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A Total Synthesis of FK-506 1

1996; American Chemical Society; Volume: 61; Issue: 20 Linguagem: Inglês

10.1021/jo951646q

1520-6904

Robert E. Ireland, James L. Gleason, Laura D. Gegnas, Thomas K. Highsmith,

Asymmetric Synthesis and Catalysis

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.