Concise, convergent syntheses of (±)-trichostatin A utilizing a Pd-catalyzed ketone enolate α-alkenylation reaction
Casey C Cosner1, Paul Helquist
1251 Nieuwland Science Hall, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
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.
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