An Improved Synthesis of the HDAC Inhibitor Trichostatin A

Histone deacetylase inhibitors (HDIs) have found a wide variety of medicinal uses and are most noted for their specific apoptotic action towards cancer cells. Several hydroxamate HDIs have since been moved on to phase 1 and 2 clinical drug trials, with one having already been approved for treatment of advanced cutaneous T-cell lymphoma. Trichostatin A is one of the most potent known naturally-occurring inhibitors of histone deacetylase. Unfortunately for researchers, the syntheses that have been reported are both long and difficult, which leads to a low overall yield and therefore to a prohibitively expensive product, limiting its medicinal potential. This work builds on several previously published syntheses and shows a more efficient synthesis of Trichostatin A, which will make it more available for use in a variety of treatments.