Synthesis of derivatives of the novel cyclophilin-binding immunosuppressant sanglifehrin A with reduced numbers of polar functions

The syntheses and the biological activities of 53-deoxo sanglifehrin A (2) and 61-deoxy octahydrosanglifehrin A (3) are described. Compound 2 shows in tracellular cyclophilin (CyP)-binding and immunosuppressive activity in the mixed-lymphocyte reaction (MLR) similar to that of sanglifehrin A (1). Com pound 3 is much less active in the MLR despite unchanged intracellular CyP- binding. This indicates that the 53-keto group is not necessary for immunos uppressive activity, while the 61 hydroxy group is required. (C) 2001 Publi shed by Elsevier Science Ltd.