Preparation of trans‐octaethylchlorin‐D2(α,β),‐D2(γ,δ), and ‐d4 as well as octaethylporphyrin‐d2 using acid‐catalyzed exchange reaction
Authors: Salehi Asaad , Fonda Harold N. , Oertling Anthony W. , Babcock Gerald T. , Chang Chi K.
Published: October 2006

Preparation of three forms of selectively deuterated trans‐octaethylchlorin (t‐OEC) and octaethylporphyrin‐d2 (OEP‐d2) with high isotopic purity using acid catalyzed hydrogen‐deuterium exchange reaction is described. Deuterated t‐OEC labeled at γ,δ‐methine carbons was prepared directly by equilibrating t‐OEC in D2SO4:D2O (6:1, v/v) at room temperature for 20 hours. t‐OEC labeled at all four methine carbons was prepared as above in 72 hours. And t‐OEC labeled at α,β‐positions was obtained by “back‐exchange” of t‐OEC‐d4 under the protio condition, H2SO4:H2O (6:1, v/v), in 18 hours. The DDQ dehydrogenation of either dideuterochlorin species resulted in the formation of OEP‐d2. The isotopic purities of all deuterated compounds were over 98 percent except for t‐OEC‐d2(α,β) which was estimated to be ∼ 90 percent by proton NMR spectroscopy.
Synthesis of [4‐methyl‐14C]epostane
Authors: Johnston D. , Duncan D. R.
Published: October 2006

A synthetic procedure for producing [4‐methyl‐14c]epostane is described. The radiolabel is introduced using [14C]formaldehyde as shown in the scheme.
13C‐Markierung der Seitenketten von Mitoxantrone
Authors: Blanz Joachim , Zeller Klaus‐Peter
Published: October 2006

5,8‐Bis‐{[1‐13C]‐{[2‐[(2‐hydroxyethyl)amino]ethyl]amino}}‐1,4‐dihydroxy‐9,10‐anthracenedione dihydrochloride is synthesized in 28% yield from [13C]‐sodium cyanide via a five step sequence. The described synthesis of the sidechain, 2‐[(2‐aminoethyl)amino]ethanol, allows the labelling of each position of the carbon skeleton by taking use of only one intermediate, which is easy to prepare in very good yield.