Structural elucidation of A-74528, an inhibitor for 2′,5′-phosphodiesterase isolated from Streptomyces sp.

A-74528 (1) is a metabolite of Streptomyces sp. discovered in the screening for 2′,5′-oligoadenylate phosphodiesterase inhibitors. The planar structure of 1 was mainly elucidated by NMR techniques including natural abundance INADEQUATE, and the relative configuration and the conformation were elucidated by the analyses of NOEs and assessment of dihedral angles predicted by QUANTA/CHARMm computations and coupling constants. It was proved that 1 is a highly fused polyketide with a side-chain branching site that never appeared before from the nature.