A Total Synthesis of FK-506(1).
A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top and bottom half sections of the molecule are coupled by addition of a vinyl cuprate with a spiroenone. The alpha-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile alpha,beta-diketoamide hemiketal portion of the molecule is prepared by a late stage generation and oxidation of a masked enediol. Top and bottom half segments are themselves derived by coupling of smaller subunits, resulting in a very convergent route.
Ireland
Robert E.
RE
Department of Chemistry, McCormick Road, University of Virginia, Charlottesville, Virginia 22901.
Gleason
James L.
JL
Gegnas
Laura D.
LD
Highsmith
Thomas K.
TK