synthesis of 2-deoxyfortimicins and 1-deamino-2-deoxy-2-epi-aminofortimicins via 2-O-methanesulfonylfortimicin B.
The synthesis of 2-deoxyfortimicins A (15) and B (11) and 1-deamino-2-deoxy-2-epi-amino-fortimicins A (18) and B (12) is described. Two routes have been developed for synthesis of the key intermediate 2-O-methanesulfonylfortimicin B (7). One route involves selective blocking of fortimicin B with B-benzyloxycarbonyl groups followed by formation of a 4,5-salicylaldehyde oxazolidine derivative. Subsequent mesylation followed by deblocking gave 7. A more efficient route to 7 involves concomitant salicylaldehyde Schiff base and 4,5-oxazolidine formation followed by mesylation and hydrolysis. The formation of 1,2(R)-epiminofortimicin B (8) from 7 followed by RANEY nickel reduction gave 2-deoxyfortimicin B and 1-deamino-2-deoxy-2-epi-aminofortimicin B, which were converted to the corresponding fortimicin A derivative by selective N-blocking, N-acylation and subsequent deblocking. The antibacterial activities of the new fortimicin A derivatives are presented.
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D013058:Mass Spectrometry; D010084:Oxidation-Reduction
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C027413:1-deamino-2-deoxy-2 epi-aminofortimycin B; C027416:2-deoxyfortimycin B; C027414:2-O-methanesulfonylfortimycin B; C027415:2-deoxyfortimycin A; C027412:1-deamino-2-deoxy-2-epi-aminofortimycin A