SANNAMYCIN-TYPE AMINOGLYCOSIDE ANTIBIOTICS OF NATURAL AND NONNATURAL (MIRROR-IMAGE) CONFIGURATION - TOTAL SYNTHESES AND BIOLOGICAL-ACTIVITY

Sets of variously protected purpurosamine/2-epi-purpurosamine-type gly cosyl donors (O-acetates) and sannamine-type glycosyl accepters were c oupled as racemates and pure enantiomers, according to a modified Koen igs-Knorr procedure with TMSOTf as promotor. The alpha anomers isolate d from the respective mixtures of glycosides (yields varying between 5 1% and 91%, alpha:beta anomeric ratios between 1.5:1 and 13:1, alpha:a lpha diastereomeric ratios between 1:1 and 1:1.5) were transformed thr ough standard protection/deprotection and glycidation measures into 6' -des(N-methyl)sannamycins A (1, 1', 2, 2') and B (37, 37'), 2'-epi-6'- des(N-methyl)sannamycins (3, 3'), the enantiomeric sannamycins A and B (ent-4)/(ent-40), the diastereomers (ent-4')/(ent-beta-5), and the en antiomeric 2'-epi-sannamycin A (ent-5)/(ent-beta-5). For one of the fl uorinated glycosides (alpha-26'), featuring a somewhat unusual aglycon conformation, an X-ray structural analysis was performed. In explorat ive biological tests, the naturally configurated glycosides 1 and 3 sh owed limited, 2 a rather broad activity against a number of pathogenic microorganisms. Yet, none of the glycosides with non-natural configur ation was found to be active.