Aminoglycoside antibiotics. XIV. Synthesis and activity of 6-O-(3-amino-3-deoxy-alpha-D-glucopyranosyl)-and 5-O-(beta-D-ribofuranosyl)apramycins.

6-O-(3-Amino-3-deoxy-alpha-d-glucopyranosyl)apramycin (17) was prepared by glycosidation of a suitably blocked 5,6-dihydroxy derivative (11) of apramycin with a blocked 3-aminoglucosyl chloride (15). Ribosylation of the 5-hydroxy-6-O-tetrahydropyranyl (THP) derivative (19) of apramycin gave 5-O-(beta-d-ribofuranosyl)apramycin (24) along with the 6 alpha (25) and 6 beta (26) isomers. Similar reaction with the 6-hydroxy-5-O-THP derivative (20) or 11 gave only 25 and 26, but not 24. 17 was at least as active as apramycin against most Gram-positive and Gram-negative bacteria tested and more active than apramycin against most Gram-positive and Gram-negative bacteria tested and more active than apramycin against strains producing aminoglycoside-modifying enzymes. Strains of Pseudomonas aeruginosa were generally less sensitive to 17 than to apramycin. 24 was the most active of the three ribofuranosyl derivatives prepared though it was less active than 17.