title: Concise, convergent syntheses of (±)-trichostatin A utilizing a Pd-catalyzed ketone enolate α-alkenylation reaction.
abstract: Two concise, convergent syntheses of (±)-trichostatin A (1), a potent histone deacetylase inhibitor, have been accomplished. The key step in both is a Pd-catalyzed α-alkenylation reaction between ketone 2 and either dienyl bromide 3 or alkenyl bromide 9 using a modification of cross-coupling conditions described by Negishi and Hartwig. A brief investigation has shown the potential utility of a Ni-catalyzed version of this reaction. The overall synthetic routes are short and amenable to scaleup, providing access to trichostatin A via trichostatic acid as a direct precursor.
authors.affiliation: 251 Nieuwland Science Hall, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Cosner
authors.forename: Paul
authors.initials: P
authors.lastname: Helquist
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D005231:Fatty Acids, Unsaturated; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007659:Ketones; C066131:trichostatic acid; C012589:trichostatin A; D010165:Palladium