CHIMIA (Jul 1992)

Structure of Cyclosporine and Its Metabolites: Total Synthesis of Cyclosporine Metabolites Formed by Oxidation at Positions 4 and 9 of Cyclosporine. Preparation of Leucine-4-cyclosporine, (?-Hydroxy)-N-methyl-leucine-9-cyclosporine and Leucine-4-(?-hydroxy)-N-methyl-leucine-9-cyclosporine

  • Roland M. Wenger,
  • Kurt Martin,
  • Charles Timbers,
  • Anne Tromelin

Journal volume & issue
Vol. 46, no. 7-8

Abstract

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The syntheses of the cyclosporine metabolites Leu-4-cyclosporine (AM4N), (?-OH)MeLeu-9-cyciosporine (AM9) and Leu-4-(?-OH)MeLeu-cyclosporine (AM4N9) were completed. Aspartic acid was used as starting material to prepare peptides containing (?-OH)MeLeu residues. The structure of metabolite M13 was definitively established as being Leu-4-(?-OH)MeLeu-9-cyclosporine. The immunosuppressive activity in vitro of these synthesized metabolites was compared with that of cyclosporine and metabolite AMI.