The design and synthesis of novel steroid-derived inhibitors of hedgehog signaling based on the alkaloid cyclopamine

In Chapter 1, the discovery of the Shh pathway and its components is discussed. The isolation of cyclopamine, its biosynthesis and biological importance is presented as a culmination of work done by Keeler, Beachy et al. Cyclopamine has been shown to be an important compound in the fight against many cancers that utilize the Shh pathway to proliferate. However, cyclopamine faces many challenges. It is difficult to isolate and its synthesis is challenging. Cyclopamine also exhibits poor water solubility, and its treatment with dilute acid results in the formation of veratramine, a compound that causes hemolysis of the red blood cells.