Ludwig Macko

1,4,7-Triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA): a new bifunctional chelator for radio gallium-labelling of biomolecules

A new bifunctional chelator NODASA (1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) has been synthesised, its kinetically inert gallium(III) complex was crystallographically characterized and conjugated to a model aminoacidamide showing the feasibility of a prelabelling approach with 68,67Ga.

CHIRAL N-DIENYL-L-PYROGLUTAMIC ESTERS IN ASYMMETRIC HETERO-DIELS-ALDER REACTIONS WITH ACYLNITROSO DIENOPHILES

Abstract Asymmetric Diels-Alder reaction of the N-dienyl-L-pyroglutamic esters 1a-h with acyl nitroso dienophiles 4a-h gave diastereoisomeric adducts 6a-n, 7a-n with 12–90 % de, depending on solvents and temperature. An interpretation was gived. The “allylic effect” ( π C=C − σ ∗ N-C MO interactions) was found to be effective to account for the conformations of the adducts.

Stereoselective reactions of α-imide substituted radicals

Abstract The Barton esters 17 and 18, synthesized from the corresponding amino acid derivatives 6 and 14, were irradiated in situ with or without an external trap. Thus, thiopyridines 22 and 23, phenylselenides 24 and 25, esters 26 and 27 as well as deuterated products 34 and 35 were isolated when the radicals 20 and 21 were trapped with Barton esters 17 and 18 or with PhSeSePh, methyl acrylate or Bu3SnD. In all cases the anti isomers were isolated as the major products in moderate to excellent selectivity. The stereochemical course of the radical reactions can be explained by the allylic strain model.

In vivo and in vitro 27Al NMR studies of aluminum(III) chelates of triazacyclononane polycarboxylate ligands

The metallic radioisotope of a known radiopharmaceutical chelate, (67)Ga(NOTA) (NOTA=1,4,7-triazacyclonane-1,4,7-triacetic acid), used for tumor detection, was substituted by the chemically similar but non radioactive aluminum ion. Our aim was to detect and evaluate the in vivo behavior of the chelate. For this purpose, Al(NOTA) and the related chelate Al(NODASA) (NODASA=1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) were studied using in vitro and in vivo (27)Al NMR spectroscopy in rats. Both chelates showed high stability towards acid catalyzed dissociation and their (27)Al NMR resonances are characteristic of highly symmetrical species, with chemical shifts within the range for octahedral or pseudo-octahedral geometries. The thermodynamic stability constant of the novel chelate Al(NODASA) was estimated using (27)Al NMR. The value obtained suggested that the chelate does not undergo in vivo demetalation by transferrin. The in vivo spectroscopic studies and the analysis of blood and urine samples for Al(III) concentrations indicated that the chelates remain intact under physiological conditions and that they are mainly eliminated from the body through the kidneys.