The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a <i>Petrosia</i> sp. Marine Sponge Collected in Korea

Three new structurally related depsipeptides, halicylindramides F–H (<b>1</b>–<b>3</b>), and two known halicylindramides were isolated from a <i>Petrosia</i> sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F–H (<b>1</b>–<b>3</b>) were determined by Marfey’s method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (<b>2</b>) and H (<b>3</b>) were determined as 4<i>S</i> and 4<i>R</i>, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in <b>2</b> and <b>3</b> were speculated to both be 2<i>R</i> based on the shared biogenesis of the halicylindramides. Halicylindramides F (<b>1</b>), A (<b>4</b>), and C (<b>5</b>) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.