Principal Investigator: David Lewis
Abstract: DESCRIPTION: (Principal Investigator's Abstract) In 1991 and 1992, patents were issued in the United States and in Great Britain for the use of certain C19 diterpenoid alkaloids for both the treatment of narcotic addiction and for alleviation of symptoms arising from the withdrawal syndrome encountered with opiate addicts. Due to their non-narcotic nature, these compounds may offer considerable promise for impacting favorably on the limitations of contemporary maintenance programs which remain centered around the controlled administration of substitute narcotics such as methadone. The long-term goal for the research proposed herein is to develop a new strategy for the total synthesis of these alkaloids which could make synthetic compounds to be readily available to support laboratory investigation and controlled pre-clinical pharmacological studies of their antinociceptive activity for treating narcotic addiction. It is expected that this long-term goal will be addressed in five stages. This proposal will explicitly address the first stage. Its specific aim is to develop one or more efficient routes for the total synthesis of a simple tetracyclic ABEF synthon to demonstrate the feasibility of the key early cyclization steps of the proposed overall synthetic strategy. ln the proposed work, the synthesis of the tetracyclic synthon will be carried out by sequential intramolecular phenoxy radical coupling, Michael addition and aldol addition reactions.
Funding Period: 2001-03-01 - 2004-02-28
more information: NIH RePORT