From Decades to Minutes. Steps Toward the Structure of Strychnine, 1910 – 1948, and the Application of Today’s Technology

Between 1910 and 1947, Robert Robinson (primarily) among others published numerous proposed structures for strychnine. Robinson published 17 of his strychnine papers with his doctoral advisor William Henry Perkin, Jr., though all but 2 appeared after Robinson had taken his first permanent academic position. This paper reports on and analyzes 20 key publications leading up to Robinson's (correct, then incorrect, then correct again though not definitive) proposal and Woodward's assignment of the actual structure of strychnine. We subjected the assignment of the strychnine structure to a modern computational quantum chemistry workflow. By computing, with density functional theory, 1H and 13C chemical shifts for the literature-proposed strychnine structures, we were able to rule out most incorrect structures. 13C NMR predictions were better at this, but 1H chemical shifts were helpful. A comparison is made between the consequences of publishing erroneous ideas in the first half of the 20th century and doing so in the 21st century.