Steps Towards the Synthesis of 1,1'-Dideaza-Quinine: A Proof of Concept

Weresh, Hank

Publication

Steps Towards the Synthesis of 1,1'-Dideaza-Quinine: A Proof of Concept

Weresh, Hank

Date

2021

Additional date(s)

2021-05-19

Abstract

Quinine is a naturally occurring alkaloid that is readily extracted from the bark of the Cinchona tree. It was the first chemical compound ever used to treat an infectious disease, malaria.1 Due to its structural complexity, organic chemists have been challenged to find efficient ways to synthesize pure quinine. The molecular structure of quinine contains four chiral centers which provide opportunity for 16 stereoisomers to exist. The development of a structured synthesis would open the door for biologically active analogs while also providing the chemistry community with reaction templates for controlling stereochemistry at chiral centers and limiting the formation of unwanted isomers. Additionally, since Cinchona trees are being uprooted to make way for large plantations2, a commercial synthesis for quinine may soon be necessary in our world's ongoing fight against malaria. Our group seeks to validate the model study proposed by Stotter, Friedman, and Minter11 through the production of a nitrogen-free, quinine analog. Our synthesis follows a convergent approach thanks to a tandem aldol addition-reduction step that establishes two of the four chiral centers in one process. This paper focuses on the optimization and standardization of the synthetic procedures used to produce the precursors involved in this marquee step.