Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid

J Med Chem. 1990 Feb;33(2):833-8. doi: 10.1021/jm00164a057.


The syntheses and immunosuppressive bioassays of 12 side-chain variants of mycophenolic acid are described. The compounds were made either from mycophenolic acid itself or from 5-(chloromethyl)-1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisoben zofuran, a versatile intermediate for the synthesis of diverse side-chain variants. Replacement of the methylated E double bond of the natural product with a triple bond, a Z double bond, a saturated bond, or a sulfur atom, with overall chain lengths equal to or greater than that of mycophenolic acid, produced compounds devoid of significant activity. Replacement of the side-chain double bond with difluoro, dibromo, or unsubstituted cyclopropane rings also removed most activity. Replacement of the double bond with an allenic linkage yielded a compound with about one-fifth of the immunosuppressive activity of mycophenolic acid. Some possible causes for the unusual specificity of structure and activity are discussed.

MeSH terms

  • Animals
  • Antibody Formation / drug effects
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / pharmacology
  • In Vitro Techniques
  • Lymphocyte Activation / drug effects
  • Mice
  • Mitogens / pharmacology
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / chemical synthesis
  • Mycophenolic Acid / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / enzymology


  • Immunosuppressive Agents
  • Mitogens
  • IMP Dehydrogenase
  • Mycophenolic Acid