Peniphenones A–D from the Mangrove Fungus <i>Penicillium dipodomyicola</i> HN4-3A as Inhibitors of <i>Mycobacterium tuberculosis</i> Phosphatase MptpB

A pair of unusual benzannulated 6,6-spiroketal enantiomers [(−)-<b>1</b> and (+)-<b>1</b>] and three new biogenetically related compounds (<b>2</b>–<b>4</b>), together with two known related analogues (<b>5</b> and <b>6</b>), have been isolated from a mangrove fungus, <i>Penicillium dipodomyicola</i> HN4-3A. Their structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR data) and X-ray crystallography. The absolute configurations of enantiomers (−)-<b>1</b> and (+)-<b>1</b> were determined using quantum chemical calculations of the electronic circular dichroic (ECD) spectra. Compounds <b>2</b> and <b>3</b> exhibited strong inhibitory activity against <i>Mycobacterium tuberculosis</i> protein tyrosine phosphatase B (MptpB) with IC₅₀ values of 0.16 ± 0.02 and 1.37 ± 0.05 μM, respectively