ENZYMATIC-SYNTHESIS AND IMMUNOSUPPRESSIVE ACTIVITY OF NOVEL DESMETYLATED IMMUNOMYCINS (ASCOMYCINS)

31-O-Desmethylimmunomycin O: methyltransferase (DIMT), an enzyme invol ved in the biosynthesis of immunomycin (ascomycin/FR-900520), was used to synthesize three analogs of this immunosuppressant compound. These compounds were assigned the following structures: 13-O-desmethyl-, 15 -O-desmethyl- and 13,15-O-bisdesmethyl-immunomycins. Two of these comp ounds, namely, 15-O-desmethyl- and 13,15-O-bismethyl-immunomycins have novel structures and were examined for possible immunosuppressive act ivity by in vitro T-cell proliferation assay. The results showed that methylation of the C-15 hydroxyl is critical for full biological activ ity of the immunomycin.