A Total Synthesis of FK-5061
- 1 January 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (20), 6856-6872
- https://doi.org/10.1021/jo951646q
Abstract
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 α-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile α,β-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.Keywords
This publication has 21 references indexed in Scilit:
- Synthesis of the 9,10-acetonide of 9-dihydro-FK-506The Journal of Organic Chemistry, 1992
- Synthesis and analysis of 506BD, a high-affinity ligand for the immunophilin FKBPJournal of the American Chemical Society, 1991
- Total synthesis of FK506 and an FKBP probe reagent, [C(8),C(9)-13C2]-FK506Journal of the American Chemical Society, 1990
- Antineoplastic agents. 206. Structure of the cytostatic macrocyclic lactone combretastatin D-2The Journal of Organic Chemistry, 1990
- Studies directed towards the total synthesis of FK-506 preparation of a C(1) to C(15) segmentTetrahedron Letters, 1989
- Molecular recognition: hydrogen bonding and stacking interactions stabilize a model for nucleic acid structureJournal of the American Chemical Society, 1987
- Stereoselective reduction of .ALPHA.-methyl-.BETA.-hydroxy ketones with zinc borohydride.CHEMICAL & PHARMACEUTICAL BULLETIN, 1984
- Direct, regiospecific 2-lithiation of pyridines and pyridine 1-oxides with in situ electrophilic trappingThe Journal of Organic Chemistry, 1983
- Chemistry of cyclopropanes. I. Synthesis and deamination of spiroaminesThe Journal of Organic Chemistry, 1968
- Synthesis of a Macrocycle by Application of the Wittig ReactionThe Journal of Organic Chemistry, 1962