synthesis of 2-deoxyfortimicins and 1-deamino-2-deoxy-2-epi-aminofortimicins via 2-O-methanesulfonylfortimicin B

J Antibiot (Tokyo). 1980 Aug;33(8):810-8. doi: 10.7164/antibiotics.33.810.

Abstract

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.

MeSH terms

  • Aminoglycosides / chemical synthesis*
  • Aminoglycosides / pharmacology
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Chemical Phenomena
  • Chemistry
  • Mass Spectrometry
  • Oxidation-Reduction

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • 1-deamino-2-deoxy-2 epi-aminofortimycin B
  • 2-deoxyfortimycin B
  • 2-O-methanesulfonylfortimycin B
  • 2-deoxyfortimycin A
  • 1-deamino-2-deoxy-2-epi-aminofortimycin A