Tetracyclic Steroids Bearing a Bicyclo[4.4.1] Ring System as Potent Antiosteoporosis Agents from the Deep-Sea-Derived Fungus <i>Rhizopus</i> sp. W23

Abstract

Chemical investigation of the deep-sea-derived fungus <i>Rhizopus</i> sp. W23 resulted in the identification of six new (<b>1</b>-<b>3</b>, <b>6</b>, <b>8</b>, <b>9</b>) and 12 known (<b>4</b>, <b>5</b>, <b>10</b>-<b>19</b>) cyclocitrinol analogues, together with one handling artifact (<b>7</b>), all featuring an unusual 7/7/6/5-tetracyclic scaffold and bicyclo[4.4.1] A/B rings. Norcyclocitrinoic acids A and B (<b>1</b>, <b>2</b>) represent the second occurrence of 24,25-bisnor cyclocitrinols. Structures were assigned to new steroids on the basis of extensive spectroscopic analysis and X-ray crystallography. Compound <b>13</b> significantly enhances osteoblastogenesis and inhibits adipogenesis in mature bone marrow stromal cells at 5 μM, indicating a potential to be an antiosteoporosis lead.