ANALOGS OF THE MARINE IMMUNOSUPPRESSANT MICROCOLIN-A - PREPARATION AND BIOLOGICAL-ACTIVITY

A series of analogs of the immunosuppressive lipopeptide microcolin A has been prepared and evaluated for in vitro activity in the human and murine two-way mixed lymphocyte reaction. The compounds tested were o btained by semisynthetic modification and chemical degradation of the natural product. The relative potencies of these analogs suggest that the hydroxyproline and 5-methyl-3-pyrrolin-2-one portion of the molecu le are important for immunosuppressive activity and that other structu ral elements may play an ancillary role. Methanolysis of microcolin A also led to a novel immunosuppressive lactone analog.