Bioorganic & Medicinal Chemistry Letters 2011-01-01

Efficient synthesis and biological evaluation of epiceanothic acid and related compounds.

Pu Zhang, Li Xu, Keduo Qian, Jun Liu, Luyong Zhang, Kuo-Hsiung Lee, Hongbin Sun

Index: Bioorg. Med. Chem. Lett. 21 , 338-41, (2011)

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Abstract

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 μM, 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 μM, respectively. These results suggest that the A-ring of PTs is an important pharmacophore that could be modified to involve different biological activities.Copyright © 2010 Elsevier Ltd. All rights reserved.