L. Christiaens

Synthesis of 2H,3-4-Dihydro-1,2-benzoselenazin-3-one and derivatives : A new heterocyclic ring system.

Abstract The synthesis of 2H-3,4-dihydro-1,2-benzoselenazin-3-ones which are six-membered homologues of Ebselen is described in order to evaluate their glutathione peroxidase-like activity. Spectral data of these new heterocycles are given.

A New Route for the Synthesis of [18f]Fluoroaromatic Substituted Amino Acids: No Carrier Added L-P-[18f]Fluorophenylalanine

L-p-[18F]fluorophenylalanine was designed as a potential marker for probing protein synthesis in the human brain by positron emission tomography. This radiotracer has been synthesized using nucleophilic displacement of the activated nitro group of p-nitrobenzaldehyde by NCA 18F- obtained from the 18O (p, n) reaction on enriched water. The L-form of the [18F]fluoroamino acid can be separated on an analytical scale chiral column. A typical production run of 22.2 GBq (600 mCi) of 18F obtained after a 10 microA.h bombardment of 18 MeV protons on 99.8% 18O-enriched water leads to a batch of 1.11 GBq (30 mCi) of NCA L-p-[18F]fluorophenylalanine after a total synthesis time of 120 min.

Synthesis of fluorine-18 substituted aromatic aldehydes and benzyl bromides, new intermediates for n.c.a. [18F]fluorination☆

The synthesis of various [18F]fluoroaromatic aldehydes using activated nitro precursors and amino-polyether supported nucleophilic substitution with 18F− is reported. These radiolabelled fluorinated aldehydes (radiochemical yields: 50–75%) are powerful key intermediates leading after treatment with NaBH4 and SOBr2 (SOCL2) to further active intermediates for example substituted [18F]fluorobenzyl bromides (yields 30–50% EOB). These benzaldehydes and bromides are particularly useful for the preparation of new radiopharmaceuticals (e.g. fluorotroprapride, fluorodexetimide) either by reductive amination or by aromatic N-alkylation. The preparation of various amino acids in D, L (50:50) or enriched L form by asymmetric synthesis is also possible (e.g. L-6-[18F]fluorodopa, L-4-[18F]fluoro-m-tyrosine). It can be anticipated that the 18F-labelled fluoroaldehydes will find widespread application in radiopharmaceutical chemistry.

ORTHOLITHIATION AS A TOOL FOR THE SYNTHESIS OF EBSELEN ANALOGUES

Abstract Ortholithiation reactions are shown to be effective tools for the synthesis of Ebselen (N-phenyl-benzisoselenazolin-3-one) derivatives.

The 1,3-benzotellurazole: a new heterocyclic system

Abstract We describe the synthesis of a new heterocyclic system : the 1,3-benzotellurazole, and some of its substituted derivatives.

Synthesis of monosulphur and monoselenium analogues of psoralen

Abstract The synthesis of new, highly efficient DNA photoinactivating agents comprising an atom of sulfur or selenium in place of oxygen in the psoralen system is described.

Nucleophilic enantioselective synthesis of 6-[18F]Fluoro-l-dopa via two chiral auxiliaries

Abstract Asymmetric nucleophilic synthesis of 6-[18F]fluoro- l -dopa was investigated in order to reach an enantiomeric excess of close to 100% of the l form of this amino acid. The radiochemical synthesis required [18F]fluoride as fluorinating agent and regioselective nucleophilic substitution of commercially available 6-nitroveratraldehyde. The [18F]fluorobenzaldehyde thus obtained was easily converted to the corresponding 2-[18F]fluoro-4,5-dimethoxybenzyl bromide. This alkylating agent was added to the lithium enolates of 1-(S)-(−)camphor imine of t-butyl glycinate (1) and (S)-(−)-1-Boc-2-t-butyl-3-methyl-4-imidazolidinone [(S)- Boc-BMI] (2) in order to compare the enantiomeric excess of the l form obtained in each case with these two chiral inductors. The l -isomer of fluorodopa was isolated after H1 hydrolysis and HPLC purification in 5–10% radiochemical yield (decay corrected). The overall synthesis time was of 110 min. Through this synthetic pathway, the l -isomer of fluorodopa was obtained in 83% e.e with 1 and 96% e.e with 2 respectively, as determined by chiral HPLC. A practical three step preparative scale synthesis of 6-[19F]fluoro- d,l -dopa is also presented.

An approach to the asymmetric synthesis of l-6-[18F]fluorodopa via NCA nucleophilic fluorination

Abstract The NCA asymmetric synthesis of l -6-[18F]fluorodopa starting from (1R,2R,5R)-[(+)-2-hydroxypinanyl- 3-idene]glycine t-butyl ester as chiral agent has been developed. After 18F-fluorination of the two commercially available aldehydes either 6-nitroveratraldehyde or 6-nitropiperonal, the required alkylating [18F]fluorobenzyl bromide derivative can be easily prepared by treatment with NaBH4 followed by SOBr2. Alkylation of the Schiff base was carried out with the lithium salt of 2,2,6,6-tetramethylpiperidine as base in anhydrous THF at −78°C. Following hydrolysis of the protecting groups with hydroxylamine and Hl, the l -amino acid was obtained in 75% l form (ee 50%) with a 10% decay corrected (120 min) radiochemical yield.

Direct electrochemical synthesis and crystal structure of tris(pyridine-2-selenolato)indium(III)

Abstract The compound [In(pySe)3] has been prepared byt he electrochemical oxidation of the metal in an acetonitrile solution of 2,2′-dipyridyl-diselenide [(pySe)2]. The crystal structures of 2,2′-dipyridyldiselenide and [In(pySe)3] have been determined by X-ray diffraction. Crystals of [(pySc)2] are orthorhombic, space group Pna21, with cell dimensions a = 17.499(2), b = 10.842(1) and c = 5.755(1) A . The indium compound has a molecular structure and its crystallizes in the monoclinic space group P21 with a = 8.754(3), b = 12.010(2), c = 9.403(3) A and β = 113.28(1)°. The indium atom has a distorted octahedral geometry with the ligand coordinated through both nitrogen and selenium atoms.

New synthesis of chalcogenochromones

Abstract We describe a new synthesis of chalcogenochromones and of some of their oxygen, sulfur, selenium and tellurium derivatives. The synthesis involves acidic cyclisation of ( o -alkylchalcogenophenyl) ethynyl ketones.