Synthesis of dammarane-type triterpenoids with anti-inflammatory activity in vivo

• Published in: Bioorganic & medicinal chemistry letters 2004-06, Vol.14 (11), p.2983-2986
• Main Authors: Scholz, Dieter, Baumann, Karl, Grassberger, Max, Wolff-Winiski, Barbara, Rihs, Grety, Walter, Hansrudolf, Meingassner, Josef G.
• Format: Article
• Language: English
• Subjects: Allergic contact dermatitis; Animals; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Dammar resin; Dammarane; Dammaranes; Dermatitis, Allergic Contact - drug therapy; Dermatitis, Allergic Contact - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Stability; Immunosuppressive; Immunosuppressive Agents - chemical synthesis; Immunosuppressive Agents - pharmacology; Medical sciences; Mice; Molecular Structure; Pharmacology. Drug treatments; Structure-Activity Relationship; Swine; Triterpene; Triterpenes - chemical synthesis; Triterpenes - pharmacology; Triterpenoids; Wittig
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.02.104

The synthesis and in vivo activity of new potent anti-inflammatory triterpenoids are described. The 17-α-substituted triterpene 1 [(17α)-23-( E)-dammara-20,23-diene-3β,25-diol] showed promising activity in animal models of immunosuppression and inflammation. Using a mouse model for inflammatory skin diseases (oxazolone-induced allergic contact dermatitis, ACD) as the directing in vivo test system, Structure–activity-relationship studies with the aim to understand the necessary structural requirements for the biological activity of 1 were conducted. Furthermore, we anticipated to identify biologically active compounds with the 17β configuration, which are thermodynamically more stable and much easier to synthesize. This was achieved by identifying the 17-β substituted dammarane 5 B and its analogues.