Role of the 1-amino group in aminocyclitol antibiotics: synthesis of 1-deaminogentamicin C2.
The synthesis of 1-deaminogentamicin C2 described here, uses 3,2',6',3"-tetrakis-N-tert-butoxycarbonylgentamicin C2 (2) as intermediate. N-Formylation of 2 followed by per-O-acetylation and dehydration furnished the isocyanide 5. Radical-induced deamination of the latter using tri-n-butylstannane and removal of the protecting groups afforded the target 1-deaminogentamicin C2 (7). Its in vitro antibacterial activity is less than that of the parent gentamicin C2. The behaviour of 7 towards aminoglycoside-inactivating enzymes was also examined; interestingly, it was found to be neither substrate nor inhibitor for such enzymes. These results strongly suggest that the substitution pattern of the 1-position determines the biological properties of the aminoglycoside antibiotics.
D005839:Gentamicins / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D005839:Gentamicins; C037745:1-deaminogentamicin C2