Synthetic Studies toward the Natural Product Tripartin, the First Natural Histone Lysine Demethylase Inhibitor

Abstract

An efficient synthesis of dimethyl tripartin as a synthetic precursor of natural product tripartin, the first natural specific inhibitor of histone H3 lysine 9 demethylase KDM4, is described. The synthesis of dimethyl tripartin was achieved in a six-step longest linear sequence starting from commercially available 3,5-dimethoxy benzaldehyde with 21% overall yield, using ClTi(OiPr)3-mediated dichloromethine insertion as the key step.