title: Efficient and scalable synthesis of bardoxolone methyl (cddo-methyl ester).
abstract: Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ∼50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States.
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Fu
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Gribble
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002845:Chromatography; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004952:Esters; D006801:Humans; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D004952:Esters; D009828:Oleanolic Acid; C445068:bardoxolone methyl