Dihydro‐ β ‐agarofurans from the Australian Endemic Rainforest Plant Denhamia pittosporoides Inhibit Leucine Transport in Prostate Cancer Cells

Two previously unknown dihydro‐ β ‐agarofuran sesquiterpenoids, denhaminol I ( 1 ) and denhaminol J ( 2 ), together with four related and known metabolites, 1 α ,2 α ,6 β ,15‐tetraacetoxy‐9 α ‐benzoyloxy‐8‐oxodihydro‐ β ‐agarofuran ( 3 ), wilforsinine F ( 4 ), 1 α ,2 α ,6 β ,8 α ,15‐pentaacetoxy‐9 α ‐benzoyloxydihydro‐ β ‐agarofuran ( 5 ), and 1 α ,2 α ,6 β ,15‐tetraacetoxy‐9 β ‐benzoyloxydihydro‐ β ‐agarofuran ( 6 ), were isolated from the leaves of an Australian rainforest plant, Denhamia pittosporoides . The structures of compounds 1 and 2 were determined by analysis of their 1D/2D NMR and MS data. The absolute configuration of compound 1 was established by single‐crystal X‐ray diffraction analysis. Compounds 1 and 4 were shown to inhibit leucine transport in the human prostate cancer cell line LNCaP, with IC 50 values of 51.5 and 95.5 μ m , respectively. Both compounds 1 and 4 were more potent than the l ‐type amino acid transporter (LAT) family inhibitor 2‐aminobicyclo[2.2.1]‐heptane‐2‐carboxylic acid (BCH). This is the first report of dihydro‐ β ‐agarofurans from D. pittosporoides .