Journal of Labelled Compounds and Radiopharmaceuticals

VERCOUILLIE, Johnny; TARKIAINEN, Jari; HALLDIN, Christer; EMOND, Patrick; CHALON, Sylvie; SANDELL, Johan; LANGER, Oliver; GUILLOTEAU, Denis

doi: 10.1002/jlcr.436pmid: N/A

The serotoninergic system is involved in a variety of neurological and psychiatric disorders. Exploration of the serotonin transporters (5‐HTT) in living human brain by PET would be of great value for better understanding, diagnosis and therapeutic follow up of these diseases. In order to obtain a selective radioligand to explore the 5‐HTT by PET we report the synthesis of (11C)N,N‐dimethyl‐2‐(2‐amino‐4‐iodophenylthio)‐benzylamine ((11C)ADAM). The precursor for labelling N‐demethyl ADAM, was obtained in five steps using 2,5‐dibromonitrobenzene and 2‐thio‐N‐methylbenzamide as starting material. (11C)ADAM was synthesised by N‐alkylation of the precursor using (11C)methyl iodide in DMF. The incorporation yield of (11C)methyl iodide was in the range of 50 to 70%. Finally (11C)ADAM was obtained in 30 minutes synthesis time including HPLC and with a radiochemical purity better than 99%. Copyright © 2001 John Wiley & Sons, Ltd.

Marthi, K.; Bender, D.; Smith, D.F.

doi: 10.1002/jlcr.437pmid: N/A

As part of our program to develop PET tracers for investigating monoaminergic processes in the brain, mianserin, a tetracyclic, atypical antidepressant, was selected as a candidate for labelling with 11C for in vivo evaluation. (N‐methyl‐11C)Mianserin was produced by the alkylation of N‐desmethyl mianserin with (11C)methyl iodide followed by HPLC purification and formulation. (N‐methyl‐11C)Mianserin was obtained with a radiochemical purity >93% in a 16% decay corrected radiochemical yield. For a typical production starting with 40 GBq (11C)CO2, 1.9 GBq (N‐methyl‐11C)mianserin was obtained as a formulated solution in a synthesis time of 35 min (counted from EOB). Copyright © 2001 John Wiley & Sons, Ltd.

Shiue, Grace G.; Schirrmacher, Ralf; Shiue, Chyng‐Yann; Alavi, Abass A.

doi: 10.1002/jlcr.438pmid: N/A

Tolbutamide (1) and glyburide (7) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine‐18 labeled analogs, 1‐((4‐(18F)fluorobenzenesulfonyl))‐3‐butyl)urea (p‐(18F)fluorotolbutamide, 3a) and N‐{4‐(β‐(2‐(18F)fluoroethoxybenzene carboxamido)ethyl)benzenesulfonyl}‐N′‐cyclohexylurea (2‐(18F)fluoroethoxyglyburide, 6a) as β‐cell imaging agents. Compound 3a was synthesized via two approaches: One‐step synthesis via nucleophilic substitution of p‐nitrotolbutamide (2) with K(18F)/Kryptofix 2.2.2 in either CH3CN or DMSO gave a complicated mixture; a two‐step synthesis via preparation and reaction of 4‐(18F)fluorobenzenesulfonamide with butyl isocyanate in the presence of either copper (I) chloride or borontrifluoride etherate complex in CH3CN followed by HPLC purification yielded compound 3a in an overall yield of 1–2% with a synthesis time of 120 minutes from EOB. Compound 6a was synthesized by alkylation of the corresponding hydroxy precursor (5) with (18F)fluoroethyl tosylate in DMSO at 120°C for 20 minutes followed by HPLC purification in an overall yield of 5–10 % with a synthesis time of 100 minutes from Copyright © 2001 John Wiley & Sons, Ltd.

Oba, Makoto; Miyakawa, Akiko; Shionoya, Masanobu; Nishiyama, Kozaburo

doi: 10.1002/jlcr.439pmid: N/A

An asymmetric synthesis of regio‐ and stereoselectively deuterium‐labelled L‐isoleucine was examined. An unsaturated γ‐lactam readily available from L‐pyroglutamic acid was stereoselectively methylated by the Gilman reagent and subsequent oxidation of the hydroxymethyl moiety afforded a 3‐methylpyroglutamate derivative. Introduction of a deuterium atom into the γ‐position was achieved via a radical‐based deuteriation of the corresponding phenyl selenide by tributyltin deuteride. Then, the deuteriated 3‐methylpyroglutamate derivative was converted to L‐(4,5,5,5‐D4)isoleucine via a base‐promoted ring opening and a reductive deuteriation of the terminal carboxyl moiety. Copyright © 2001 John Wiley & Sons, Ltd.

Wiltshire, H R; Prior, K J; Dhesi, J; Maile, G

doi: 10.1002/jlcr.440pmid: N/A

The development of the collagenase inhibitor, cipemastat (Ro 32‐3555), required the synthesis of both carbon‐14 labelled and deuteriated material for the measurement of the parent drug and drug‐related material in biological fluids. In addition, labelled metabolites were needed for both in vitro metabolism and analytical studies. This paper describes the synthesis of labelled forms of cipemastat and its amide (Ro 32‐4778) and glucuronide (Ro 32‐6414) metabolites. Copyright © 2001 John Wiley & Sons, Ltd.

Taylor, George F.; Foarde, Karin K.; Webber, Tricia D.; Kepler, John A.

doi: 10.1002/jlcr.443pmid: N/A

(3‐3H)Propionic acid (1) was prepared by catalytic hydrogenation of 3‐bromo‐propionic acid with tritium gas. Fermentations of S. hygroscopicus were treated with 1 to produce (2a,8a,10a,14a‐3H)geldanamycin (2) with a specific activity of 76.2 mCi/mmol. The effect of the amount of 1 used and the dosing pattern on the specific activity of 2 was investigated. Copyright © 2001 John Wiley & Sons, Ltd.

Ellames, George J.; Herbert, John M.

doi: 10.1002/jlcr.447pmid: N/A

An efficient route is described for the preparation of (13C6)‐ϵ‐caprolactam (1b), and thence to (13C6)‐hexamethyleneimine (2b) hydrochloride. The sequence, from (13C6)‐phenol, uses a rhodium‐catalysed hydrogenation to generate labelled cyclohexanol, and thence cyclohexanone, whose oxime was subjected to a Beckmann rearrangement to give 1a. Copyright © 2001 John Wiley & Sons, Ltd.