Following the previously described semisynthetic preparation of new aglycones (8S)-8fluoroerythronolide A (I), (8S)-8-fluoroerythronolide B (II) and the monoglycoside 3-0mycarosyl-(8S)-8-fluoroerythronolide B (III), their conversion into new fluoroerythromycins was attempted by mutational biosynthesis. The strain Streptomyces erythraeus ATCC 31772, a mutant blocked in the biosynthesis of erythromycin, was employed in the present investigation. Four new antibiotics, (8S)-8-fluoroerythromycin A (IV), (8S)-8-fluoroerythromycin B (V), (8S)-8-fluoroerythromycin C (VI) and (8S)-8-fluoroerythromycin D (VII) were successfully derived by such an approach. The result is also discussed in terms of the substrate specificity of the enzymes involved in the biosynthesis of erythromycins. The new antibiotics exhibited promising biological properties. During the last twenty years advances in organic fluorine chemistry have been responsible for the development of a large number of new compounds of importance in biology and medicine. Replacement of an atom of hydrogen by one of fluorine in organic molecules may profoundly change their biological properties','). The rationale employed is that, since hydrogen and fluorine are nearly isosteric, the fluoro analog would be expected to have little difficulty in fitting onto active sites of receptors. At the same time, the strong electronegativity of the fluorine atom, when strategically placed, could be used to make defined alterations in the biological activity.

Basic derivatives of 6,7-dihydroindolo[1,7-ab][1]benzazepine and 6H-indolo[7,1-cd][1,5]benzoxazepine incorporating the imipramine basic side chain were synthesized and screened for antidepressant activity in mice. With few exceptions, the compounds unsubstituted at C-2 antagonized reserpine-induced ptosis and hypothermia showing negligible anticholinergic and antihistaminic properties. The compound 1-[2-(N-methyl-N-benzylamino)ethyl]-6,7-dihydroindolo[1,7-ab][1]benzazepine had the highest toxicity-activity ratio.

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Zu Untersuchungen auf entzündungshemmende Wirkung werden fluorierte Steroide hergestellt.

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