Total Synthesis of Quinine by Woodward, Williams
Woodward/Doering quinine synthesis part III:
The first major synthesis by Woodward after quinine was that of the steroid nucleus, including cholesterol (1951) and cortisone (1951). Woodward went to the United Kingdom in 1951 to deliver a Centenary Lecture. He spoke about
The Woodward-Doering/Rabe-Kindler total synthesis …
En route to quinine
Woodward and William von Eggers Doering make headlines when they publish what today would be called a formal synthesis of the antimalarial drug quinine.
that Woodward and Doering’s synthesis was not a …
Drugs derived from cinchona bark, known as cinchona alkaloids, have been used in healing from ancient times. The most prominent representative of this group is quinine, a bitter substance contained in beverages such as tonic water and used in modern medicine to combat malaria. As early as 1945, Robert Burns Woodward and William von Eggers Doering (Harvard University) described how to synthesize quinine in the laboratory. The last step of this "formal" total synthesis, a three-step reaction procedure previously described by Paul Rabe and Karl Kindler in 1918, has continued to be the subject of much controversy to this day. Aaron C. Smith and Robert M. Williams at Colorado State University (USA) have now successfully reproduced the Rabe-Kindler protocol. As described in an Angewandte Chemie article dedicated to Doering on his 90th birthday, they repeated the entire procedure without employing any modern methods.
the Woodward-Doering-Rabe-Kindler total synthesis of ..
In 1944, with his student William von Doering, Woodward completed the synthesis of the , used to treat . Although the synthesis was publicized as a breakthrough in procuring the hard to get medicinal compound from Japanese occupied southeast Asia, in reality it was too long and tedious to adopt on a practical scale. Nevertheless it was a landmark for chemical synthesis. Woodward's particular insight in this synthesis was to realise that the German chemist Paul Rabe had converted a precursor of quinine called quinotoxine to quinine in 1905. Hence, a synthesis of quinotoxine (which Woodward actually synthesized)) would be tantamount to synthesizing quinine. When Woodward accomplished this feat, organic synthesis was still largely a matter of trial and error, and nobody thought that such complex structures could actually be constructed. Woodward showed that organic synthesis could be made into a rational science, and that synthesis could be aided by well-established principles of reactivity and structure. This synthesis was the first one in a series of exceedingly complicated and elegant syntheses that he would undertake.