title: An improved synthesis of 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
abstract: 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).
authors.affiliation: Auckland Cancer Society Research Centre, School of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1000, New Zealand.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Atwell
authors.forename: Shangjin
authors.initials: S
authors.lastname: Yang
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D003460:Crystallization; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009566:Nitrates / Q000737:chemistry; D014966:Xanthenes / Q000138:chemical synthesis* / Q000302:isolation & purification; D044004:Xanthones; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009566:Nitrates; D014966:Xanthenes; D044004:Xanthones; D062367:ortho-Aminobenzoates; C066668:vadimezan; C031385:anthranilic acid