A TOTAL SYNTHESIS OF FK-506

A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top a nd bottom half sections of the molecule are coupled by addition of a v inyl 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 b y a late stage generation and oxidation of a masked enediol. Top and b ottom half segments are themselves derived by coupling of smaller subu nits, resulting in a very convergent route.