R. Ireland, Longbin Liu, T. Roper
Sep 29, 1997
Citations
0
Influential Citations
18
Citations
Journal
Tetrahedron
Abstract
Abstract The C15C16 bond of FK-506 was formed via sulfone anion coupling followed by chelation controlled reduction of the C15 ketone. Efficient methylation of the C15-OH was accomplished by a combination of Me 3 OBF 4 -4A molecular sieves in the presence of Proton Sponge®. A procedure was developed to avoid epimerization at the C2 position of the pipecolinate section during alkaline hydrolysis. A reductive fragmentation of the C21–C24 [6,6]-spiroketal iodide using active Zn/Ag-graphite delivered the α′-allyl aldol section. The C9–C10 [5,6]-spiroketal acetonide was de-blocked via a novel β-elimination, using a combination of LiHMDS-Mg(HMDS) 2 in HMPA-DME (1:1), to afford an enediol acetal, which was oxidized with dimethyl dioxirane to generate the C8–C10 α, β-diketoamide acetal function. Final desilylations completed the total synthesis of FK-506.