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.
Had they done it or not? That has been the question for decades. Woodward and Doering published the synthesis of d-quinotoxine in 1944. Based on the conversion of d-quinotoxine into quinine described by Rabe and Kindler in 1918, they claimed to have derived the total synthesis of quinine, though they had not actually completed this last step themselves before publishing. Their “formal” total synthesis was strongly challenged and was even dismissed as a “myth” by Gilbert Stork (Columbia University) in 2001.