| dc.description.abstract | Quinine is a naturally occurring plant alkaloid found in the bark of the Cinchona tree. Its medicinal relevance cannot be overstated as it is one of the most widely used anti-malarial drugs in the world. While the laboratory synthesis of quinine is not of practical value since this drug is easily extracted in large quantity from the natural source, the puzzle of designing reactions to create a route to stereochemically pure quinine has captivated synthetic chemists for generations. The purpose of this study is to prove the validity of a new route proposed by Stotter, Friedman, and Minter for the total synthesis of stereochemically pure quinine via a non-nitrogenous analog where the two nitrogen atoms of quinine are substituted with carbon atoms. The product of this model study is 1,1'-dideaza-quinine. Quinine is stereochemically complex with four separate stereocenters. Without control of stereochemistry, a non-selective synthesis of quinine could generate up to sixteen different isomeric structures. While the total synthesis of quinine with the correct stereochemistry was accomplished in 2001, the proposed route in our study will simplify the process by relying on a stereospecific aldol addition reaction to eliminate potential isomers. If successful, the results of this study will validate the concept of using the aldol as a key reaction to control the stereochemistry for three out of the four stereocenters in quinine. In addition, this synthetic route will demonstrate for the first time an approach to quinine that uses a convergent strategy rather than the linear strategy used by others who have investigated the total synthesis of this molecule. | |
