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

Abstract

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