FK506 immunosuppressant, synthesis

Studies on the exact mode of action of the unmodified sanglifehrin A (1) by Liu et al. found that 1 inhibits the T cell cycle (G1 phase), mediated by activation of the tumor suppressor gene p53 [21]. Sanglifehrin A (1) is a novel immunosuppressant, which, in addition to CsA, FK506, and rapamycin, represents a fourth class of immunophilin-binding metabolites with a new, as yet undefined mechanism of action [22]. The structural variation now accessible through total and partial synthesis should contribute to understanding of its bio-... 

Two reports of syntheses of the complex phosphine oxide (59) and its use in the synthesis of the C10-C34 fragment of FK506, a highly potent immunosuppressant macrolactam, have appeared.33,34... 

Curiously, the immunosuppressive activity of rapamycin (RAPA) does not involve the inhibition of IL-2 synthesis even though RAPA shares some structural similarities with FK506. The hF KB PI 2 RAPA complex interacts with a protein (RAFT in rat brain and FRAP in human) which controls the mRNA translation promoting the IL-2-stimulated Ga to S phase transition in T cells [6]. 

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