Structure of sisomicin, a novel unsaturated aminocyclitol antibiotic from Micromonospora inyoensis

Abstract

Sisomicin, the principal antibiotic produced in the fermentation of Micromonospora inyoensis, has been shown to be 0-2,6-diamino-2,3,4,6-tetradeoxy-a-D-gZycero-hex-4-enopyranosyl(l-4)-0-[3-deoxy-4-C-methyl-3-(methylamino)-/?-L-arabinopyranosyl(l-6)]-2-deoxy-D-streptamine (1). Sisomicin contains a novel unsaturated sugar unit, not previously encountered in any aminocyclitol antibiotic.Submerged fermentations of Micromonospora inyoensis (NRRL 3292) produce sisomicin,1 a novel unsaturated aminocyclitol antibiotic2•3 having broad spectrum antibacterial activity.4 Sisomicin is the major component of the crude antibiotic complex, which was isolated from the fermentation broth by ion-exchange chromatography.3 Column chromatography of the crude antibiotic on silica Preparative Routes to 4-Amino-4-deoxy-D-galactose1

Antibiotics in the clinical pipeline at the end of 2015

“…19) (ACHN-490)134,135 is a semi-synthetic derivative136 of the aminoglycoside sisomicin137,138 that has broad-spectrum activity against both G+ve and G − ve bacteria [139][140][141][142]. is being evaluated by Achaogen, Inc. (South San Francisco, CA, USA) in phase-III trials for the treatment of cUTI and pyelonephritis (NCT02486627) and carbapenem-resistant Enterobacteriaceae VAP, HAP and bloodstream infections (NCT01970371).…”

Enzymatic Modification of Aminoglycoside Antibiotics: a New 6′- N -Acetylating Enzyme from a Pseudomonas aeruginosa Isolate

“…The acetylated product from P. aeruginosa 3796 must, therefore, be 6'-N-acetylsisomicin (1). The assignment is supported by the position of the 6'-methylene resonance of (1) at 8 3.73 ppm, 0.61 ppm downfield from the analogous resonance in sisomicin (8).…”

“…3, ion A material, which corresponds to ion B (Fig. 3) and is unshifted from its position in sisomicin (8). The acetylated product from P. aeruginosa 3796 must, therefore, be 6'-N-acetylsisomicin (1).…”

Aminoglycoside Antibiotics

“…10.4) which differ from the kanamycins and tobramycin in their ring III aminosugar (Cooper 1971). In contrast, the sisomicin group contains an uncommon unsaturated sugar moiety at that position (Reimann et al 1974). The three-component gentamicin complex pioneered the medical success of the aminoglycoside class and established its clinical utility for treating Gram-negative bacteria and other susceptible pathogens.…”