title: Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties.
abstract: 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 α-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.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States; Department of Chemistry, University of Texas at Austin, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Nelson
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Camelio
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Karin R
authors.initials: KR
authors.lastname: Claussen
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, United States.
authors.forename: Jiyoon
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tremmel
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, United States.
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States; Department of Chemistry, University of Texas at Austin, United States.
authors.forename: Dionicio
authors.initials: D
authors.lastname: Siegel
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000737:chemistry*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D009828:Oleanolic Acid; D010100:Oxygen; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: 3-epi-Corosolic acid; 3-epi-Maslinic acid; Cancer; Chemoprevention; Corosolic acid; Maslinic acid; Mouse; Natural product; Skin inflammation; Synthesis; Triterpene