[Synthesis of bronchospasmolytically effective beta phenylethyl-aminoalkyl-xanthines]. / Synthesen von bronchospasmolytisch wirksamen beta-Phenläthyl-aminoalkyl-xanthinen

New theophylline and theobromine derivatives are synthetized from the beta-phenylethylaminoalkyl-xanthines, whose phenyl substituent is substitutent by one or two hydroxyl groups and partially also by other substituents. Different methods of synthesis are described, among them the production of the bronchospasmolytic 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol-HCl).

[Syntheses of 14C-1-erythro-norephedrine and its N-substitution products 14C-oxyfedrine and 14C-D 13,625]. / Synthesen von 14C-1-erythro-Norephedrin sowie seiner N-Substitutionsprodukte 14C-Oxyfedrin und 14C-D 13 625.

Starting from 14C-benzene (--)-erythro-norephedrine (14C-1-norephedrine) was obtained in a 6-step synthesis. 14C-1-Norephedrine functioned as an intermediate for the synthesis of the carbon labelled partial beta-agonist oxyfedrine hydrochloride (ildamen) and the new positive inotropic agent D 13 625 (alifedrine hydrochloride).

[Synthesis, absolute configuration and mass spectroscopic fragmentation of the circulation analeptic cafedrine (author's transl)]. / Synthese, absolute Konfiguration und massenspektroskopische Fragmentierung des kreislaufanaleptisch wirksamen Cafedrin.

The synthesis of [R-(R*,S*)]-7-[2-[(2-hydroxy-1-methyl-2-phenylethyl)amino]-ethyl]-3,7-dihydro-1 ,2-dimethyl-1H-purine-2,6-dione (Cafedrine) and its stereoisomers is reported. By means of 1H- and 13C-nmr spectroscopy the relative configuration of the two asymmetric centres is ascertained and the absolute configuration is discussed. The EI-mass spectrometric fragmentation of cafedrine has been elucidated.

[Studies on the biotransformation of reproterol. Structure determination of the main metabolite (author's transl)]. / Untersuchungen zur Biotransformation von Reproterol. Strukturaufklärung des Hauptmetaboliten.

Biotransformation of 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin), a beta 2-adrenergic drug recently introduced into therapeutic use, leads to the same main metabolite in animals and in man. By mass-spectroscopy and by synthesis its structure was shown to be tetrahydroisoquinoline derivative which is produced from reproterol by uptake of an additional carbon atom concomitant with cyclization.

[Structure-activity relationships of bronchospasmolytic beta-phenylethyl-aminoalkyl-xanthines (author's transl)]. / Struktur-Wirkungs-Beziehungen von bronchospasmolytisch wirksamen beta-Phenyläthyl-aminoalkyl-xanthinen

Structure-activity relationships of 90 bronchospasmolytic compenylethyl-aminoalkyl-xanthines are reported. Particularly the influence of substituents in the phenyl moiety as well as of the carbon bridge between the xanthine residue and the beta-phenylethylamine moiety is described. 2. A method is shown for the selection of one optimally bronchospasmolytic substance from many potential compounds synthetised via multiple screening steps to profound biological studies.

[Synthesis of radioactively labelled reproterol hydrochloride (author's transl)]. / Synthese von radioaktive markiertem Reproterol-hydrochlorid

Synthesis of radioactively labelled 7-(3-[2-(3,5-dihydroxy-phenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol) as needed for pharmacokinetic examinations, is described. The 14C-malonic diethyl ester was proven to be the suitable starting compound. The synthesis of the tritium-labelled reproterol is briefly described.