An improved synthesis of 5,6-dimethylxanthenone-4-acetic acid (DMXAA)

Article abstract of DOI:10.1016/S0223-5234(02)01406-X

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a novel anticancer agent with a number of unique activities, and is in clinical trial. The current synthesis of DMXAA involves six steps, beginning with a heterogeneous reaction to form an isonitrosoacetanilide, and gives an overall yield of 11% from 2,3-dimethylaniline. We report an alternative synthesis of the key intermediate 3,4-dimethylanthranilic acid via nitration of 3,4-dimethylbenzoic acid and separation of the key desired isomer by ready crystallisation. This, together with improvements in the rest of the synthesis, provide a shorter and higher-yielding route to DMXAA (22% overall from 3,4-dimethylbenzoic acid).