Journal of the American Chemical Society · 2003 · 116 citations · 32 references
PharmacyBiochemistryMedicinal ChemistryCarbohydrate ChemistryDrug DiscoverySynthetic Medicinal ChemistryCarbohydrate SynthesisGlycan BiosynthesisGlycosidic Bond FormationGlycosylation PathwaysMacrocycle SynthesisOligosaccharide AssemblyCarbohydrate SilylationCarbohydrate-derived Anticancer AgentsGlycoconjugate SynthesisGlycopeptide SynthesisGlycoside SynthesisGlycosidic Bond Cleavage PathwaysMacrolide GlycosidesNatural Product Total Synthesis
A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthesis calls for a dithiane coupling reaction to construct the C(20)-C(21) bond, a Stille coupling reaction to form the C(11)-C(12) bond, and a Yamaguchi macrolactonization to assemble the macrolide ring, as well as two glycosidation reactions to fuse the carbohydrate units onto the molecule. First and second generation syntheses to the required fragments for apoptolidin (1) are described.
32