Efficient synthesis and biological evaluation of epiceanothic acid and related compounds

✍ Scribed by Pu Zhang; Li Xu; Keduo Qian; Jun Liu; Luyong Zhang; Kuo-Hsiung Lee; Hongbin Sun

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 236 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.11.004

✦ Synopsis

Epiceanothic acid (1) is a naturally occurring, but very rare pentacyclic triterpene with a unique pentacyclic triterpene (PT) structure. An efficient synthesis of 1 starting from betulin (3) has been accomplished in 12-steps with a total yield of 10% in our study. Compound 1 and selected synthetic intermediates were further evaluated as anti-HIV-1 agents, inhibitors of glycogen phosphorylase (GP), and cytotoxic agents. Compound 1 exhibited moderate HIV-1 inhibition. Most importantly, compound 5, with an opened A-ring, showed significant GP inhibitory activity with an IC 50 of 0.21 lM, suggesting a potential for development as an anti-diabetic agent. On the other hand, compound 12, with a closed A-ring, showed potent cytotoxicity against A549 and MCF-7 human tumor cell lines, with IC 50 values of 0.89 and 0.33 lM, respectively. These results suggest that the A-ring of PTs is an important pharmacophore that could be modified to involve different biological activities.