Toward a total synthesis of the immunosuppressant sanglifehrin A. Preparation of two relay compounds by degradation and their use in the reassembly of the natural product

A potential relay route for the synthesis of the novel immunosuppressive ag ent sanglifehrin A (1) has been developed. Degradation of 1 by a sequence i nvolving regioselective dihydroxylation of the C26,C27 double bond, followe d by periodate cleavage of the resulting diol 4, afforded lactol 2 and macr ocyclic aldehyde 3. Intramolecular ketal formation between the 1,3-diol and ketone functions present in 3 gave ketal-aldehyde 5. Lactol 2 was converte d into sulfone 14 in four steps. The fragments 5 and 14 were reassembled, u sing the Julia-Kocienski olefination procedure, to afford intermediate 15, which was converted back to sanglifehrin A (1) after two deprotection steps .