Sporaricin B

The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.

Two new aminoglycoside antibiotics, sporaricins C and D have been isolated from the culture broth of Saccharopolyspora hirsuta subsp. kobensis, which produced sporaricins A and B. The structures of sporaricins C and D have been determined to be 4-N-carbamoyl-glycylsporaricin B and 4-N-formylglycylsporaricin B, respectively. Sporaricins C and D are active against Gram-negative and Gram-negative bacteria including aminoglycoside-resistant strains.

The novel, semisynthetic pseudodisaccharide antibiotic, 3-O-demethylsporaricin A, was synthesized via 3-O-demethylsporaricin B obtained by glycosidation of its aminocyclitol part. The aminocyclitol part was synthesized as D,L-form from D,L-(1,2,3/4,5,6)-1,4-bis(benzyloxy-carbonylamino)-5,6-O-isopropyl idene-2,3,5,6-cyclohexanetetraol via three key steps, namely, deoxygenation, inversion of a hydroxyl group, and N-methylation. The physical and biological properties of synthetic 3-O-demethylsporaricin A and an authentic sample derived from sporaricin B were identical.