Synthesis of demethyl derivatives of istamycin A.
4-N,6'-N,3-O-Tridemethylistamycin A0 (9) and 6'N,3-O-didemethylistamycin A0 (15) were synthesized from 3,2',6'-tri-N-benzyloxycarbonyl-3',4'-dideoxyneamine 1,6-carbamate (1) through an aziridine derivative 6 by an analogous procedure employed in the total synthesis of istamycin A0 (19). Acylation of 15 with glycine at the 4-methylamino group gave 6'-N,3-O-didemethylistamycin A (18) having interesting activities especially against pseudomonas, but 4-N,6'-N,3-O-tridemethylistamycin A (12) derived from 9 showed only weak activity. Therefore, the 4-N-methyl group of istamycin A (20) is essential for the antimicrobial activity.
D000617:Aminoglycosides / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents; D001419:Bacteria / Q000187:drug effects; D004352:Drug Resistance, Microbial; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C022949:istamycins