Studies on an immunosuppressive macrolactam, ascomycin:
synthesis of a C-33 hydroxyl derivative.
Kawai M, Gunawardana IW, Mollison KW, Hsieh GC, Lane BC, Luly JR.
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL
Ascomycin 2, a close analogue of the immunosuppressant FK506 1, was modified to
incorporate a hydroxyl group at the C-33 position. This increased the aqueous
solubility of ascomycin by a hundred-fold at pH 7.4 and by approximately
300-fold at pH 6.5. Ascomycin 3 also exhibited an excellent immunosuppressive
activity in vitro, as tested in a human mixed lymphocyte proliferation (HuMLR)
assay, and in vivo using a rat popliteal lymph node (rPLN) hyperplasia assay.