Production Of Disubstituted Isoquinoline Derivatives: Steps Toward The Synthesis Of A Pratosine Analog

Abstract

The pyrrolophenanthridone alkaloid pratosine is a natural product related to hippadine, which is known to be a powerful but reversible inhibitor of spermatogenesis in rats. Hippadine has also shown cardiovascular as well as anticancer activity. Given the structural similarities between the two molecules, it is expected that pratosine will demonstrate biological activity similar to hippadine. Our work toward a laboratory synthesis of pratosine will facilitate large-scale production thus affording sufficient quantities of the material for a complete study of its pharmacological properties. Although we have a synthetic plan for preparing pratosine based on a model study, several reactions have failed due to solubility problems. This research focuses on using an alternate starting material with a large, lipophilic group to improve the solubility in ethereal solvents. The commercially available compound vanillin, which is extracted from vanilla beans, is a simple and inexpensive aldehyde with an appropriate structure for attaching the specific group(s) to be investigated. The goal is to find an extraneous substituent that will provide the required characteristics but which is sufficiently labile to be removed easily at the end of the synthesis.