Crystal structure of natural phaeosphaeride A

The asymmetric unit of the title compound, C15H23NO5, contains two independent molecules. Phaeosphaeride A contains two primary sections, an alkyl chain consisting of five C atoms and a cyclic system consisting of fused five- and six-membered rings with attached substituents. In the crystal, the molecules form layered structures. Nearly planar sheets, parallel to the (001) plane, form bilayers of two-dimensional hydrogen-bonded networks with the hydroxy groups located on the interior of the bilayer sheets. The network is constructed primarily of four O—H...O hydrogen bonds, which form a zigzag pattern in the (001) plane. The butyl chains interdigitate with the butyl chains on adjacent sheets. The crystal was twinned by a twofold rotation about the c axis, with refined major–minor occupancy fractions of 0.718 (6):0.282 (6)

4-Hydroxybenzyl Modification of the Highly Teratogenic Retinoid, 4-[(1<i>E</i>)-2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic Acid (TTNPB), Yields a Compound That Induces Apoptosis in Breast Cancer Cells and Shows Reduced Teratogenicity

Retinoids are a class of compounds with structural similarity to vitamin A. These compounds inhibit the proliferation of many cancer cell lines but have had limited medical application as they are often toxic at therapeutic levels. Efforts to synthesize retinoids with a greater therapeutic index have met with limited success. 4-[(1<i>E</i>)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB) is one of the most biologically active all-<i>trans</i>-retinoic acid (atRA) analogues and is highly teratogenic. In this study, we show that modification of the TTNPB carboxyl group with an <i>N</i>-(4-hydroxyphenyl)amido (4HPTTNPB) or a 4-hydroxybenzyl (4HBTTNPB) group changes the activity of the compound in cell culture and <i>in vivo</i>. Unlike TTNPB, both compounds induce apoptosis in cancer cells and bind poorly to the retinoic acid receptors (RARs). Like the similarly modified all-<i>trans</i>-retinoic acid (atRA) analogues <i>N</i>-(4-hydroxyphenyl)retinamide (4-HPR/fenretinide) and 4-hydroxybenzylretinone (4-HBR), 4HBTTNPB is a potent activator of components of the ER stress pathway. The amide-linked analogue, 4HPTTNPB, is less toxic to developing embryos than the parent TTNPB, and most significantly, the 4-hydroxybenzyl-modified compound (4HBTTNPB) that cannot be hydrolyzed <i>in vivo</i> to the parent TTNPB compound is nearly devoid of teratogenic liability