An efficient synthesis of trichostatin A, a potent histone deacetylase inhibitor, was reported. The key point in this new approach lied in the highly stereocontrolled establishment of its chiral center using L-proline-catalyzed aldol reaction between p-nitrobenzaldehyde and propaldehyde. The aldol product was obtained with ＞99% ee and high de (anti∶syn＝16∶1). No racemization was found in the following process and the synthetic trichostatin A was a pure R enantiomer with more than 99% ee.

Key words: histone deacetylase inhibitor, L-proline, synthesis, trichostatin A