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: Liangfeng Fu, Gordon W Gribble
• Journal: Organic letters (Org Lett) Vol. 15 Issue 7 Pg. 1622-5 (Apr 05 2013) ISSN: 1523-7052 [Electronic] United States
• PMID: 23530743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Esters
• Oleanolic Acid
• bardoxolone methyl

Topics

• Anti-Inflammatory Agents (chemical synthesis, chemistry, pharmacology)
• Chromatography
• Diabetes Mellitus, Type 2 (drug therapy)
• Esters
• Humans
• Molecular Structure
• Oleanolic Acid (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Renal Insufficiency, Chronic (drug therapy)