Structure and absolute stereochemistry of HIV-1 integrase inhibitor integric acid. A novel eremophilane sesquiterpenoid produced by a Xylaria sp.

Abstract

HIV-1 integrase is critical for viral replication and is absent in the host, and therefore is a potential target for the development of non-toxic antiviral therapy. From the screening of natural product libraries we have discovered integric acid, a novel eremophilane sesquiterpenoid, from a Xylaria sp. It inhibited 3′ -end processing, strand transfer and disintegration reactions catalyzed by HIV-1 integrase with IC 50 values of 3–10 μM. The isolation, structure elucidation, relative, and absolute stereochemistry of integric acid are described.