Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Nelson, Andrew T.^1,2  Camelio, Andrew M.¹  Claussen, Karin R.¹  Cho, Jiyoon³  Tremmel, Lisa³  DiGiovanni, John³  Siegel, Dionicio^1,2 

[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA

[2] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA

[3] Univ Texas Austin, Coll Pharm, Dept Pharmacol & Toxicol, Austin, TX 78712 USA

关键词: Triterpene;    Cancer;    Mouse;    Skin inflammation;    Maslinic acid;    3-epi-Maslinic acid;    Corosolic acid;    3-epi-Corosolic acid;    Synthesis;    Natural product;    Chemoprevention;   

DOI  :  10.1016/j.bmcl.2015.07.029

来源: Elsevier

【 摘 要 】

The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized on the gram scale. Divergent diastereoselective reductions of a-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti-inflammatory activities as well as cancer chemopreventive activity. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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